Role of 18F-FDG-PET/CT in establishing new clinical and therapeutic modalities in lung cancer. A short review | Revista Española de Medicina Nuclear e Imagen Molecular (English Edition)

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(A) Delayed planar images in anterior (left) and posterior (right) projections showing an increased uptake in the left glenoid region (arrow), compatible with prosthetic loosening. A mild focal uptake is barely seen in the middle third of the left humerus (head arrow). (B) SPECT/CT images (from up to down: CT, SPECT and fusion images; from left to right: coronal, sagittal and axial views) are consistent with mechanical loosening of the glenoid component (arrows). (C) Details of coronal (left) and axial (right) views of the fusion SPECT/CT images, localizing the mild humeral uptake previously described on the medial side of the cortical bone of the left humeral diaphysis (arrows), far from the stem tip (head arrow), suggesting a stress lesion, and therefore discarding a loosening of the humeral prosthetic component." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J.P. Suárez, M.L. Domínguez, N. Zeidán, M.E. García, D. Lisei, N. Martín, F.M. 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A short review" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "229" "paginaFinal" => "233" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Roberto C. Delgado Bolton, Adriana K. Calapaquí-Terán, Francesco Giammarile, Domenico Rubello" "autores" => array:4 [ 0 => array:3 [ "nombre" => "Roberto C." "apellidos" => "Delgado Bolton" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Adriana K." 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Una breve revisión" ] ] "textoCompleto" => "IntroductionNon-small cell lung cancer (NSCLC) represents 85%–90% of all lung cancers.<a class="elsevierStyleCrossRef" href="#bib0310">1</a> It includes three main sub-types: (a) squamous-cell carcinoma, (b) adenocarcinoma, and (c) large-cell carcinoma. The first two sub-types account for about 80% of all lung cancers worldwide. NSCLC is predominantly associated with smoking and usually present as large tumours in the centre of the lung.<a class="elsevierStyleCrossRefs" href="#bib0315">2,3</a> In contrast, adenocarcinomas are frequently located in the peripheral areas of the lungs, and are divided into the following subtypes: (a) acinar, (b) papillary, (c) bronchiolo-alveolar carcinoma (BAC), and (d) solid adenocarcinoma with relevant mucin production. In non-smokers, the most frequent type of lung cancer is the adenocarcinoma.<a class="elsevierStyleCrossRef" href="#bib0325">4</a> Mixed histologic patterns are present in many cases.18F-FDG PET/CT in the diagnosis and staging of NSCLCThe imaging diagnostic work-up of patients with lung NSCLC includes chest X-ray, contrast-enhanced CT (ceCT), bone scintigraphy, and more recently 18F-FDG PET/CT and, in bronchial neuroendocrine tumours (NET) 111In planar and SPECT somatostatin receptor scintigraphy (SRS), which has been recently substituted by PET/CT with 68Ga-DOTA-peptides mainly DOTA-TOC, DOTA-NOC, DOTA-TATE.<a class="elsevierStyleCrossRef" href="#bib0330">5</a>In this context, ceCT has been the gold standard imaging technique for many decades, and still maintains a pivotal role in evaluating the primary tumour features (morphology, inhomogeneity, shape, irregular margins and so forth) as well as the connections with the surrounding structures, especially the mediastinum and pleura. ceCT major limitation is related to the fact that it relies exclusively on morphological aspects, while 18F-FDG and 68Ga-DOTA-peptides using hybrid PET/CT scanners are able to provide both metabolic and accurate anatomic information in a single exam.<a class="elsevierStyleCrossRefs" href="#bib0310">1,6</a>As reported before, 18F-FDG is the most commonly used PET tracer.18F-FDG PET/CT has been extensively studied in lung cancer. There is large evidence in literature showing its utility in: (a) characterising benign versus malignant solitary pulmonary nodules,<a class="elsevierStyleCrossRefs" href="#bib0310">1,4</a> (b) in the staging and re-staging of lung cancer,<a class="elsevierStyleCrossRefs" href="#bib0310">1,4,6,7</a> (c) guiding surgical, chemo- and/or radiotherapy treatments,<a class="elsevierStyleCrossRefs" href="#bib0340">7,8</a> (d) monitoring treatment response<a class="elsevierStyleCrossRefs" href="#bib0310">1,7-9</a> and (e) predicting outcome of lung cancer.<a class="elsevierStyleCrossRefs" href="#bib0310">1,8,9</a> Some of these indications are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Furthermore, 18F-FDG PET/CT has demonstrated its utility from a cost-effectiveness point of view compared to thoracoscopy and surgery when systematically performed in all patients with a lung nodule of uncertain origin.<a class="elsevierStyleCrossRef" href="#bib0355">10</a> As a consequence of the building evidence in favour of PET/CT in lung cancer, it has been progressively included in guidelines and consensus documents.<a class="elsevierStyleCrossRefs" href="#bib0310">1,5,11,12</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>FDG PET/CT in restaging loco-regional recurrenceAs a whole, mainly depending from the hystologic subtipes and TNM, lung cancer relapses after primary treatment in 30%–75% of patients.<a class="elsevierStyleCrossRefs" href="#bib0315">2,3</a> As in other cancers, after initial treatment (surgery, chemio-radiotherapy), differentiating local-regional recurrence from post-surgical non-tumoral changes as athelectasis, pharenchima consolidations, and radiation-induced fibrosis, may be difficult when using ceCT alone.<a class="elsevierStyleCrossRefs" href="#bib0310">1,4</a> In this regard, a great help derives from 18F-FDG PET/CT which has the great advantage of evidencing areas with high 18F-FDG uptake by metabolically active tissues, suggestive of cancer remnant/recurrence, thus providing relevant information for planning subsequent therapies.<a class="elsevierStyleCrossRefs" href="#bib0310">1,4,11-14</a>It should be kept in mind that recent radiotherapy may provide false positive results related to inflammation. To solve this problem, a PET/CT control is performed two or three months after the end of radiotherapy, when 18F-FDG-inflammatory uptake typically decreases to very low or absent values, therefore excluding persistent/recurrent tumour.<a class="elsevierStyleCrossRefs" href="#bib0310">1,8,10</a> However, the positive results due to active inflammation, are now being used in the diagnosis of infection and inflammation demonstrating a good diagnostic performance, such as cases of infective endocarditis or vasculitis.<a class="elsevierStyleCrossRefs" href="#bib0380">15-18</a> On the other hand a PET/CT control performed close to chemotherapy may give a false negative result: so it is recommended in clinical practice to allow for a time interval longer than 1 month to perform a PET/CT after the end of chemotherapy.<a class="elsevierStyleCrossRefs" href="#bib0310">1,3,4,8</a>Recurrence of NSCLC may be classified as loco-regional relapse or distant metastatic spread, the latter being the most common form of NSCLC recurrence. Depending on the initial stage at diagnosis and on the treatment applied, metastatic recurrence comprehends 39%–65.5% of cases, whereas the remaining 30% are limited and defined as loco-regional recurrence.<a class="elsevierStyleCrossRefs" href="#bib0310">1,2, 4</a>Yet, loco-regional recurrence is typically located within the treated hemithorax, usually presenting as nodules that involve the surgically treated area or the area treated by radiofrequency or microwave ablation, and in other ipsilateral thoracic structures (bronchial stump, pleura, chest wall, and lymph nodes).<a class="elsevierStyleCrossRefs" href="#bib0310">1,4,19</a>Lastly, apart from recurrences, new primary lung cancer is reported in 1%–2% of NSCLC patients per year after initial radical therapy.<a class="elsevierStyleCrossRef" href="#bib0405">20</a>PET/CT in cancer restaging after surgery aloneThe study by Toba et al.