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      Role of 18F-FDG PET-CT in head and neck squamous cell carcinoma

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          SUMMARY

          The role of PET-CT imaging in head and neck squamous cell carcinoma during pre-treatment staging, radiotherapy planning, treatment response assessment and post-therapy follow-up is reviewed with focus on current evidence, controversial issues and future clinical applications. In staging, the role of 18F-FDG PET-CT is well recognized for detecting cervical nodal involvement as well as for exclusion of distant metastases and synchronous primary tumours. In the evaluation of treatment response, the high negative predictive value of 18F-FDG PET-CT performed at least 8 weeks from the end of radio-chemotherapy allows prevention of unnecessary diagnostic invasive procedures and neck dissection in many patients, with a significant impact on clinical outcome. On the other hand, in this setting, the low positive predictive value due to possible post-radiation inflammation findings requires special care before making a clinical decision. Controversial data are currently available on the role of PET imaging during the course of radio-chemotherapy. The prognostic role of 18F-FDG PET-CT imaging in head and neck squamous cell carcinoma is recently emerging, in addition to the utility of this technique in evaluation of the tumour volume for planning radiation therapy. Additionally, new PET radiopharmaceuticals could provide considerable information on specific tumour characteristics, thus overcoming the limitations of 18F-FDG.

          RIASSUNTO

          In questa review è analizzato il ruolo della PET-CT nei carcinomi squamosi del distretto testa-collo in fase di stadiazione, nella pianificazione del trattamento radiante, nella valutazione della risposta al trattamento radio-chemioterapico e nel follow-up, tenendo conto dei dati attualmente disponibili, delle questioni controverse e delle future applicazioni cliniche. In fase di stadiazione, è ampiamente riconosciuto il ruolo della PET-CT con 18F-FDG nella valutazione del coinvolgimento linfonodale, nonché nella esclusione della presenza di metastasi a distanza e di tumori primitivi sincroni. Nella valutazione della risposta al trattamento, l'elevato valore predittivo negativo della 18F-FDG PET-CT, effettuata almeno 8 settimane dopo la fine del trattamento radio-chemioterapico, consente di evitare in molti pazienti inutili procedure diagnostiche invasive nonché la dissezione del collo, con conseguente significativo impatto clinico. D'altra parte, in questa fase il basso valore predittivo positivo della metodica, causato dai possibili falsi positivi secondari alla concomitante flogosi post-attinica, deve essere tenuto in particolare considerazione prima di prendere una decisione clinica. Dati controversi sono attualmente disponibili sul ruolo dell'imaging PET durante il trattamento radio-chemioterapico. Negli ultimi anni, è emerso il ruolo prognostico della 18F-FDG PET-CT nei carcinomi a cellule squamose del distretto testa-collo, così come l'utilità di questa tecnica nella valutazione del volume del tumore per la pianificazione del trattamento radiante. Inoltre, nuove prospettive provengono dall'impiego dei nuovi radiofarmaci PET che potrebbero fornire notevoli informazioni su caratteristiche biologiche specifiche del tumore, superando di conseguenza i noti limiti del 18F-FDG.

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          Most cited references72

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          Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography.

          While 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is a useful tumor imaging agent, its intratumoral distribution has not been described well at the cellular level. In order to demonstrate cellular localization of [18F]FDG and 2-deoxy-D-[3H]glucose (3H-DG) uptake by the tumor in vivo, C3H/He mice transplanted subcutaneously with FM3A tumors were studied 1 hr after intravenous injection of [18F]FDG or 3H-DG using micro- and macro-autoradiography. Fluorine-18-FDG and 3H-DG showed the same distribution pattern in the tumor with both autoradiographic methods. The newly formed granulation tissue around the tumor and macrophages, which were massively infiltrating the marginal areas surrounding necrotic area of the tumor showed a higher uptake of [18F]FDG than the viable tumor cells. A maximum of 29% of the glucose utilization was derived from nontumor tissue in this tumor. The comparison of double-tracer autoradiographic distribution patterns of [18F]FDG and [6-3H]-thymidine showed the differences and the similarities between glucose utilization and the DNA synthesis. Whole proliferating tissue metabolizes [18F] FDG but not vice versa. High accumulation of [18F]FDG in the tumor is believed to represent high metabolic activity of the viable tumor cells. Our results showed that one should consider not only the tumor cells proper but also the non-neoplastic cellular elements, which appear in association with growth or necrosis of the tumor cells, for precise analysis of [18F]FDG uptake in tumor-bearing subjects, especially after anti-neoplastic treatment.
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            Tumor volume in pharyngolaryngeal squamous cell carcinoma: comparison at CT, MR imaging, and FDG PET and validation with surgical specimen.

