{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:06:34Z","timestamp":1791547594462,"version":"4.3.4"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T00:00:00Z","timestamp":1573689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T00:00:00Z","timestamp":1573689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"LSH-TKI Foundation","award":["LSHM15036"],"award-info":[{"award-number":["LSHM15036"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The majority of patients with head and neck squamous cell carcinoma (HNSCC) receive bilateral elective nodal irradiation (ENI), in order to reduce the risk of regional failure. Bilateral ENI, as compared to unilateral ENI, is associated with higher incidence of acute and late radiation-induced toxicity with subsequent deterioration of quality of life. Increasing evidence that the incidence of contralateral regional failure (cRF) in lateralized HNSCC is very low (&lt;\u200910%) suggests that it can be justified to treat selected patients unilaterally. This trial aims to minimize the proportion of patients that undergo bilateral ENI, by using lymph drainage mapping by SPECT\/CT to select patients with a minimal risk of contralateral nodal failure for unilateral elective nodal irradiation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In this one-armed, single-center prospective trial, patients with primary T1-4\u2009N0-2b HNSCC of the oral cavity, oropharynx, larynx (except T1 glottic) or hypopharynx, not extending beyond the midline and planned for primary (chemo) radiotherapy, are eligible. After <jats:sup>99m<\/jats:sup>Tc-nanocolloid tracer injection in and around the tumor, lymphatic drainage is visualized using SPECT\/CT. In case of contralateral lymph drainage, a contralateral sentinel node procedure is performed on the same day. Patients without contralateral lymph drainage, and patients with contralateral drainage but without pathologic involvement of any removed contralateral sentinel nodes, receive unilateral ENI. Only when tumor cells are found in a contralateral sentinel node the patient will be treated with bilateral ENI. The primary endpoint is cumulative incidence of cRF at 1 and 2\u2009years after treatment. Secondary endpoints are radiation-related toxicity and quality of life. The removed lymph nodes will be studied to determine the prevalence of occult metastatic disease in contralateral sentinel nodes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>This single-center prospective trial aims to reduce the incidence and duration of radiation-related toxicities and improve quality of life of HNSCC patients, by using lymph drainage mapping by SPECT\/CT to select patients with a minimal risk of contralateral nodal failure for unilateral elective nodal irradiation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03968679?term=NCT03968679&amp;draw=1&amp;rank=1\">NCT03968679<\/jats:ext-link>, date of registration: May 30, 2019.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12885-019-6331-8","type":"journal-article","created":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T14:03:10Z","timestamp":1573740190000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Mapping of sentinel lymph node drainage using SPECT\/CT to tailor elective nodal irradiation in head and neck cancer patients (SUSPECT-2): a single-center prospective trial"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0894-1510","authenticated-orcid":false,"given":"Pieter D.","family":"de Veij Mestdagh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem H.","family":"Schreuder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter V.","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten L.","family":"Donswijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"van Werkhoven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline E.","family":"van der Wal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Dirven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baris","family":"Karakullukcu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Jakob","family":"Sonke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel W. M.","family":"van den Brekel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corrie A. M.","family":"Marijnen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abrahim","family":"Al-Mamgani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,14]]},"reference":[{"key":"6331_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejca.2017.05.035","volume":"82","author":"A Al-Mamgani","year":"2017","unstructured":"Al-Mamgani A, Verheij M, van den Brekel MWM. Elective unilateral nodal irradiation in head and neck squamous cell carcinoma: a paradigm shift. Eur J Cancer. 2017;82:1\u20135. https:\/\/doi.org\/10.1016\/j.ejca.2017.05.035.","journal-title":"Eur J Cancer"},{"key":"6331_CR2","doi-asserted-by":"publisher","first-page":"2777","DOI":"10.1016\/j.ejca.2015.08.023","volume":"51","author":"C Schilling","year":"2015","unstructured":"Schilling C, Stoeckli SJ, Haerle SK, Broglie MA, Huber GF, Sorensen JA, et al. Sentinel European node trial (SENT): 3-year results of sentinel node biopsy in oral cancer. Eur J Cancer. 2015;51:2777\u201384.","journal-title":"Eur J Cancer"},{"key":"6331_CR3","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1002\/hed.20062","volume":"26","author":"JA Werner","year":"2004","unstructured":"Werner JA, D\u00fcnne AA, Ramaswamy A, Dalchow C, Behr T, Moll R, et al. The sentinel node concept in head and neck cancer: solution for the controversies in the NO neck? Head Neck. 2004;26:603\u201311.","journal-title":"Head Neck"},{"key":"6331_CR4","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1038\/sj.bjc.6601877","volume":"91","author":"S H\u00f6ft","year":"2004","unstructured":"H\u00f6ft S, Maune S, Muhle C, Brenner W, Czech N, Kampen WU, et al. Sentinel lymph-node biopsy in head and neck cancer. Br J Cancer. 2004;91:124\u20138.","journal-title":"Br J Cancer"},{"key":"6331_CR5","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.1002\/lary.21131","volume":"120","author":"G Lawson","year":"2010","unstructured":"Lawson G, Matar N, Nollevaux MC, Jamart J, Krug B, Delos M, et al. Reliability of sentinel node technique in the treatment of N0 supraglottic laryngeal cancer. Laryngoscope. 2010;120:2213\u20137.","journal-title":"Laryngoscope."},{"key":"6331_CR6","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1002\/hed.23297","volume":"36","author":"C Liu","year":"2014","unstructured":"Liu C, Dutu G, Peters LJ, Rischin D, Corry J. Tonsillar cancer: the Peter MacCallum experience with unilateral and bilateral irradiation. Head Neck. 2014;36:317\u201322. https:\/\/doi.org\/10.1002\/hed.23297.","journal-title":"Head Neck."},{"key":"6331_CR7","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.radonc.2007.06.005","volume":"85","author":"K Jensen","year":"2007","unstructured":"Jensen K, Overgaard M, Grau C. Morbidity after ipsilateral radiotherapy for oropharyngeal cancer. Radiother Oncol. 2007;85:90\u20137.","journal-title":"Radiother Oncol"},{"key":"6331_CR8","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/S1470-2045(10)70290-4","volume":"12","author":"CM Nutting","year":"2011","unstructured":"Nutting CM, Morden JP, Harrington KJ, Urbano TG, Bhide SA, Clark C, et al. Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2011;12:127\u201336.","journal-title":"Lancet Oncol"},{"key":"6331_CR9","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.radonc.2007.03.002","volume":"85","author":"AP Jellema","year":"2007","unstructured":"Jellema AP, Slotman BJ, Doornaert P, Leemans CR, Langendijk JA. Unilateral versus bilateral irradiation in squamous cell head and neck cancer in relation to patient-rated xerostomia and sticky saliva. Radiother Oncol. 2007;85:83\u20139.","journal-title":"Radiother Oncol"},{"key":"6331_CR10","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.radonc.2012.12.014","volume":"106","author":"A Al-Mamgani","year":"2013","unstructured":"Al-Mamgani A, Van Rooij P, Tans L, Verduijn GM, Sewnaik A, De Jong RJB. A prospective evaluation of patient-reported quality-of-life after (chemo) radiation for oropharyngeal cancer: which patients are at risk of significant quality-of-life deterioration? Radiother Oncol. 