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Pattern of radiation-induced thyroid gland changes in nasopharyngeal carcinoma patients in 48 months after radiotherapy
Radiation-induced hypothyroidism is the most common thyroid disorder after radiotherapy in nasopharyngeal carcinoma (NPC) patients. This study evaluated the pattern of radiation-induced thyroid gland changes in 48 months after radiotherapy in NPC patients and the association of hypothyroidism incide...
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Published in: | PloS one 2018-07, Vol.13 (7), p.e0200310 |
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description | Radiation-induced hypothyroidism is the most common thyroid disorder after radiotherapy in nasopharyngeal carcinoma (NPC) patients. This study evaluated the pattern of radiation-induced thyroid gland changes in 48 months after radiotherapy in NPC patients and the association of hypothyroidism incidence with thyroid dose.
Fifty-six NPC patients treated by intensity modulated radiotherapy in 2013 were recruited. All patients received baseline thyroid hormones (fT3, fT4 and TSH) tests and CT scan before radiotherapy. Repeated measures of the thyroid hormones and gland volume were performed at 3, 6, 12, 18, 24, 30, 36 and 48 months after treatment. Trend lines of the thyroid volume and hormone level changes against time were plotted. The incidence of hypothyroidism patients and its relationship with the dose were also evaluated.
The mean thyroid volume followed a decreasing trend after radiotherapy, reaching a minimum (-39.8%) at 30 months and slightly increased afterward. The fT4 level followed a similar pattern with its mean value dropped by 21.5% at 30 months and became steady after 36 months. TSH level showed gradual rise from just after radiotherapy, reaching a peak at 24 months and became relatively steady after 36 months. The incidence of hypothyroidism increased to a maximum at 24 months (28.6%) and dropped afterwards. Thyroid Dmean and D50 were significantly correlated with hypothyroidism incidence in 12 to 30 months (ρ > 0.40, p < 0.05).
The patterns of radiation induced thyroid volume shrinkage and fT4 level reduction were similar, with both of them showed decreasing trend from 0 to 30 months. The thyroid volume and function reached a relatively steady state after 36 months. The incidence of hypothyroidism increased up to 24 months and its frequency was associated with the thyroid dose. |
doi_str_mv | 10.1371/journal.pone.0200310 |
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Fifty-six NPC patients treated by intensity modulated radiotherapy in 2013 were recruited. All patients received baseline thyroid hormones (fT3, fT4 and TSH) tests and CT scan before radiotherapy. Repeated measures of the thyroid hormones and gland volume were performed at 3, 6, 12, 18, 24, 30, 36 and 48 months after treatment. Trend lines of the thyroid volume and hormone level changes against time were plotted. The incidence of hypothyroidism patients and its relationship with the dose were also evaluated.
The mean thyroid volume followed a decreasing trend after radiotherapy, reaching a minimum (-39.8%) at 30 months and slightly increased afterward. The fT4 level followed a similar pattern with its mean value dropped by 21.5% at 30 months and became steady after 36 months. TSH level showed gradual rise from just after radiotherapy, reaching a peak at 24 months and became relatively steady after 36 months. The incidence of hypothyroidism increased to a maximum at 24 months (28.6%) and dropped afterwards. Thyroid Dmean and D50 were significantly correlated with hypothyroidism incidence in 12 to 30 months (ρ > 0.40, p < 0.05).