            To compare computed tomography (CT), magnetic resonance (MR) imaging, and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for delineation of gross tumor volume (GTV) in pharyngolaryngeal squamous cell carcinoma and to validate results with the macroscopic surgical specimen when available. Twenty-nine patients with stages II-IV squamous cell carcinoma treated with radiation therapy or chemotherapy and radiation therapy (n = 20) or with total laryngectomy (n = 9) were enrolled. Ten patients had oropharyngeal, 13 had laryngeal, and six had hypopharyngeal tumors. CT, MR imaging, and PET were performed with patients immobilized in a customized thermoplastic mask, and images were coregistered. GTVs obtained with the three modalities were compared quantitatively and qualitatively. If patients underwent total laryngectomy, images were validated with the surgical specimen after three-dimensional coregistration. The effect of each modality was estimated with linear mixed-effects models. Adjustments for multiple comparisons were made with the Bonferonni or Sidak method. For oropharyngeal tumors and for laryngeal or hypopharyngeal tumors, no significant difference (P >.99) was observed between average GTVs delineated at CT (32.0 and 21.4 cm(3), respectively) or MR imaging (27.9 and 21.4 cm(3), respectively), whereas average GTVs at PET were smaller (20.3 [P
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              Diagnostic performance of post-treatment FDG PET or FDG PET/CT imaging in head and neck cancer: a systematic review and meta-analysis.

              Our objective was to conduct a systematic review and meta-analysis of studies assessing the diagnostic performance of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) with or without computed tomography (CT) in post-treatment response assessment and/or surveillance imaging of head and neck squamous cell carcinoma (HNSCC). A systematic search of the indexed medical literature was done using appropriate keywords to identify relevant studies. Metrics of diagnostic test accuracy, viz. sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were extracted from individual studies and combined using a random effects model to yield weighted mean pooled estimates with 95% confidence intervals (95% CI). The impact of timing of post-treatment scan, study quality and advancements in PET technology was explored through meta-regression. A total of 51 studies involving 2,335 patients were included in the meta-analysis. The weighted mean (95% CI) pooled sensitivity, specificity, PPV and NPV of post-treatment FDG PET(CT) for the primary site was 79.9% (73.7-85.2%), 87.5% (85.2-89.5%), 58.6% (52.6-64.5%) and 95.1% (93.5-96.5%), respectively. Similar estimates for the neck were 72.7% (66.6-78.2%), 87.6% (85.7-89.3%), 52.1% (46.6-57.6%) and 94.5% (93.1-95.7%), respectively. Scans done ≥ 12 weeks after completion of definitive therapy had moderately higher diagnostic accuracy on meta-regression analysis using time as a covariate. The overall diagnostic performance of post-treatment FDG PET(CT) for response assessment and surveillance imaging of HNSCC is good, but its PPV is somewhat suboptimal. Its NPV remains exceptionally high and a negative post-treatment scan is highly suggestive of absence of viable disease that can guide therapeutic decision-making. Timing of post-treatment imaging has a significant, though moderate impact on diagnostic accuracy.
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                Author and article information

                Journal
                Acta Otorhinolaryngol Ital
                Acta Otorhinolaryngol Ital
                Pacini
                Acta Otorhinolaryngologica Italica
                Pacini Editore SpA
                0392-100X
                1827-675X
                February 2013
                : 33
                : 1
                : 1-8
                Affiliations
                [1 ] Institute of Nuclear Medicine
                [2 ] Institute of Otolaryngology
                [3 ] Institute of Radiotherapy, Università Cattolica del Sacro Cuore, Rome, Italy
                Author notes
                Address for correspondence: Vittoria Rufini, Istituto di Medicina Nucleare, Università Cattolica del Sacro Cuore, l.go A. Gemelli 8, 00168 Roma, Italy. Tel. +39 06 30154978. Fax +39 06 3058185. E-mail: v.rufini@ 123456rm.unicatt.it
                [*]

                Paola Castaldi and Lucia Leccisotti equally contributed to this paper sharing the first authorship.

                Article
                Pacini
                3631810
                23620633
                dee7f543-537a-4fe4-8773-af82ae42074c
                © Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License, which permits for noncommercial use, distribution, and reproduction in any digital medium, provided the original work is properly cited and is not altered in any way. For details, please refer to http://creativecommons.org/licenses/by-nc-nd/3.0/

                History
                : 1 December 2012
                : 20 December 2012
                Categories
                Review Article

                Otolaryngology
                18f-fdg,pet-ct,carcinoma,squamous cell,head and neck tumours
                Otolaryngology
                18f-fdg, pet-ct, carcinoma, squamous cell, head and neck tumours

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