2013;106:359\u201363. https:\/\/doi.org\/10.1016\/j.radonc.2012.12.014.","journal-title":"Radiother Oncol"},{"key":"6331_CR11","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.ctrv.2009.08.008","volume":"35","author":"K Manikantan","year":"2009","unstructured":"Manikantan K, Khode S, Sayed SI, Roe J, Nutting CM, Rhys-Evans P, et al. Dysphagia in head and neck cancer. Cancer Treat Rev. 2009;35:724\u201332. https:\/\/doi.org\/10.1016\/j.ctrv.2009.08.008.","journal-title":"Cancer Treat Rev"},{"key":"6331_CR12","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.1007\/s00405-018-5050-0","volume":"275","author":"PD de Veij Mestdagh","year":"2018","unstructured":"de Veij Mestdagh PD, Jonker MCJ, Vogel WV, Schreuder WH, Donswijk ML, Klop WMC, et al. SPECT\/CT-guided lymph drainage mapping for the planning of unilateral elective nodal irradiation in head and neck squamous cell carcinoma. Eur Arch Oto-Rhino-Laryngology. 2018;275:2135\u201344. https:\/\/doi.org\/10.1007\/s00405-018-5050-0.","journal-title":"Eur Arch Oto-Rhino-Laryngology"},{"key":"6331_CR13","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.radonc.2018.07.023","volume":"130","author":"PD de Veij Mestdagh","year":"2019","unstructured":"de Veij Mestdagh PD, Janssen T, Lamers E, Carbaat C, Hamming-Vrieze O, Vogel WV, et al. SPECT\/CT-guided elective nodal irradiation for head and neck cancer: estimation of clinical benefits using NTCP models. Radiother Oncol. 2019;130:18\u201324. https:\/\/doi.org\/10.1016\/j.radonc.2018.07.023.","journal-title":"Radiother Oncol"},{"key":"6331_CR14","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1016\/j.oraloncology.2014.07.020","volume":"50","author":"GB Flach","year":"2014","unstructured":"Flach GB, Bloemena E, Klop WM, van Es RJ, Schepman KP, Hoekstra OS, et al. Sentinel lymph node biopsy in clinically N0 T1-T2 staged oral cancer: the Dutch multicenter trial. Oral Oncol. 2014;50:1020\u20134.","journal-title":"Oral Oncol"},{"key":"6331_CR15","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1097\/MLG.0b013e318093ee67","volume":"117","author":"SJ Stoeckli","year":"2007","unstructured":"Stoeckli SJ. Sentinel node biopsy for Oral and Oropharyngeal squamous cell carcinoma of the head and neck. Laryngoscope. 2007;117:1539\u201351. https:\/\/doi.org\/10.1097\/MLG.0b013e318093ee67.","journal-title":"Laryngoscope."},{"key":"6331_CR16","doi-asserted-by":"publisher","first-page":"2568","DOI":"10.1245\/s10434-008-0008-x","volume":"15","author":"M Tomifuji","year":"2008","unstructured":"Tomifuji M, Shiotani A, Fujii H, Araki K, Saito K, Inagaki K, et al. Sentinel node concept in clinically n0 laryngeal and hypopharyngeal cancer. Ann Surg Oncol. 2008;15:2568\u201375.","journal-title":"Ann Surg Oncol"},{"key":"6331_CR17","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.radonc.2013.10.010","volume":"110","author":"V Gr\u00e9goire","year":"2014","unstructured":"Gr\u00e9goire V, Ang K, Budach W, Grau C, Hamoir M, Langendijk JA, et al. Delineation of the neck node levels for head and neck tumors: a 2013 update. DAHANCA, EORTC, HKNPCSG, NCIC CTG, NCRI, RTOG, TROG consensus guidelines. Radiother Oncol. 2014;110:172\u201381.","journal-title":"Radiother Oncol"},{"key":"6331_CR18","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.radonc.2015.07.041","volume":"117","author":"CL Brouwer","year":"2015","unstructured":"Brouwer CL, Steenbakkers RJHM, Bourhis J, Budach W, Grau C, Gr\u00e9goire V, et al. CT-based delineation of organs at risk in the head and neck region: DAHANCA, EORTC, GORTEC, HKNPCSG, NCIC CTG, NCRI, NRG oncology and TROG consensus guidelines. Radiother Oncol. 