The patterns of radiation induced thyroid volume shrinkage and fT4 level reduction were similar, with both of them showed decreasing trend from 0 to 30 months. The thyroid volume and function reached a relatively steady state after 36 months. The incidence of hypothyroidism increased up to 24 months and its frequency was associated with the thyroid dose.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0200310</identifier><identifier>PMID: 29985952</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Analysis ; Biology and Life Sciences ; Cancer patients ; Cancer therapies ; Care and treatment ; Computed tomography ; Female ; Follow-Up Studies ; Head & neck cancer ; Hormones ; Hospitals ; Humans ; Hypothyroidism ; Hypothyroidism - blood ; Hypothyroidism - epidemiology ; Hypothyroidism - etiology ; Incidence ; Informatics ; Lymphatic system ; Male ; Medicine and Health Sciences ; Middle Aged ; Nasopharyngeal cancer ; Nasopharyngeal carcinoma ; Nasopharyngeal Carcinoma - blood ; Nasopharyngeal Carcinoma - pathology ; Nasopharyngeal Carcinoma - radiotherapy ; Nasopharyngeal Neoplasms - blood ; Nasopharyngeal Neoplasms - pathology ; Nasopharyngeal Neoplasms - radiotherapy ; Patients ; Quality of life ; Radiation ; Radiation effects ; Radiation Injuries - blood ; Radiation Injuries - epidemiology ; Radiation Injuries - etiology ; Radiation therapy ; Radiotherapy ; Radiotherapy - adverse effects ; Radiotherapy Dosage ; Shrinkage ; Throat cancer ; Thyroid ; Thyroid diseases ; Thyroid gland ; Thyroid Gland - pathology ; Thyroid Gland - radiation effects ; Thyroid hormones ; Thyroid-stimulating hormone ; Thyrotropin - blood ; Thyroxine - blood ; Triiodothyronine - blood</subject><ispartof>PloS one, 2018-07, Vol.13 (7), p.e0200310</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Lin et al 2018 Lin et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-a1c78f9d921e9d3b9825bf770c1674ba339f6611e07a5a5ffbb454dd8eea344c3</citedby><cites>FETCH-LOGICAL-c692t-a1c78f9d921e9d3b9825bf770c1674ba339f6611e07a5a5ffbb454dd8eea344c3</cites><orcidid>0000-0002-1257-4154</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2067603315/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2067603315?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29985952$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Zhang, Qinghui</contributor><creatorcontrib>Lin, Zhixiong</creatorcontrib><creatorcontrib>Yang, Zhining</creatorcontrib><creatorcontrib>He, Binghui</creatorcontrib><creatorcontrib>Wang, Dangdang</creatorcontrib><creatorcontrib>Gao, Xiaoyin</creatorcontrib><creatorcontrib>Tam, Shing-Yau</creatorcontrib><creatorcontrib>Wu, Vincent Wing Cheung</creatorcontrib><title>Pattern of radiation-induced thyroid gland changes in nasopharyngeal carcinoma patients in 48 months after radiotherapy</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Radiation-induced hypothyroidism is the most common thyroid disorder after radiotherapy in nasopharyngeal carcinoma (NPC) patients. This study evaluated the pattern of radiation-induced thyroid gland changes in 48 months after radiotherapy in NPC patients and the association of hypothyroidism incidence with thyroid dose.
Fifty-six NPC patients treated by intensity modulated radiotherapy in 2013 were recruited. All patients received baseline thyroid hormones (fT3, fT4 and TSH) tests and CT scan before radiotherapy. Repeated measures of the thyroid hormones and gland volume were performed at 3, 6, 12, 18, 24, 30, 36 and 48 months after treatment. Trend lines of the thyroid volume and hormone level changes against time were plotted. The incidence of hypothyroidism patients and its relationship with the dose were also evaluated.
The mean thyroid volume followed a decreasing trend after radiotherapy, reaching a minimum (-39.8%) at 30 months and slightly increased afterward. The fT4 level followed a similar pattern with its mean value dropped by 21.5% at 30 months and became steady after 36 months. TSH level showed gradual rise from just after radiotherapy, reaching a peak at 24 months and became relatively steady after 36 months. The incidence of hypothyroidism increased to a maximum at 24 months (28.6%) and dropped afterwards. Thyroid Dmean and D50 were significantly correlated with hypothyroidism incidence in 12 to 30 months (ρ > 0.40, p < 0.05).
The patterns of radiation induced thyroid volume shrinkage and fT4 level reduction were similar, with both of them showed decreasing trend from 0 to 30 months. The thyroid volume and function reached a relatively steady state after 36 months. The incidence of hypothyroidism increased up to 24 months and its frequency was associated with the thyroid dose.