Evaluation of XRCC1 Gene Polymorphism as a Biomarker in Head and Neck Cancer Patients Undergoing Chemoradiation Therapy
We evaluated the correlation of the x-ray repair cross complementing gene 1 (XRCC1) Arg194Trp polymorphism with clinical outcomes in head and neck squamous cell carcinoma (HNSCC) patients treated with concurrent chemoradiation therapy (CCRT). In this prospective cohort study, we included 101 patient...
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| Veröffentlicht in: | International journal of radiation oncology, biology, physics biology, physics, 2018-07, Vol.101 (3), p.593-601 |
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| creator | Nanda, Sambit Swarup Gandhi, Ajeet Kumar Rastogi, Madhup Khurana, Rohini Hadi, Rahat Sahni, Kamal Mishra, Surendra Prasad Srivastava, Anoop K. Bhatt, Madan Lal Brahma Parmar, Devendra |
| description | We evaluated the correlation of the x-ray repair cross complementing gene 1 (XRCC1) Arg194Trp polymorphism with clinical outcomes in head and neck squamous cell carcinoma (HNSCC) patients treated with concurrent chemoradiation therapy (CCRT).
In this prospective cohort study, we included 101 patients with HNSCC (oral cavity, pharynx, and larynx) who were aged ≥ 18 years, had stage III to IVB disease, had a Karnofsky Performance Status ≥ 80, and were deemed fit for CCRT. DNA extraction was done through polymerase chain reaction, and the genotypes of XRCC1 polymorphism were detected using designed restriction fragment length polymorphism. The genetic polymorphisms were classified into wild and polymorphic variants (Arg194Trp CT and TT). Radiation therapy was delivered with conventional parallel opposed lateral and low anterior neck fields with concurrent weekly cisplatin, 35 mg/m2. Acute toxicity was graded per Radiation Therapy Oncology Group criteria, and treatment response was assessed per World Health Organization criteria. Overall survival and progression-free survival (PFS) were estimated using the Kaplan-Meier method.
Of the patients, 62 had the wild type and 39 had polymorphic variants. Patients with polymorphic variants had higher rates of grade > 2 oral mucositis, with 35.8% versus 16.0% (odds ratio [OR], 2.91; 95% confidence interval [CI], 1.13-7.46; P = .023); dermatitis, with 30.7% versus 8.0% (OR, 5.076; 95% CI, 1.62-15.8; P = .003); and laryngeal toxicity, with 25.6% versus 6.4% (OR, 5; 95% CI, 1.44-17.54; P = .006). Complete response rates in polymorphic versus wild variants were 76.9% versus 56.0% (P = .209). At a median follow-up of 21 months, the 2-year PFS and overall survival rates for patients with polymorphic versus wild variants were 57.0% versus 42.2% (P = .077) and 73.0% versus 55.5% (P = .143), respectively.
Polymorphic variant XRCC1 HNSCC patients treated with CCRT have significantly increased acute radiation morbidities and may have a trend toward better PFS in comparison with the wild variant. |
| doi_str_mv | 10.1016/j.ijrobp.2018.03.039 |
| format | Article |
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In this prospective cohort study, we included 101 patients with HNSCC (oral cavity, pharynx, and larynx) who were aged ≥ 18 years, had stage III to IVB disease, had a Karnofsky Performance Status ≥ 80, and were deemed fit for CCRT. DNA extraction was done through polymerase chain reaction, and the genotypes of XRCC1 polymorphism were detected using designed restriction fragment length polymorphism. The genetic polymorphisms were classified into wild and polymorphic variants (Arg194Trp CT and TT). Radiation therapy was delivered with conventional parallel opposed lateral and low anterior neck fields with concurrent weekly cisplatin, 35 mg/m2. Acute toxicity was graded per Radiation Therapy Oncology Group criteria, and treatment response was assessed per World Health Organization criteria. Overall survival and progression-free survival (PFS) were estimated using the Kaplan-Meier method.
Of the patients, 62 had the wild type and 39 had polymorphic variants. Patients with polymorphic variants had higher rates of grade > 2 oral mucositis, with 35.8% versus 16.0% (odds ratio [OR], 2.91; 95% confidence interval [CI], 1.13-7.46; P = .023); dermatitis, with 30.7% versus 8.0% (OR, 5.076; 95% CI, 1.62-15.8; P = .003); and laryngeal toxicity, with 25.6% versus 6.4% (OR, 5; 95% CI, 1.44-17.54; P = .006). Complete response rates in polymorphic versus wild variants were 76.9% versus 56.0% (P = .209). At a median follow-up of 21 months, the 2-year PFS and overall survival rates for patients with polymorphic versus wild variants were 57.0% versus 42.2% (P = .077) and 73.0% versus 55.5% (P = .143), respectively.