<a class="elsevierStyleCrossRef" href="#bib0410">21</a> retrospectively included 101 NSCLC patients who had undergone potentially curable operations and were followed by an 18F-FDG PET/CT controls every subsequent year (for a total of 233 18F-FDG PET/CT studies), in order to select patients without clinical or radiological evidence of recurrence. Of relevance, eighteen (18%) asymptomatic patients had recurrent disease and 22 recurrent sites were confirmed: 18F-FDG PET/CT correctly diagnosed recurrence in 17 of the 18 (94%) patients and 21 of the 22 (95%) recurrent sites. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 94.4, 97.6, 89.5, 98.8 and 97.0, respectively.Another study by Choi et al. analysed the performance of 18F-FDG PET/CT for detecting recurrent disease after initial intent curative surgery.<a class="elsevierStyleCrossRef" href="#bib0415">22</a> They included a large series of 358 patients who had undergone complete resection of NSCLC and that then were followed-up with 18F-FDG PET/CT and other conventional imaging methods (ceCT, bone scan). Recurrent disease occurred in 31% of patients: recurrence disease was detected both with ceCT and 18F-FDG PET/CT in 51% of patients and only by 18F-FDG PET/CT in 37% of cases. 18F-FDG PET/CT was false negative in 6 small or hypometabolic recurrent lesions. Because of this, the authors recommended an annual screening method including both 18F-FDG PET/CT and a chest ceCT.PET/CT after surgery & chemotherapy, chemo-radiotherapy or radiotherapy aloneA meta-analysis evaluated the diagnostic efficacy of PET and PET/CT with 18F-FDG compared to conventional imaging (CI) techniques (ceCT, bone scan) for the detection of recurrent lung cancer.<a class="elsevierStyleCrossRef" href="#bib0400">19</a> Thirteen articles and 1,035 patients were included. Pooled sensitivity for PET, PET/CT, and CI were 0.94, 0.90, and 0.78, respectively. Pooled specificity for PET, PET/CT, and CI were 0.84, 0.90, and 0.80, respectively. With regards to sensitivity, lower values were associated with CI than PET (p=0.000) and PET/CT (p=0.005), and there was no significant difference between PET/CT and PET (p=0.1). Regarding specificity, values for PET/CT and PET were significantly higher than CI (both p=0.000), with no significant difference between PET/CT and PET (p=0.2). The analysis with SROC curves evidenced a better diagnostic accuracy associated with PET/CT than PET and CI. They concluded that PET/CT and PET were superior imaging modalities for the detection of recurrent lung cancer.Other studies not included in the above mentioned systematic review and meta-analysis also found that PET/CT was associated with high specificity for the detection of recurrent disease following initial treatments, including homogeneous patient populations treated with surgery, radiotherapy, or radiofrequency ablation. These therapeutic modalities are discussed below in the text.PET/CT after stereotactic body radiation therapy (SBRT)Stereotactic body radiation therapy (SBRT) is an established treatment option for early-stage lung cancer. SBRT causes focal changes in the lung parenchyma close to the tumour site, most frequently represented by a ground glass opacity (GGO).<a class="elsevierStyleCrossRef" href="#bib0310">1</a>The study by Pastis et al.<a class="elsevierStyleCrossRef" href="#bib0420">23</a> analysed the diagnostic efficacy of 18F-FDG PET/CT for detecting local treatment failure or intrathoracic recurrences after SBRT treatment in NSCLC patients. Eighty-eight patients were recruited in the study and an 18F-FDG PET/CT control was done 3 months after the ending of SBRT. 18F-FDG PET/CT was positive in 14% (12 of 88 of cases), and was histologically confirmed as true positive in 67% (8 of 12 of cases). On the other hand, 18F-FDG PET/CT resulted negative in 86% of patients (76 of 88 of cases), being confirmed as true negative in 89% 68 of 76) of cases. Therefore, sensitivity, specificity, positive predictive value, and negative predictive value were 50.0, 94.0, 67.0, 89.0, respectively. The authors concluded that an 18F-FDG PET/CT scan performed 3 months after SBRT treatment of a NSCLC was highly specific but with a relatively low sensitivity for the detection of recurrent disease. Yet, they recommend ceCT (every 6 months for the first 2 years and every year thereafter<a class="elsevierStyleCrossRef" href="#bib0310">1</a> instead of 18F-FDG PET/CT in this situation. Moreover, they suggested that 18F-FDG PET/CT should be reserved (a) for those cases with suspected distant metastatic spread, or (b) to evaluate new abnormalities found on ceCT, or (c) during the subsequent follow-up to evaluate the decrease of inflammation related to radiation therapy.Another study by Zhang et al.<a class="elsevierStyleCrossRef" href="#bib0425">24</a> on lung cancer patients treated with SBRT, analysed whether 18F-FDG PET/CT SUV value measured after SBRT could predict local recurrence. They included 128 patients with 140 biopsy-proven NSCLC tumours, in whom 506 18F-FDG PET/CT scans were done. 18F-FDG PET/CT was done between 1 and 6 months after SBRT and subsequently as clinically indicated (median follow-up 31 months). They concluded 18F-FDG PET/CT was helpful for distinguishing SBRT-induced parenchymal consolidation from local recurrence. Moreover, high SUVs (>5.0) obtained more than 6 months after SBRT for NSCLC were associated with local recurrence and should prompt biopsy to confirm malignancy.<a class="elsevierStyleCrossRef" href="#bib0425">24</a>A similar study by Takeda et al.<a class="elsevierStyleCrossRef" href="#bib0430">25</a> including 154 NSCLC patients with 214 18F-FDG PET/CT scans done one year after SBRT for the detection of local recurrence reported a sensitivity and specificity of 100% and 96%–98%, respectively. Whereas this study analyses the performance of 18F-FDG PET/CT studies done one year after SBRT, Van Loon et al.<a class="elsevierStyleCrossRef" href="#bib0435">26</a> reported that early 18F-FDG PET/CT scans 3 months after radical chemo-radiotherapy with curative intent helped to detect progressive disease (PD). They prospectively included 100 patients with NSCLC who had undergone a 18F-FDG PET/CT scan 3 months after initiation of radiotherapy. Progressive disease (PD) was diagnosed in 24 patients, of whom 16 were asymptomatic. In the subgroup of symptomatic patients, the impact on management of 18F-FDG PET/CT was limited because no curative treatment could be offered as an alternative. Instead, in the asymptomatic subgroup, in 3/8 patients with PD another option of radical treatment was offered. As PD in the asymptomatic patients was diagnosed with 18F-FDG PET/CT but not with ceCT, the authors concluded that it is probable that asymptomatic patients are the ones that could take advantage from an early 18F-FDG PET/CT scan.<a class="elsevierStyleCrossRef" href="#bib0435">26</a>A frequent finding after radiotherapy is the presence of a variable and persistent 18F-FDG uptake. Of note, Hoopes et al.<a class="elsevierStyleCrossRef" href="#bib0440">27</a> presented a small population of inoperable stage I NSCLC patients after SBRT treatment, reporting persistent and moderately intense 18F-FDG uptake up to two years after SBRT. This uptake could be related to inflammation and fibrosis, which is probably more persistent after SBRT compared to conventional radiotherapy.Restaging after radiofrequency ablation (RFA) or microwave ablation (MWA)Besides surgery and SBRT, radiofrequency ablation (RFA) is another option for patients with stage I NSCLC. Following RFA the most frequent type of recurrence is loco-regional.<a class="elsevierStyleCrossRef" href="#bib0310">1</a> RFA, similarly to SBRT, also causes GGO in the lung parenchyma around the treated tumour site. Different algorithms including 18F-FDG PET/CT 3–6 months after RFA have been proposed for a close follow-up of these patients.Yoo et al.<a class="elsevierStyleCrossRef" href="#bib0445">28</a> evaluated the performance of early post-ablation 18F-FDG PET/CT in assessing the efficacy of the RFA in stage I NSCLC patients. They included 30 patients with inoperable stage I NSCLC who underwent three 18F-FDG PET/CT scans: (a) baseline, (b) the second within 4 days after RFA, and the third 6 months after RFA. They concluded that very early (4 days) post RFA 18F-FDG PET/CT is not useful while the 6-month post RFA 18F-FDG PET/CT correlated with the clinical outcome at 1 year.Cost-effectivenessSome cost-analysis studies suggest that a 18F-FDG PET/CT performed three months after curative intent (chemo-) radiotherapy is more cost-effective than ceCT, especially in asymptomatic patients.