</description><subject>Adult</subject><subject>Aged</subject><subject>Analysis</subject><subject>Biology and Life Sciences</subject><subject>Cancer patients</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Computed tomography</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Head & neck cancer</subject><subject>Hormones</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Hypothyroidism</subject><subject>Hypothyroidism - blood</subject><subject>Hypothyroidism - epidemiology</subject><subject>Hypothyroidism - etiology</subject><subject>Incidence</subject><subject>Informatics</subject><subject>Lymphatic system</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Nasopharyngeal cancer</subject><subject>Nasopharyngeal carcinoma</subject><subject>Nasopharyngeal Carcinoma - blood</subject><subject>Nasopharyngeal Carcinoma - pathology</subject><subject>Nasopharyngeal Carcinoma - radiotherapy</subject><subject>Nasopharyngeal Neoplasms - blood</subject><subject>Nasopharyngeal Neoplasms - pathology</subject><subject>Nasopharyngeal Neoplasms - radiotherapy</subject><subject>Patients</subject><subject>Quality of life</subject><subject>Radiation</subject><subject>Radiation effects</subject><subject>Radiation Injuries - blood</subject><subject>Radiation Injuries - epidemiology</subject><subject>Radiation Injuries - etiology</subject><subject>Radiation therapy</subject><subject>Radiotherapy</subject><subject>Radiotherapy - adverse effects</subject><subject>Radiotherapy Dosage</subject><subject>Shrinkage</subject><subject>Throat cancer</subject><subject>Thyroid</subject><subject>Thyroid diseases</subject><subject>Thyroid gland</subject><subject>Thyroid Gland - pathology</subject><subject>Thyroid Gland - radiation effects</subject><subject>Thyroid hormones</subject><subject>Thyroid-stimulating hormone</subject><subject>Thyrotropin - blood</subject><subject>Thyroxine - blood</subject><subject>Triiodothyronine - blood</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNktuL1DAUxoso7jr6H4gWBMGHGXPpLS_CsngZWFjx9hpOk7TN0ibdJFXnvzcz012moCB5SDj5nS8nH1-SPMdog2mJ397YyRnoN6M1aoMIQhSjB8k5ZpSsC4Low5PzWfLE-xuEcloVxePkjDBW5Swn58mvzxCCcia1TepAagjamrU2chJKpqHbOatl2vZgZCo6MK3yqTapAW_HDtwuFqBPBTihjR0gHaOAMuEAZVU6WBM6n0IT3zjo29ApB-PuafKogd6rZ_O-Sr5_eP_t8tP66vrj9vLiai0KRsIasCirhklGsGKS1qwied2UJRK4KLMaKGVNUWCsUAk55E1T11meSVkpBTTLBF0lL4-6Y289nz3znKCiLBClOI_E9khICzd8dHqI3-IWND8UrGs5uKBFr7jCRFaYEFYUWVbFqaoGBFVlLbGoAUPUeje_NtWDkiI64aBfiC5vjO54a3_yOEtJ8yoKvJoFnL2dlA__GHmmWohTadPYKCYG7QW_yLOcVbSK4CrZ_IWKS6pBi5iaRsf6ouHNoiEyQf0OLUze8-3XL__PXv9Ysq9P2C4GJmbC9tM-an4JZkdQOOu9U829cxjxfejv3OD70PM59LHtxanr9013Kad_AH8Y_to</recordid><startdate>20180709</startdate><enddate>20180709</enddate><creator>Lin, Zhixiong</creator><creator>Yang, Zhining</creator><creator>He, Binghui</creator><creator>Wang, Dangdang</creator><creator>Gao, Xiaoyin</creator><creator>Tam, Shing-Yau</creator><creator>Wu, Vincent Wing Cheung</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-1257-4154</orcidid></search><sort><creationdate>20180709</creationdate><title>Pattern of radiation-induced thyroid gland changes in nasopharyngeal carcinoma patients in 48 months after radiotherapy</title><author>Lin, Zhixiong ; Yang, Zhining ; He, Binghui ; Wang, Dangdang ; Gao, Xiaoyin ; Tam, Shing-Yau ; Wu, Vincent Wing Cheung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-a1c78f9d921e9d3b9825bf770c1674ba339f6611e07a5a5ffbb454dd8eea344c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Analysis</topic><topic>Biology and Life Sciences</topic><topic>Cancer patients</topic><topic>Cancer therapies</topic><topic>Care and treatment</topic><topic>Computed tomography</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Head & neck cancer</topic><topic>Hormones</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Hypothyroidism</topic><topic>Hypothyroidism - blood</topic><topic>Hypothyroidism - epidemiology</topic><topic>Hypothyroidism - etiology</topic><topic>Incidence</topic><topic>Informatics</topic><topic>Lymphatic system</topic><topic>Male</topic><topic>Medicine and Health Sciences</topic><topic>Middle Aged</topic><topic>Nasopharyngeal cancer</topic><topic>Nasopharyngeal carcinoma</topic><topic>Nasopharyngeal Carcinoma - blood</topic><topic>Nasopharyngeal Carcinoma - pathology</topic><topic>Nasopharyngeal Carcinoma - radiotherapy</topic><topic>Nasopharyngeal Neoplasms - blood</topic><topic>Nasopharyngeal Neoplasms - pathology</topic><topic>Nasopharyngeal Neoplasms - radiotherapy</topic><topic>Patients</topic><topic>Quality of life</topic><topic>Radiation</topic><topic>Radiation effects</topic><topic>Radiation Injuries - blood</topic><topic>Radiation Injuries - epidemiology</topic><topic>Radiation Injuries - etiology</topic><topic>Radiation therapy</topic><topic>Radiotherapy</topic><topic>Radiotherapy - adverse effects</topic><topic>Radiotherapy Dosage</topic><topic>Shrinkage</topic><topic>Throat cancer</topic><topic>Thyroid</topic><topic>Thyroid diseases</topic><topic>Thyroid gland</topic><topic>Thyroid Gland - pathology</topic><topic>Thyroid Gland - radiation effects</topic><topic>Thyroid hormones</topic><topic>Thyroid-stimulating hormone</topic><topic>Thyrotropin - blood</topic><topic>Thyroxine - blood</topic><topic>Triiodothyronine - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lin, Zhixiong</creatorcontrib><creatorcontrib>Yang, Zhining</creatorcontrib><creatorcontrib>He, Binghui</creatorcontrib><creatorcontrib>Wang, Dangdang</creatorcontrib><creatorcontrib>Gao, Xiaoyin</creatorcontrib><creatorcontrib>Tam, Shing-Yau</creatorcontrib><creatorcontrib>Wu, Vincent Wing Cheung</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale_Opposing Viewpoints In Context</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest - 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This study evaluated the pattern of radiation-induced thyroid gland changes in 48 months after radiotherapy in NPC patients and the association of hypothyroidism incidence with thyroid dose.