Polymorphic variant XRCC1 HNSCC patients treated with CCRT have significantly increased acute radiation morbidities and may have a trend toward better PFS in comparison with the wild variant.</description><identifier>ISSN: 0360-3016</identifier><identifier>EISSN: 1879-355X</identifier><identifier>DOI: 10.1016/j.ijrobp.2018.03.039</identifier><identifier>PMID: 29893275</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Aged ; BIOLOGICAL MARKERS ; CARCINOMAS ; Chemoradiotherapy - adverse effects ; Cohort Studies ; Disease-Free Survival ; Female ; Genetic Markers - genetics ; Genotype ; HEAD ; Head and Neck Neoplasms - genetics ; Head and Neck Neoplasms - pathology ; Head and Neck Neoplasms - therapy ; Humans ; Male ; Middle Aged ; NECK ; Neoplasm Staging ; PATIENTS ; Polymorphism, Single Nucleotide ; RADIOLOGY AND NUCLEAR MEDICINE ; X-ray Repair Cross Complementing Protein 1 - genetics</subject><ispartof>International journal of radiation oncology, biology, physics, 2018-07, Vol.101 (3), p.593-601</ispartof><rights>2018 Elsevier Inc.</rights><rights>Copyright © 2018 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-33a892377efddc6d9b36de22dc3f69f999a59105bc78934111da2c4598d4a6de3</citedby><cites>FETCH-LOGICAL-c456t-33a892377efddc6d9b36de22dc3f69f999a59105bc78934111da2c4598d4a6de3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S036030161830587X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29893275$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/23073280$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Nanda, Sambit Swarup</creatorcontrib><creatorcontrib>Gandhi, Ajeet Kumar</creatorcontrib><creatorcontrib>Rastogi, Madhup</creatorcontrib><creatorcontrib>Khurana, Rohini</creatorcontrib><creatorcontrib>Hadi, Rahat</creatorcontrib><creatorcontrib>Sahni, Kamal</creatorcontrib><creatorcontrib>Mishra, Surendra Prasad</creatorcontrib><creatorcontrib>Srivastava, Anoop K.</creatorcontrib><creatorcontrib>Bhatt, Madan Lal Brahma</creatorcontrib><creatorcontrib>Parmar, Devendra</creatorcontrib><title>Evaluation of XRCC1 Gene Polymorphism as a Biomarker in Head and Neck Cancer Patients Undergoing Chemoradiation Therapy</title><title>International journal of radiation oncology, biology, physics</title><addtitle>Int J Radiat Oncol Biol Phys</addtitle><description>We evaluated the correlation of the x-ray repair cross complementing gene 1 (XRCC1) Arg194Trp polymorphism with clinical outcomes in head and neck squamous cell carcinoma (HNSCC) patients treated with concurrent chemoradiation therapy (CCRT).
In this prospective cohort study, we included 101 patients with HNSCC (oral cavity, pharynx, and larynx) who were aged ≥ 18 years, had stage III to IVB disease, had a Karnofsky Performance Status ≥ 80, and were deemed fit for CCRT. DNA extraction was done through polymerase chain reaction, and the genotypes of XRCC1 polymorphism were detected using designed restriction fragment length polymorphism. The genetic polymorphisms were classified into wild and polymorphic variants (Arg194Trp CT and TT). Radiation therapy was delivered with conventional parallel opposed lateral and low anterior neck fields with concurrent weekly cisplatin, 35 mg/m2. Acute toxicity was graded per Radiation Therapy Oncology Group criteria, and treatment response was assessed per World Health Organization criteria. Overall survival and progression-free survival (PFS) were estimated using the Kaplan-Meier method.
Of the patients, 62 had the wild type and 39 had polymorphic variants. Patients with polymorphic variants had higher rates of grade > 2 oral mucositis, with 35.8% versus 16.0% (odds ratio [OR], 2.91; 95% confidence interval [CI], 1.13-7.46; P = .023); dermatitis, with 30.7% versus 8.0% (OR, 5.076; 95% CI, 1.62-15.8; P = .003); and laryngeal toxicity, with 25.6% versus 6.4% (OR, 5; 95% CI, 1.44-17.54; P = .006). Complete response rates in polymorphic versus wild variants were 76.9% versus 56.0% (P = .209). At a median follow-up of 21 months, the 2-year PFS and overall survival rates for patients with polymorphic versus wild variants were 57.0% versus 42.2% (P = .077) and 73.0% versus 55.5% (P = .143), respectively.