<a class="elsevierStyleCrossRefs" href="#bib0435">26,29</a>PET/CT in restaging of distant metastasesAt initial diagnosis of NSCLC, 18%–36% of patients have distant metastases. The detection of distant spread at initial staging has a pivotal role in order to decide the most appropriate management option; in fact, M staging has a direct impact on management and prognosis. Furthermore, in about 20% of patients who had apparently been radically treated for a NSCLC, will have a disease relapse due to disease understaging at primary diagnosis. Metastases of NSCLC are usually located in the adrenal glands, bones, brain, liver.<a class="elsevierStyleCrossRefs" href="#bib0455">30,31</a>Regarding adrenal lesions, 18F-FDG PET has demonstrated a good performance in differentiating benign from metastatic lesions in patients with cancer. Few studies have specifically addressed this issue in lung cancer patients.<a class="elsevierStyleCrossRefs" href="#bib0460">32,33</a>With regard to bone metastases, 18F-FDG PET has proven higher sensitivity and specificity than bone scintigraphy.<a class="elsevierStyleCrossRefs" href="#bib0470">34-36</a> Instead, the more accurate method for liver lesions is MR, followed by PET/CT and ceCT. MR is also the more accurate method to detect brain metastases, being 18F-FDG PET limited by the high physiologic FDG uptake in the normal brain. Other non-18F-FDG PET/CT tracers must be considered for brain metastases as 11C-timidine.In a meta-analysis that evaluated the performance of 18F-FDG PET/CT for the detection of distant metastases in various solid tumours, forty-one studies and 4,305 patients were included.<a class="elsevierStyleCrossRef" href="#bib0385">37</a> Of these, the studies with data on lung cancer were five, including 578 patients. The pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of 18F-FDG PET/CT were 0.91, 0.96, 25.9, and 0.09, respectively. It was concluded that 18F-FDG PET/CT has an excellent diagnostic performance for the detection of distant metastases in patients with various cancers, especially in lung cancer, breast cancer and head and neck cancer.PET/CT in treatment response evaluationPersonalised medicine is based on tailoring treatments to the individual patient. To this purpose, it is of utmost importance to have tools that provide an early and precise assessment of response to therapy.<a class="elsevierStyleCrossRefs" href="#bib0310">1,30,31</a> Traditionally, tumour response has been assessed comparing the tumour size on ceCT before and after treatment, previously in two dimensions (World Health Organisation, WHO),<a class="elsevierStyleCrossRef" href="#bib0495">38</a> and more recently in one dimension (response evaluation criteria in solid tumours, RECIST).<a class="elsevierStyleCrossRef" href="#bib0500">39</a>18F-FDG PET/CT provides metabolic changes that are typically detected earlier than morphologic changes. In this regard, early assessment of response can be of great value in patients with lung cancer. A large proportion of patients undergo treatments that are toxic and expensive without showing a significant response.<a class="elsevierStyleCrossRef" href="#bib0505">40</a> Early assessment of response to therapy can help tailor treatments in order to continue treatments in patients who are responding to therapy, and discontinue treatments and change to second-line treatments in non-responders. Current evidence in this setting shows that 18F-FDG PET/CT response is probably earlier and more accurate that CT response.<a class="elsevierStyleCrossRefs" href="#bib0310">1,40</a> However, a key issue to be solved is related to the need of standardising the methodology. The European Association of Nuclear Medicine (EANM) has 18F-FDG PET/CT procedure guidelines for tumour imaging updated in 2015, focusing on harmonisation and standarisation of the protocols in order to make the methodology and results comparable worldwide. <a class="elsevierStyleCrossRef" href="#bib0360">11</a> In this regard, one of the methodology aspects that needs to be standardised in the response assessment studies is the timing of the 18F-FDG PET/CT.<a class="elsevierStyleCrossRefs" href="#bib0310">1,11</a> The best timing has not been standardised yet as there is not enough evidence. If done too early it might overestimate FDG uptake because glucose metabolism might be present in cells that are lethally damaged and because of inflammatory processes in responding tissues. If it is done too late other problems might appear, such as late evaluation of response or the risk of tumour repopulation. In summary, large-scale trials are needed, applying strict methodological standardisation.<a class="elsevierStyleCrossRef" href="#bib0310">1</a>PET/CT in patient management decisionsThe introduction of 18F-FDG PET/CT in lung cancer in particular and in oncological patients in general has changed the paradigm in oncological imaging, changing patient management in patients as a consequence of the information provided by PET. The growing evidence is supported not only by original studies but also by systematic reviews and meta-analyses. <a class="elsevierStyleCrossRefs" href="#bib0510">41-46</a> Furthermore, this change in paradigm of oncological imaging can be seen with the introduction of 18F-FDG PET/CT in many clinical guidelines, such as the essential requirements for quality cancer care developed by the European Cancer Organisation (ECCO). <a class="elsevierStyleCrossRefs" href="#bib0540">47-50</a>Conclusions18F-FDG PET/CT can be considered a reliable method in the diagnostic management of lung cancer. Even if it has been demonstrated as a useful tool in differentiating malignant versus benign pulmonary nodules and in the diagnostic work-up, the main utilisation of PET/CT is that of identifying the recurrent disease. Thanks to its ability in differentiating local relapse (showing a high avidity for 18F-FDG) from non-tumoral residual masses (such as post-surgical changes or post-radiation fibrosis), it can be particularly useful in re-staging the tumour for detecting local recurrence (after surgery, radiation therapy and RFA ablation), showing a better accuracy than conventional imaging (ceCT). Moreover, as a highly sensitive, whole-body technique, 18F-FDG PET/CT can provide major information in the detection of distant metastases (“M” staging and re-staging of the disease), with a high impact in the therapeutic management. Finally, 18F-FDG PET/CT seems to be more accurate than ceCT in the assessment of response to therapy, that is of utmost importance in order to continue therapy in responding and change therapy it in non-responding patients.Conflict of interestThe authors declare no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres1214685" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1130583" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1214686" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1130584" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "F-FDG PET/CT in the diagnosis and staging of NSCLC" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "FDG PET/CT in restaging loco-regional recurrence" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "PET/CT in cancer restaging after surgery alone" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "PET/CT after surgery & chemotherapy, chemo-radiotherapy or radiotherapy alone" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "PET/CT after stereotactic body radiation therapy (SBRT)" ] 3 => array:2 [ "identificador" => "sec0035" "titulo" => "Restaging after radiofrequency ablation (RFA) or microwave ablation (MWA)" ] 4 => array:2 [ "identificador" => "sec0040" "titulo" => "Cost-effectiveness" ] ] ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "PET/CT in restaging of distant metastases" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "PET/CT in treatment response evaluation" ] 9 => array:2 [ "identificador" => "sec9045" "titulo" => "PET/CT in patient management decisions" ] 10 => array:2 [ "identificador" => "sec0055" "titulo" => "Conclusions" ] 11 => array:2 [ "identificador" => "sec0060" "titulo" => "Conflict of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-01-21" "fechaAceptado" => "2019-02-06" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1130583" "palabras" => array:6 [ 0 => "Lung cancer" 1 => "FDG PET/CT" 2 => "Staging" 3 => "Restaging" 4 => "Monitoring treatment response" 5 => "Prognostic value" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1130584" "palabras" => array:6 [ 0 => "Cáncer de pulmón" 1 => "FDG PET/TC" 2 => "Estadificación" 3 => "Restadificación" 4 => "Monitorización de la respuesta al tratamiento" 5 => "Valor pronóstico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Lung cancer is a fairly common malignancy. An early diagnosis and a reliable staging and re-staging with the aim to detect both local and distant relapse are of utmost importance in planning the therapeutic management. The imaging diagnostic work-up of patients with lung cancer usually includes conventional imaging (chest X-ray, contrast-enhanced CT , bone scan) and more recently 18F-FDG PET/CT. Great advances in the management of lung cancer are based on the information provided by 18F-FDG PET/CT, as it supplies both metabolic and anatomic information (better localisation). There is vast evidence in the literature demonstrating its utility in (a) characterising benign versus. malignant solitary nodules, (b) staging and re-staging lung cancer, (c) guiding the type of therapy, (d) monitoring treatment response and (e) predicting outcome. In particular, given its specificity in differentiating 18F-FDG-avid relapse from post-surgical changes or post-radiation fibrosis (which do nott take up 18F-FDG), PET/CT can detect recurrent disease after initial treatment and (being a whole-body technique) and has demonstrated high accuracy in the detection of distant metastases or secondary tumours. In conclusion, 18F-FDG PET/CT can be considered a highly accurate and reliable method for staging and re-staging lung cancer, and is highly effective in guiding personalised therapies." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El cáncer de pulmón es una neoplasia maligna bastante común. Un diagnóstico precoz y una estadificación y re-estadificación confiables, con el objetivo de detectar recaídas tanto locales como distantes, son de suma importancia en la planificación del manejo terapéutico. La evaluación diagnóstica de los pacientes con cáncer de pulmón generalmente incluye imágenes convencionales (radiografía de tórax, TC con contraste, gammagrafía ósea) y, más recientemente, PET/TC con 18F-FDG. El gran avance en el manejo del cáncer de pulmón derivado de la PET/TC con 18F-FDG proporciona información tanto metabólica como anatómica (mejor localización): existe una gran evidencia en la literatura que demuestra su utilidad en a) caracterizar nódulos solitarios benignos versus malignos, b) estadificación del cáncer de pulmón y re-estadificación, c) guía del tipo de terapia, d) seguimiento de la respuesta al tratamiento, e) predicción de resultados. En particular, gracias a su especificidad en la diferenciación de la recidiva con avidez por 18F-FDG de los cambios postquirúrgicos o de la fibrosis posradiación (que no captan 18F-FDG), la PET/TC puede detectar una enfermedad recurrente después del tratamiento inicial y (siendo una técnica de cuerpo completo ) y demuestra una alta precisión en la detección de metástasis a distancia o tumores secundarios. En conclusión, la PET/TC con 18F-FDG se puede considerar un método altamente preciso y confiable para estadificar y re-estadificar el cáncer de pulmón, y es muy eficaz para guiar terapias personalizadas." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Delgado Bolton RC, Calapaquí-Terán AK, Giammarile F, Rubello D. The role of 18 F-FDG PET/CT in establishing new clinical and therapeutic modalities in lung cancer. A short review. El papel de F18-FDG-PET/CT en el establecimiento de nuevas modalidades clínicas y terapéuticas en el cáncer de pulmón. Una breve revisión. Rev Esp Med Nucl Imagen Mol. 2019;38:229–233." ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diagnosis and staging \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">I. Differential diagnosis of malignant versus benign pulmonary nodules \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ia. ceCT provides only morphological findings \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IIa. 18F-FDG PET/CT provides both morphological and functional data (this is particularly relevant in differential diagnosis of small lung benign/malignant lesion. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">II. Staging of lung cancer \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ia. ceCT maintains its paramount value in describing the characteristic of the primary T: morphology, inhomogeneity, shape, irregular margins, connections with the surrounding structures, especially the mediastinum and pleura. ceCT major limitation is related to the fact that it relies exclusively on morphological aspects. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IIb. 18F-FDG PET/CT provides information on metabolic function that is strictly related to malignant lesions. Limitations may be related to granulous lesions as sarcoidosis, mycosis, infection. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IIc. Thoracoscopy/broncoscopy are even more reserved to doubtful cases at previous exams. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">III. Restaging in recurrect tumour \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IIIa. CeCT may gives false positive results in post-RT and surgical athelectasis, pharenchima consolidations, and radiation-induced fibrosis. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IIIb. The above ceCT limitations are avoided with PET/CT is performed 2 mo. after rediotherapy and 1 mo. after chemotherapy. Distant metastases are easily detected by PET/CT in contract to ceCT. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Type of treatments \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">I. Surgery alone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">In early stage alone, stage I (18F-FDG PET/CT has demonstrated to be superior to ceCT) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">II. Concomitant surgery & chemotherapy, chemo-radiotherapy or radiotherapy alone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Combined therapies delivered in advanced stage of disease. Radiotherapy alone also for palliation (18F-FDG PET/CT had demonstrated to be superior to ceCT in depicting disease relapse) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">III. Stereotactic Body Radiation Therapy (SBRT) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Only in intrathorax relapse of an early stage tumour (18F-FDG PET/CT had demonstrated to be superior to ceCT in depicting disease relapse) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IV. Restaging after radiofrequency ablation (RFA) or microwave ablation (MWA) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Only in intrathorax relapse of an early stage tumour 18F-FDG PET/CT has demonstrated to be superior to ceCT in depicting disease relapse in some studies and vice versa in others) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V. PET/CT in treatment response evaluation and prognosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Many studies have proven the superiority of PET/CT in comparison to ceCT in treatment response evaluation and prognosis \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2073713.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Diagnosis, staging and therapies in lung cancer." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:50 [ 0 => array:3 [ "identificador" => "bib0310" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Appropriate use criteria for FDG PET/CT restaging and treatment response assessment of malignant disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. 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Role of 18F-FDG-PET/CT in establishing new clinical and therapeutic modalities in lung cancer. A short review

El papel de la PET/CT con 18F-FDG en el establecimiento de nuevas modalidades clínicas y terapéuticas en el cáncer de pulmón. Una breve revisión

Roberto C. Delgado Boltona, Adriana K. Calapaquí-Teránb, Francesco Giammarilec, Domenico Rubellod,

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domenico.rubello@libero.it

Corresponding author.