2015;117:83\u201390. https:\/\/doi.org\/10.1016\/j.radonc.2015.07.041.","journal-title":"Radiother Oncol"},{"key":"6331_CR19","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1016\/j.ijrobp.2008.10.023","volume":"74","author":"KE Rusthoven","year":"2009","unstructured":"Rusthoven KE, Raben D, Schneider C, Witt R, Sammons S, Raben A. Freedom from local and regional failure of contralateral neck with ipsilateral neck radiotherapy for node-positive tonsil cancer: results of a prospective management approach. Int J Radiat Oncol Biol Phys. 2009;74:1365\u201370. https:\/\/doi.org\/10.1016\/j.ijrobp.2008.10.023.","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"6331_CR20","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.ijrobp.2011.06.1975","volume":"83","author":"GM Chronowski","year":"2012","unstructured":"Chronowski GM, Garden AS, Morrison WH, Frank SJ, Schwartz DL, Shah SJ, et al. Unilateral radiotherapy for the treatment of tonsil cancer. Int J Radiat Oncol Biol Phys. 2012;83:204\u20139. https:\/\/doi.org\/10.1016\/j.ijrobp.2011.06.1975.","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"6331_CR21","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.radonc.2012.12.006","volume":"106","author":"A Al-Mamgani","year":"2013","unstructured":"Al-Mamgani A, Van Rooij P, Fransen D, Levendag P. Unilateral neck irradiation for well-lateralized oropharyngeal cancer. Radiother Oncol. 2013;106:69\u201373. https:\/\/doi.org\/10.1016\/j.radonc.2012.12.006.","journal-title":"Radiother Oncol"},{"key":"6331_CR22","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/0167-8140(89)90167-9","volume":"14","author":"WM Mendenhall","year":"1989","unstructured":"Mendenhall WM, Parsons JT, Brant TA, Stringer SP, Cassisi NJ, Million RR. Is elective neck treatment indicated for T2N0 squamous cell carcinoma of the glottic larynx? Radiother Oncol. 1989;14:199\u2013202 http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/2710950.","journal-title":"Radiother Oncol"},{"key":"6331_CR23","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1001\/archotol.1990.01870070078014","volume":"116","author":"D Howell-Burke","year":"1990","unstructured":"Howell-Burke D, Peters LJ, Goepfert H, Oswald MJ. T2 glottic cancer. Recurrence, salvage, and survival after definitive radiotherapy. Arch Otolaryngol Head Neck Surg. 1990;116:830\u20135 http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/2363922.","journal-title":"Arch Otolaryngol Head Neck Surg"},{"key":"6331_CR24","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1001\/archotol.126.3.360","volume":"126","author":"CJ O\u2019Brien","year":"2000","unstructured":"O\u2019Brien CJ, Traynor SJ, McNeil E, McMahon JD, Chaplin JM. The use of clinical criteria alone in the Management of the Clinically Negative Neck among Patients with Squamous Cell Carcinoma of the Oral cavity and oropharynx. Arch Otolaryngol Neck Surg. 2000;126:360. https:\/\/doi.org\/10.1001\/archotol.126.3.360.","journal-title":"Arch Otolaryngol Neck Surg"}],"container-title":["BMC Cancer"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-019-6331-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12885-019-6331-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-019-6331-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T00:07:26Z","timestamp":1605226046000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccancer.biomedcentral.com\/articles\/10.1186\/s12885-019-6331-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,14]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["6331"],"URL":"https:\/\/doi.org\/10.1186\/s12885-019-6331-8","relation":{},"ISSN":["1471-2407"],"issn-type":[{"value":"1471-2407","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,14]]},"assertion":[{"value":"9 August 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 November 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study ( Identifier NCT03968679) will be conducted in accordance with the Declaration of Helsinki and the ICH Harmonized Tripartite Guideline for Good Clinical Practice. The study has been approved by the local research ethics committee (Medical Research Ethics Committee of the Netherlands Cancer Institute\/Antoni van Leeuwenhoek, protocol ID: NL68958.031.19). All patients are given oral and written information about the study, and are given sufficient time to consider participating. Written informed consent must be obtained from each patient before inclusion.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1110"}}