Fifty-six NPC patients treated by intensity modulated radiotherapy in 2013 were recruited. All patients received baseline thyroid hormones (fT3, fT4 and TSH) tests and CT scan before radiotherapy. Repeated measures of the thyroid hormones and gland volume were performed at 3, 6, 12, 18, 24, 30, 36 and 48 months after treatment. Trend lines of the thyroid volume and hormone level changes against time were plotted. The incidence of hypothyroidism patients and its relationship with the dose were also evaluated.
The mean thyroid volume followed a decreasing trend after radiotherapy, reaching a minimum (-39.8%) at 30 months and slightly increased afterward. The fT4 level followed a similar pattern with its mean value dropped by 21.5% at 30 months and became steady after 36 months. TSH level showed gradual rise from just after radiotherapy, reaching a peak at 24 months and became relatively steady after 36 months. The incidence of hypothyroidism increased to a maximum at 24 months (28.6%) and dropped afterwards. Thyroid Dmean and D50 were significantly correlated with hypothyroidism incidence in 12 to 30 months (ρ > 0.40, p < 0.05).
The patterns of radiation induced thyroid volume shrinkage and fT4 level reduction were similar, with both of them showed decreasing trend from 0 to 30 months. The thyroid volume and function reached a relatively steady state after 36 months. The incidence of hypothyroidism increased up to 24 months and its frequency was associated with the thyroid dose.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29985952</pmid><doi>10.1371/journal.pone.0200310</doi><orcidid>https://orcid.org/0000-0002-1257-4154</orcidid><oa>free_for_read</oa></addata></record> |
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recordid | cdi_plos_journals_2067603315 |
source | Publicly Available Content Database (Proquest) (PQ_SDU_P3); PubMed Central |
subjects | Adult Aged Analysis Biology and Life Sciences Cancer patients Cancer therapies Care and treatment Computed tomography Female Follow-Up Studies Head & neck cancer Hormones Hospitals Humans Hypothyroidism Hypothyroidism - blood Hypothyroidism - epidemiology Hypothyroidism - etiology Incidence Informatics Lymphatic system Male Medicine and Health Sciences Middle Aged Nasopharyngeal cancer Nasopharyngeal carcinoma Nasopharyngeal Carcinoma - blood Nasopharyngeal Carcinoma - pathology Nasopharyngeal Carcinoma - radiotherapy Nasopharyngeal Neoplasms - blood Nasopharyngeal Neoplasms - pathology Nasopharyngeal Neoplasms - radiotherapy Patients Quality of life Radiation Radiation effects Radiation Injuries - blood Radiation Injuries - epidemiology Radiation Injuries - etiology Radiation therapy Radiotherapy Radiotherapy - adverse effects Radiotherapy Dosage Shrinkage Throat cancer Thyroid Thyroid diseases Thyroid gland Thyroid Gland - pathology Thyroid Gland - radiation effects Thyroid hormones Thyroid-stimulating hormone Thyrotropin - blood Thyroxine - blood Triiodothyronine - blood |
title | Pattern of radiation-induced thyroid gland changes in nasopharyngeal carcinoma patients in 48 months after radiotherapy |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-02T10%3A22%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Pattern%20of%20radiation-induced%20thyroid%20gland%20changes%20in%20nasopharyngeal%20carcinoma%20patients%20in%2048%20months%20after%20radiotherapy&rft.jtitle=PloS%20one&rft.au=Lin,%20Zhixiong&rft.date=2018-07-09&rft.volume=13&rft.issue=7&rft.spage=e0200310&rft.pages=e0200310-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0200310&rft_dat=%3Cgale_plos_%3EA545983803%3C/gale_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c692t-a1c78f9d921e9d3b9825bf770c1674ba339f6611e07a5a5ffbb454dd8eea344c3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2067603315&rft_id=info:pmid/29985952&rft_galeid=A545983803&rfr_iscdi=true |