a Department of Diagnostic Imaging (Radiology) and Nuclear Medicine at the San Pedro University Hospital and Centre for Biomedical Research of La Rioja (CIBIR) in Logroño (La Rioja), Spain

b Department of Pathology at the University Hospital Marqués de Valdecilla, Santander (Cantabria), Spain

c Nuclear Medicine and Diagnostic Imaging Section, International Atomic Energy Agency (IAEA), Vienna, Austria

d Department of Imaging (Nuclear Medicine, Medical Physics, Radiology) and of Clinical Laboratory (Laboratory, Transfusional Centre, Microbiology, Pathology, Rovigo Hospital, Italy

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        "afiliaciones" => array:4 [
          0 => array:3 [
            "entidad" => "Department of Diagnostic Imaging &#40;Radiology&#41; and Nuclear Medicine at the San Pedro University Hospital and Centre for Biomedical Research of La Rioja &#40;CIBIR&#41; in Logro&#241;o &#40;La Rioja&#41;&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
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          1 => array:3 [
            "entidad" => "Department of Pathology at the University Hospital Marqu&#233;s de Valdecilla&#44; Santander &#40;Cantabria&#41;&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "aff9010"
          ]
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            "entidad" => "Nuclear Medicine and Diagnostic Imaging Section&#44; International Atomic Energy Agency &#40;IAEA&#41;&#44; Vienna&#44; Austria"
            "etiqueta" => "c"
            "identificador" => "aff0010"
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          3 => array:3 [
            "entidad" => "Department of Imaging &#40;Nuclear Medicine&#44; Medical Physics&#44; Radiology&#41; and of Clinical Laboratory &#40;Laboratory&#44; Transfusional Centre&#44; Microbiology&#44; Pathology&#44; Rovigo Hospital&#44; Italy"
            "etiqueta" => "d"
            "identificador" => "aff0015"
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            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
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    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "El papel de la PET&#47;CT con <span class="elsevierStyleSup">18</span>F-FDG en el establecimiento de nuevas modalidades cl&#237;nicas y terap&#233;uticas en el c&#225;ncer de pulm&#243;n&#46; Una breve revisi&#243;n"
      ]
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Non-small cell lung cancer &#40;NSCLC&#41; represents 85&#37;&#8211;90&#37; of all lung cancers&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">1</span></a> It includes three main sub-types&#58; &#40;a&#41; squamous-cell carcinoma&#44; &#40;b&#41; adenocarcinoma&#44; and &#40;c&#41; large-cell carcinoma&#46; The first two sub-types account for about 80&#37; of all lung cancers worldwide&#46; NSCLC is predominantly associated with smoking and usually present as large tumours in the centre of the lung&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">2&#44;3</span></a> In contrast&#44; adenocarcinomas are frequently located in the peripheral areas of the lungs&#44; and are divided into the following subtypes&#58; &#40;a&#41; acinar&#44; &#40;b&#41; papillary&#44; &#40;c&#41; bronchiolo-alveolar carcinoma &#40;BAC&#41;&#44; and &#40;d&#41; solid adenocarcinoma with relevant mucin production&#46; In non-smokers&#44; the most frequent type of lung cancer is the adenocarcinoma&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">4</span></a> Mixed histologic patterns are present in many cases&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030"><span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in the diagnosis and staging of NSCLC</span><p id="par0010" class="elsevierStylePara elsevierViewall">The imaging diagnostic work-up of patients with lung NSCLC includes chest X-ray&#44; contrast-enhanced CT &#40;ceCT&#41;&#44; bone scintigraphy&#44; and more recently <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT and&#44; in bronchial neuroendocrine tumours &#40;NET&#41; <span class="elsevierStyleSup">111</span>In planar and SPECT somatostatin receptor scintigraphy &#40;SRS&#41;&#44; which has been recently substituted by PET&#47;CT with <span class="elsevierStyleSup">68</span>Ga-DOTA-peptides mainly DOTA-TOC&#44; DOTA-NOC&#44; DOTA-TATE&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In this context&#44; ceCT has been the gold standard imaging technique for many decades&#44; and still maintains a pivotal role in evaluating the primary tumour features &#40;morphology&#44; inhomogeneity&#44; shape&#44; irregular margins and so forth&#41; as well as the connections with the surrounding structures&#44; especially the mediastinum and pleura&#46; ceCT major limitation is related to the fact that it relies exclusively on morphological aspects&#44; while <span class="elsevierStyleSup">18</span>F-FDG and <span class="elsevierStyleSup">68</span>Ga-DOTA-peptides using hybrid PET&#47;CT scanners are able to provide both metabolic and accurate anatomic information in a single exam&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">1&#44;6</span></a>As reported before&#44; <span class="elsevierStyleSup">18</span>F-FDG is the most commonly used PET tracer&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT has been extensively studied in lung cancer&#46; There is large evidence in literature showing its utility in&#58; &#40;a&#41; characterising benign versus malignant solitary pulmonary nodules&#44;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">1&#44;4</span></a> &#40;b&#41; in the staging and re-staging of lung cancer&#44;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">1&#44;4&#44;6&#44;7</span></a> &#40;c&#41; guiding surgical&#44; chemo- and&#47;or radiotherapy treatments&#44;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">7&#44;8</span></a> &#40;d&#41; monitoring treatment response<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">1&#44;7-9</span></a> and &#40;e&#41; predicting outcome of lung cancer&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">1&#44;8&#44;9</span></a> Some of these indications are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Furthermore&#44; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT has demonstrated its utility from a cost-effectiveness point of view compared to thoracoscopy and surgery when systematically performed in all patients with a lung nodule of uncertain origin&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">10</span></a> As a consequence of the building evidence in favour of PET&#47;CT in lung cancer&#44; it has been progressively included in guidelines and consensus documents&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">1&#44;5&#44;11&#44;12</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">FDG PET&#47;CT in restaging loco-regional recurrence</span><p id="par0025" class="elsevierStylePara elsevierViewall">As a whole&#44; mainly depending from the hystologic subtipes and TNM&#44; lung cancer relapses after primary treatment in 30&#37;&#8211;75&#37; of patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">2&#44;3</span></a> As in other cancers&#44; after initial treatment &#40;surgery&#44; chemio-radiotherapy&#41;&#44; differentiating local-regional recurrence from post-surgical non-tumoral changes as athelectasis&#44; pharenchima consolidations&#44; and radiation-induced fibrosis&#44; may be difficult when using ceCT alone&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">1&#44;4</span></a> In this regard&#44; a great help derives from <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT which has the great advantage of evidencing areas with high <span class="elsevierStyleSup">18</span>F-FDG uptake by metabolically active tissues&#44; suggestive of cancer remnant&#47;recurrence&#44; thus providing relevant information for planning subsequent therapies&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">1&#44;4&#44;11-14</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">It should be kept in mind that recent radiotherapy may provide false positive results related to inflammation&#46; To solve this problem&#44; a PET&#47;CT control is performed two or three months after the end of radiotherapy&#44; when <span class="elsevierStyleSup">18</span>F-FDG-inflammatory uptake typically decreases to very low or absent values&#44; therefore excluding persistent&#47;recurrent tumour&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">1&#44;8&#44;10</span></a> However&#44; the positive results due to active inflammation&#44; are now being used in the diagnosis of infection and inflammation demonstrating a good diagnostic performance&#44; such as cases of infective endocarditis or vasculitis&#46;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">15-18</span></a> On the other hand a PET&#47;CT control performed close to chemotherapy may give a false negative result&#58; so it is recommended in clinical practice to allow for a time interval longer than 1 month to perform a PET&#47;CT after the end of chemotherapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">1&#44;3&#44;4&#44;8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Recurrence of NSCLC may be classified as loco-regional relapse or distant metastatic spread&#44; the latter being the most common form of NSCLC recurrence&#46; Depending on the initial stage at diagnosis and on the treatment applied&#44; metastatic recurrence comprehends 39&#37;&#8211;65&#46;5&#37; of cases&#44; whereas the remaining 30&#37; are limited and defined as loco-regional recurrence&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">1&#44;2&#44; 4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Yet&#44; loco-regional recurrence is typically located within the treated hemithorax&#44; usually presenting as nodules that involve the surgically treated area or the area treated by radiofrequency or microwave ablation&#44; and in other ipsilateral thoracic structures &#40;bronchial stump&#44; pleura&#44; chest wall&#44; and lymph nodes&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">1&#44;4&#44;19</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Lastly&#44; apart from recurrences&#44; new primary lung cancer is reported in 1&#37;&#8211;2&#37; of NSCLC patients per year after initial radical therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">20</span></a></p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">PET&#47;CT in cancer restaging after surgery alone</span><p id="par0050" class="elsevierStylePara elsevierViewall">The study by Toba et al&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">21</span></a> retrospectively included 101 NSCLC patients who had undergone potentially curable operations and were followed by an <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT controls every subsequent year &#40;for a total of 233 <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT studies&#41;&#44; in order to select patients without clinical or radiological evidence of recurrence&#46; Of relevance&#44; eighteen &#40;18&#37;&#41; asymptomatic patients had recurrent disease and 22 recurrent sites were confirmed&#58; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT correctly diagnosed recurrence in 17 of the 18 &#40;94&#37;&#41; patients and 21 of the 22 &#40;95&#37;&#41; recurrent sites&#46; Sensitivity&#44; specificity&#44; positive predictive value&#44; negative predictive value&#44; and accuracy were 94&#46;4&#44; 97&#46;6&#44; 89&#46;5&#44; 98&#46;8 and 97&#46;0&#44; respectively&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Another study by Choi et al&#46; analysed the performance of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT for detecting recurrent disease after initial intent curative surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">22</span></a> They included a large series of 358 patients who had undergone complete resection of NSCLC and that then were followed-up with <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT and other conventional imaging methods &#40;ceCT&#44; bone scan&#41;&#46; Recurrent disease occurred in 31&#37; of patients&#58; recurrence disease was detected both with ceCT and <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in 51&#37; of patients and only by <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in 37&#37; of cases&#46; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT was false negative in 6 small or hypometabolic recurrent lesions&#46; Because of this&#44; the authors recommended an annual screening method including both <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT and a chest ceCT&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">PET&#47;CT after surgery &#38; chemotherapy&#44; chemo-radiotherapy or radiotherapy alone</span><p id="par0060" class="elsevierStylePara elsevierViewall">A meta-analysis evaluated the diagnostic efficacy of PET and PET&#47;CT with <span class="elsevierStyleSup">18</span>F-FDG compared to conventional imaging &#40;CI&#41; techniques &#40;ceCT&#44; bone scan&#41; for the detection of recurrent lung cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">19</span></a> Thirteen articles and 1&#44;035 patients were included&#46; Pooled sensitivity for PET&#44; PET&#47;CT&#44; and CI were 0&#46;94&#44; 0&#46;90&#44; and 0&#46;78&#44; respectively&#46; Pooled specificity for PET&#44; PET&#47;CT&#44; and CI were 0&#46;84&#44; 0&#46;90&#44; and 0&#46;80&#44; respectively&#46; With regards to sensitivity&#44; lower values were associated with CI than PET &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&#41; and PET&#47;CT &#40;<span class="elsevierStyleItalic">p<span class="elsevierStyleHsp" style=""></span></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#41;&#44; and there was no significant difference between PET&#47;CT and PET &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;1&#41;&#46; Regarding specificity&#44; values for PET&#47;CT and PET were significantly higher than CI &#40;both <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000&#41;&#44; with no significant difference between PET&#47;CT and PET &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;2&#41;&#46; The analysis with SROC curves evidenced a better diagnostic accuracy associated with PET&#47;CT than PET and CI&#46; They concluded that PET&#47;CT and PET were superior imaging modalities for the detection of recurrent lung cancer&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Other studies not included in the above mentioned systematic review and meta-analysis also found that PET&#47;CT was associated with high specificity for the detection of recurrent disease following initial treatments&#44; including homogeneous patient populations treated with surgery&#44; radiotherapy&#44; or radiofrequency ablation&#46; These therapeutic modalities are discussed below in the text&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">PET&#47;CT after stereotactic body radiation therapy &#40;SBRT&#41;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Stereotactic body radiation therapy &#40;SBRT&#41; is an established treatment option for early-stage lung cancer&#46; SBRT causes focal changes in the lung parenchyma close to the tumour site&#44; most frequently represented by a ground glass opacity &#40;GGO&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">1</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">The study by Pastis et al&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">23</span></a> analysed the diagnostic efficacy of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT for detecting local treatment failure or intrathoracic recurrences after SBRT treatment in NSCLC patients&#46; Eighty-eight patients were recruited in the study and an <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT control was done 3 months after the ending of SBRT&#46; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT was positive in 14&#37; &#40;12 of 88 of cases&#41;&#44; and was histologically confirmed as true positive in 67&#37; &#40;8 of 12 of cases&#41;&#46; On the other hand&#44; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT resulted negative in 86&#37; of patients &#40;76 of 88 of cases&#41;&#44; being confirmed as true negative in 89&#37; 68 of 76&#41; of cases&#46; Therefore&#44; sensitivity&#44; specificity&#44; positive predictive value&#44; and negative predictive value were 50&#46;0&#44; 94&#46;0&#44; 67&#46;0&#44; 89&#46;0&#44; respectively&#46; The authors concluded that an <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT scan performed 3 months after SBRT treatment of a NSCLC was highly specific but with a relatively low sensitivity for the detection of recurrent disease&#46; Yet&#44; they recommend ceCT &#40;every 6 months for the first 2 years and every year thereafter<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">1</span></a> instead of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in this situation&#46; Moreover&#44; they suggested that <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT should be reserved &#40;a&#41; for those cases with suspected distant metastatic spread&#44; or &#40;b&#41; to evaluate new abnormalities found on ceCT&#44; or &#40;c&#41; during the subsequent follow-up to evaluate the decrease of inflammation related to radiation therapy&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Another study by Zhang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">24</span></a> on lung cancer patients treated with SBRT&#44; analysed whether <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT SUV value measured after SBRT could predict local recurrence&#46; They included 128 patients with 140 biopsy-proven NSCLC tumours&#44; in whom 506 <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT scans were done&#46; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT was done between 1 and 6 months after SBRT and subsequently as clinically indicated &#40;median follow-up 31 months&#41;&#46; They concluded <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT was helpful for distinguishing SBRT-induced parenchymal consolidation from local recurrence&#46; Moreover&#44; high SUVs &#40;&#62;5&#46;0&#41; obtained more than 6 months after SBRT for NSCLC were associated with local recurrence and should prompt biopsy to confirm malignancy&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">24</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">A similar study by Takeda et al&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">25</span></a> including 154 NSCLC patients with 214 <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT scans done one year after SBRT for the detection of local recurrence reported a sensitivity and specificity of 100&#37; and 96&#37;&#8211;98&#37;&#44; respectively&#46; Whereas this study analyses the performance of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT studies done one year after SBRT&#44; Van Loon et al&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">26</span></a> reported that early <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT scans 3 months after radical chemo-radiotherapy with curative intent helped to detect progressive disease &#40;PD&#41;&#46; They prospectively included 100 patients with NSCLC who had undergone a <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT scan 3 months after initiation of radiotherapy&#46; Progressive disease &#40;PD&#41; was diagnosed in 24 patients&#44; of whom 16 were asymptomatic&#46; In the subgroup of symptomatic patients&#44; the impact on management of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT was limited because no curative treatment could be offered as an alternative&#46; Instead&#44; in the asymptomatic subgroup&#44; in 3&#47;8 patients with PD another option of radical treatment was offered&#46; As PD in the asymptomatic patients was diagnosed with <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT but not with ceCT&#44; the authors concluded that it is probable that asymptomatic patients are the ones that could take advantage from an early <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT scan&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">26</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">A frequent finding after radiotherapy is the presence of a variable and persistent <span class="elsevierStyleSup">18</span>F-FDG uptake&#46; Of note&#44; Hoopes et al&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">27</span></a> presented a small population of inoperable stage I NSCLC patients after SBRT treatment&#44; reporting persistent and moderately intense <span class="elsevierStyleSup">18</span>F-FDG uptake up to two years after SBRT&#46; This uptake could be related to inflammation and fibrosis&#44; which is probably more persistent after SBRT compared to conventional radiotherapy&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Restaging after radiofrequency ablation &#40;RFA&#41; or microwave ablation &#40;MWA&#41;</span><p id="par0100" class="elsevierStylePara elsevierViewall">Besides surgery and SBRT&#44; radiofrequency ablation &#40;RFA&#41; is another option for patients with stage I NSCLC&#46; Following RFA the most frequent type of recurrence is loco-regional&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">1</span></a> RFA&#44; similarly to SBRT&#44; also causes GGO in the lung parenchyma around the treated tumour site&#46; Different algorithms including <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT 3&#8211;6 months after RFA have been proposed for a close follow-up of these patients&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Yoo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">28</span></a> evaluated the performance of early post-ablation <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in assessing the efficacy of the RFA in stage I NSCLC patients&#46; They included 30 patients with inoperable stage I NSCLC who underwent three <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT scans&#58; &#40;a&#41; baseline&#44; &#40;b&#41; the second within 4 days after RFA&#44; and the third 6 months after RFA&#46; They concluded that very early &#40;4 days&#41; post RFA <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT is not useful while the 6-month post RFA <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT correlated with the clinical outcome at 1 year&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Cost-effectiveness</span><p id="par0115" class="elsevierStylePara elsevierViewall">Some cost-analysis studies suggest that a <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT performed three months after curative intent &#40;chemo-&#41; radiotherapy is more cost-effective than ceCT&#44; especially in asymptomatic patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">26&#44;29</span></a></p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">PET&#47;CT in restaging of distant metastases</span><p id="par0120" class="elsevierStylePara elsevierViewall">At initial diagnosis of NSCLC&#44; 18&#37;&#8211;36&#37; of patients have distant metastases&#46; The detection of distant spread at initial staging has a pivotal role in order to decide the most appropriate management option&#59; in fact&#44; M staging has a direct impact on management and prognosis&#46; Furthermore&#44; in about 20&#37; of patients who had apparently been radically treated for a NSCLC&#44; will have a disease relapse due to disease understaging at primary diagnosis&#46; Metastases of NSCLC are usually located in the adrenal glands&#44; bones&#44; brain&#44; liver&#46;<a class="elsevierStyleCrossRefs" href="#bib0455"><span class="elsevierStyleSup">30&#44;31</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Regarding adrenal lesions&#44; <span class="elsevierStyleSup">18</span>F-FDG PET has demonstrated a good performance in differentiating benign from metastatic lesions in patients with cancer&#46; Few studies have specifically addressed this issue in lung cancer patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">32&#44;33</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">With regard to bone metastases&#44; <span class="elsevierStyleSup">18</span>F-FDG PET has proven higher sensitivity and specificity than bone scintigraphy&#46;<a class="elsevierStyleCrossRefs" href="#bib0470"><span class="elsevierStyleSup">34-36</span></a> Instead&#44; the more accurate method for liver lesions is MR&#44; followed by PET&#47;CT and ceCT&#46; MR is also the more accurate method to detect brain metastases&#44; being <span class="elsevierStyleSup">18</span>F-FDG PET limited by the high physiologic FDG uptake in the normal brain&#46; Other non-<span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT tracers must be considered for brain metastases as <span class="elsevierStyleSup">11</span>C-timidine&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">In a meta-analysis that evaluated the performance of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT for the detection of distant metastases in various solid tumours&#44; forty-one studies and 4&#44;305 patients were included&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">37</span></a> Of these&#44; the studies with data on lung cancer were five&#44; including 578 patients&#46; The pooled sensitivity&#44; specificity&#44; positive likelihood ratio and negative likelihood ratio of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT were 0&#46;91&#44; 0&#46;96&#44; 25&#46;9&#44; and 0&#46;09&#44; respectively&#46; It was concluded that <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT has an excellent diagnostic performance for the detection of distant metastases in patients with various cancers&#44; especially in lung cancer&#44; breast cancer and head and neck cancer&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">PET&#47;CT in treatment response evaluation</span><p id="par0140" class="elsevierStylePara elsevierViewall">Personalised medicine is based on tailoring treatments to the individual patient&#46; To this purpose&#44; it is of utmost importance to have tools that provide an early and precise assessment of response to therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">1&#44;30&#44;31</span></a> Traditionally&#44; tumour response has been assessed comparing the tumour size on ceCT before and after treatment&#44; previously in two dimensions &#40;World Health Organisation&#44; WHO&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">38</span></a> and more recently in one dimension &#40;response evaluation criteria in solid tumours&#44; RECIST&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">39</span></a><span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT provides metabolic changes that are typically detected earlier than morphologic changes&#46; In this regard&#44; early assessment of response can be of great value in patients with lung cancer&#46; A large proportion of patients undergo treatments that are toxic and expensive without showing a significant response&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">40</span></a> Early assessment of response to therapy can help tailor treatments in order to continue treatments in patients who are responding to therapy&#44; and discontinue treatments and change to second-line treatments in non-responders&#46; Current evidence in this setting shows that <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT response is probably earlier and more accurate that CT response&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">1&#44;40</span></a> However&#44; a key issue to be solved is related to the need of standardising the methodology&#46; The European Association of Nuclear Medicine &#40;EANM&#41; has <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT procedure guidelines for tumour imaging updated in 2015&#44; focusing on harmonisation and standarisation of the protocols in order to make the methodology and results comparable worldwide&#46; <a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">11</span></a> In this regard&#44; one of the methodology aspects that needs to be standardised in the response assessment studies is the timing of the <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">1&#44;11</span></a> The best timing has not been standardised yet as there is not enough evidence&#46; If done too early it might overestimate FDG uptake because glucose metabolism might be present in cells that are lethally damaged and because of inflammatory processes in responding tissues&#46; If it is done too late other problems might appear&#44; such as late evaluation of response or the risk of tumour repopulation&#46; In summary&#44; large-scale trials are needed&#44; applying strict methodological standardisation&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec9045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect9065">PET&#47;CT in patient management decisions</span><p id="par1120" class="elsevierStylePara elsevierViewall">The introduction of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in lung cancer in particular and in oncological patients in general has changed the paradigm in oncological imaging&#44; changing patient management in patients as a consequence of the information provided by PET&#46; The growing evidence is supported not only by original studies but also by systematic reviews and meta-analyses&#46; <a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">41-46</span></a> Furthermore&#44; this change in paradigm of oncological imaging can be seen with the introduction of <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT in many clinical guidelines&#44; such as the essential requirements for quality cancer care developed by the European Cancer Organisation &#40;ECCO&#41;&#46; <a class="elsevierStyleCrossRefs" href="#bib0540"><span class="elsevierStyleSup">47-50</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conclusions</span><p id="par0145" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT can be considered a reliable method in the diagnostic management of lung cancer&#46; Even if it has been demonstrated as a useful tool in differentiating malignant versus benign pulmonary nodules and in the diagnostic work-up&#44; the main utilisation of PET&#47;CT is that of identifying the recurrent disease&#46; Thanks to its ability in differentiating local relapse &#40;showing a high avidity for <span class="elsevierStyleSup">18</span>F-FDG&#41; from non-tumoral residual masses &#40;such as post-surgical changes or post-radiation fibrosis&#41;&#44; it can be particularly useful in re-staging the tumour for detecting local recurrence &#40;after surgery&#44; radiation therapy and RFA ablation&#41;&#44; showing a better accuracy than conventional imaging &#40;ceCT&#41;&#46; Moreover&#44; as a highly sensitive&#44; whole-body technique&#44; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT can provide major information in the detection of distant metastases &#40;&#8220;M&#8221; staging and re-staging of the disease&#41;&#44; with a high impact in the therapeutic management&#46; Finally&#44; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT seems to be more accurate than ceCT in the assessment of response to therapy&#44; that is of utmost importance in order to continue therapy in responding and change therapy it in non-responding patients&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflict of interest</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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          "titulo" => "F-FDG PET&#47;CT in the diagnosis and staging of NSCLC"
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          "titulo" => "FDG PET&#47;CT in restaging loco-regional recurrence"
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              "titulo" => "PET&#47;CT in cancer restaging after surgery alone"
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              "titulo" => "PET&#47;CT after surgery &#38; chemotherapy&#44; chemo-radiotherapy or radiotherapy alone"
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              "identificador" => "sec0030"
              "titulo" => "PET&#47;CT after stereotactic body radiation therapy &#40;SBRT&#41;"
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              "identificador" => "sec0035"
              "titulo" => "Restaging after radiofrequency ablation &#40;RFA&#41; or microwave ablation &#40;MWA&#41;"
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              "titulo" => "Cost-effectiveness"
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          "titulo" => "PET&#47;CT in restaging of distant metastases"
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          "titulo" => "PET&#47;CT in treatment response evaluation"
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          "titulo" => "PET&#47;CT in patient management decisions"
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            0 => "Lung cancer"
            1 => "FDG PET&#47;CT"
            2 => "Staging"
            3 => "Restaging"
            4 => "Monitoring treatment response"
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            0 => "C&#225;ncer de pulm&#243;n"
            1 => "FDG PET&#47;TC"
            2 => "Estadificaci&#243;n"
            3 => "Restadificaci&#243;n"
            4 => "Monitorizaci&#243;n de la respuesta al tratamiento"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Lung cancer is a fairly common malignancy&#46; An early diagnosis and a reliable staging and re-staging with the aim to detect both local and distant relapse are of utmost importance in planning the therapeutic management&#46; The imaging diagnostic work-up of patients with lung cancer usually includes conventional imaging &#40;chest X-ray&#44; contrast-enhanced CT &#44; bone scan&#41; and more recently <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT&#46; Great advances in the management of lung cancer are based on the information provided by <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT&#44; as it supplies both metabolic and anatomic information &#40;better localisation&#41;&#46; There is vast evidence in the literature demonstrating its utility in &#40;a&#41; characterising benign versus&#46; malignant solitary nodules&#44; &#40;b&#41; staging and re-staging lung cancer&#44; &#40;c&#41; guiding the type of therapy&#44; &#40;d&#41; monitoring treatment response and &#40;e&#41; predicting outcome&#46; In particular&#44; given its specificity in differentiating <span class="elsevierStyleSup">18</span>F-FDG-avid relapse from post-surgical changes or post-radiation fibrosis &#40;which do nott take up <span class="elsevierStyleSup">18</span>F-FDG&#41;&#44; PET&#47;CT can detect recurrent disease after initial treatment and &#40;being a whole-body technique&#41; and has demonstrated high accuracy in the detection of distant metastases or secondary tumours&#46; In conclusion&#44; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT can be considered a highly accurate and reliable method for staging and re-staging lung cancer&#44; and is highly effective in guiding personalised therapies&#46;</p></span>"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El c&#225;ncer de pulm&#243;n es una neoplasia maligna bastante com&#250;n&#46; Un diagn&#243;stico precoz y una estadificaci&#243;n y re-estadificaci&#243;n confiables&#44; con el objetivo de detectar reca&#237;das tanto locales como distantes&#44; son de suma importancia en la planificaci&#243;n del manejo terap&#233;utico&#46; La evaluaci&#243;n diagn&#243;stica de los pacientes con c&#225;ncer de pulm&#243;n generalmente incluye im&#225;genes convencionales &#40;radiograf&#237;a de t&#243;rax&#44; TC con contraste&#44; gammagraf&#237;a &#243;sea&#41; y&#44; m&#225;s recientemente&#44; PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG&#46; El gran avance en el manejo del c&#225;ncer de pulm&#243;n derivado de la PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG proporciona informaci&#243;n tanto metab&#243;lica como anat&#243;mica &#40;mejor localizaci&#243;n&#41;&#58; existe una gran evidencia en la literatura que demuestra su utilidad en a&#41; caracterizar n&#243;dulos solitarios benignos versus malignos&#44; b&#41; estadificaci&#243;n del c&#225;ncer de pulm&#243;n y re-estadificaci&#243;n&#44; c&#41; gu&#237;a del tipo de terapia&#44; d&#41; seguimiento de la respuesta al tratamiento&#44; e&#41; predicci&#243;n de resultados&#46; En particular&#44; gracias a su especificidad en la diferenciaci&#243;n de la recidiva con avidez por <span class="elsevierStyleSup">18</span>F-FDG de los cambios postquir&#250;rgicos o de la fibrosis posradiaci&#243;n &#40;que no captan <span class="elsevierStyleSup">18</span>F-FDG&#41;&#44; la PET&#47;TC puede detectar una enfermedad recurrente despu&#233;s del tratamiento inicial y &#40;siendo una t&#233;cnica de cuerpo completo &#41; y demuestra una alta precisi&#243;n en la detecci&#243;n de met&#225;stasis a distancia o tumores secundarios&#46; En conclusi&#243;n&#44; la PET&#47;TC con <span class="elsevierStyleSup">18</span>F-FDG se puede considerar un m&#233;todo altamente preciso y confiable para estadificar y re-estadificar el c&#225;ncer de pulm&#243;n&#44; y es muy eficaz para guiar terapias personalizadas&#46;</p></span>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Delgado Bolton RC&#44; Calapaqu&#237;-Ter&#225;n AK&#44; Giammarile F&#44; Rubello D&#46; The role of <span class="elsevierStyleSup">18</span> F-FDG PET&#47;CT in establishing new clinical and therapeutic modalities in lung cancer&#46; A short review&#46; El papel de F18-FDG-PET&#47;CT en el establecimiento de nuevas modalidades cl&#237;nicas y terap&#233;uticas en el c&#225;ncer de pulm&#243;n&#46; Una breve revisi&#243;n&#46; Rev Esp Med Nucl Imagen Mol&#46; 2019&#59;38&#58;229&#8211;233&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Diagnosis and staging</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">I&#46; Differential diagnosis of malignant versus benign pulmonary nodules</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Ia&#46; ceCT provides only morphological findings&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>IIa&#46; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT provides both morphological and functional data &#40;this is particularly relevant in differential diagnosis of small lung benign&#47;malignant lesion&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">II&#46; Staging of lung cancer</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Ia&#46; ceCT maintains its paramount value in describing the characteristic of the primary T&#58; morphology&#44; inhomogeneity&#44; shape&#44; irregular margins&#44; connections with the surrounding structures&#44; especially the mediastinum and pleura&#46; ceCT major limitation is related to the fact that it relies exclusively on morphological aspects&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>IIb&#46; <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT provides information on metabolic function that is strictly related to malignant lesions&#46; Limitations may be related to granulous lesions as sarcoidosis&#44; mycosis&#44; infection&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>IIc&#46; Thoracoscopy&#47;broncoscopy are even more reserved to doubtful cases at previous exams&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">III&#46; Restaging in recurrect tumour</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>IIIa&#46; CeCT may gives false positive results in post-RT and surgical athelectasis&#44; pharenchima consolidations&#44; and radiation-induced fibrosis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>IIIb&#46; The above ceCT limitations are avoided with PET&#47;CT is performed 2 mo&#46; after rediotherapy and 1 mo&#46; after chemotherapy&#46; Distant metastases are easily detected by PET&#47;CT in contract to ceCT&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Type of treatments</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">I&#46; Surgery alone</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>In early stage alone&#44; stage I &#40;<span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT has demonstrated to be superior to ceCT&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">II&#46; Concomitant surgery &#38; chemotherapy&#44; chemo-radiotherapy or radiotherapy alone</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Combined therapies delivered in advanced stage of disease&#46; Radiotherapy alone also for palliation &#40;<span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT had demonstrated to be superior to ceCT in depicting disease relapse&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">III&#46; Stereotactic Body Radiation Therapy &#40;SBRT&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Only in intrathorax relapse of an early stage tumour &#40;<span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT had demonstrated to be superior to ceCT in depicting disease relapse&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">IV&#46; Restaging after radiofrequency ablation &#40;RFA&#41; or microwave ablation &#40;MWA&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Only in intrathorax relapse of an early stage tumour <span class="elsevierStyleSup">18</span>F-FDG PET&#47;CT has demonstrated to be superior to ceCT in depicting disease relapse in some studies and vice versa in others&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">V&#46; PET&#47;CT in treatment response evaluation and prognosis</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Many studies have proven the superiority of PET&#47;CT in comparison to ceCT in treatment response evaluation and prognosis&nbsp;\t\t\t\t\t\t\n
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