Polymorphic variant XRCC1 HNSCC patients treated with CCRT have significantly increased acute radiation morbidities and may have a trend toward better PFS in comparison with the wild variant.</description><subject>Adult</subject><subject>Aged</subject><subject>BIOLOGICAL MARKERS</subject><subject>CARCINOMAS</subject><subject>Chemoradiotherapy - adverse effects</subject><subject>Cohort Studies</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Genetic Markers - genetics</subject><subject>Genotype</subject><subject>HEAD</subject><subject>Head and Neck Neoplasms - genetics</subject><subject>Head and Neck Neoplasms - pathology</subject><subject>Head and Neck Neoplasms - therapy</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>NECK</subject><subject>Neoplasm Staging</subject><subject>PATIENTS</subject><subject>Polymorphism, Single Nucleotide</subject><subject>RADIOLOGY AND NUCLEAR MEDICINE</subject><subject>X-ray Repair Cross Complementing Protein 1 - genetics</subject><issn>0360-3016</issn><issn>1879-355X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kFlLAzEUhYMoWpd_IBLweWqW2fIi6OAGokUq-BbS5I5NbZMhGSv996aM-ihcCITvnHvPQeiUkjEltLxYjO0i-Fk3ZoTWY8LTiB00onUlMl4Ub7toRHhJMp7gA3QY44IQQmmV76MDJmrBWVWM0NfNWi0_VW-9w77Fby9NQ_EdOMATv9ysfOjmNq6wiljha-tXKnxAwNbhe1AGK2fwE-gP3Cin0_8kGYHrI351BsK7t-4dN3NINsrYYcl0DkF1m2O016plhJOf9wi93t5Mm_vs8fnuobl6zHRelH3GuaoF41UFrTG6NGLGSwOMGc3bUrRCCFUISoqZrlKinFJqFEtSUZtcJZIfofPB18feyqhtD3quvXOge8k4qTirSaLygdLBxxiglV2wKetGUiK3bcuFHNqW27Yl4WlEkp0Nsu5ztgLzJ_qtNwGXAwAp4tpC2F4AqSpjw_YA4-3_G74BciSS0w</recordid><startdate>20180701</startdate><enddate>20180701</enddate><creator>Nanda, Sambit Swarup</creator><creator>Gandhi, Ajeet Kumar</creator><creator>Rastogi, Madhup</creator><creator>Khurana, Rohini</creator><creator>Hadi, Rahat</creator><creator>Sahni, Kamal</creator><creator>Mishra, Surendra Prasad</creator><creator>Srivastava, Anoop K.</creator><creator>Bhatt, Madan Lal Brahma</creator><creator>Parmar, Devendra</creator><general>Elsevier Inc</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>OTOTI</scope></search><sort><creationdate>20180701</creationdate><title>Evaluation of XRCC1 Gene Polymorphism as a Biomarker in Head and Neck Cancer Patients Undergoing Chemoradiation Therapy</title><author>Nanda, Sambit Swarup ; Gandhi, Ajeet Kumar ; Rastogi, Madhup ; Khurana, Rohini ; Hadi, Rahat ; Sahni, Kamal ; Mishra, Surendra Prasad ; Srivastava, Anoop K. ; Bhatt, Madan Lal Brahma ; Parmar, Devendra</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-33a892377efddc6d9b36de22dc3f69f999a59105bc78934111da2c4598d4a6de3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Aged</topic><topic>BIOLOGICAL MARKERS</topic><topic>CARCINOMAS</topic><topic>Chemoradiotherapy - adverse effects</topic><topic>Cohort Studies</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Genetic Markers - genetics</topic><topic>Genotype</topic><topic>HEAD</topic><topic>Head and Neck Neoplasms - genetics</topic><topic>Head and Neck Neoplasms - pathology</topic><topic>Head and Neck Neoplasms - therapy</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>NECK</topic><topic>Neoplasm Staging</topic><topic>PATIENTS</topic><topic>Polymorphism, Single Nucleotide</topic><topic>RADIOLOGY AND NUCLEAR MEDICINE</topic><topic>X-ray Repair Cross Complementing Protein 1 - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nanda, Sambit Swarup</creatorcontrib><creatorcontrib>Gandhi, Ajeet Kumar</creatorcontrib><creatorcontrib>Rastogi, Madhup</creatorcontrib><creatorcontrib>Khurana, Rohini</creatorcontrib><creatorcontrib>Hadi, Rahat</creatorcontrib><creatorcontrib>Sahni, Kamal</creatorcontrib><creatorcontrib>Mishra, Surendra Prasad</creatorcontrib><creatorcontrib>Srivastava, Anoop K.</creatorcontrib><creatorcontrib>Bhatt, Madan Lal Brahma</creatorcontrib><creatorcontrib>Parmar, Devendra</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>OSTI.GOV</collection><jtitle>International journal of radiation oncology, biology, physics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nanda, Sambit Swarup</au><au>Gandhi, Ajeet Kumar</au><au>Rastogi, Madhup</au><au>Khurana, Rohini</au><au>Hadi, Rahat</au><au>Sahni, Kamal</au><au>Mishra, Surendra Prasad</au><au>Srivastava, Anoop K.</au><au>Bhatt, Madan Lal Brahma</au><au>Parmar, Devendra</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of XRCC1 Gene Polymorphism as a Biomarker in Head and Neck Cancer Patients Undergoing Chemoradiation Therapy</atitle><jtitle>International journal of radiation oncology, biology, physics</jtitle><addtitle>Int J Radiat Oncol Biol Phys</addtitle><date>2018-07-01</date><risdate>2018</risdate><volume>101</volume><issue>3</issue><spage>593</spage><epage>601</epage><pages>593-601</pages><issn>0360-3016</issn><eissn>1879-355X</eissn><abstract>We evaluated the correlation of the x-ray repair cross complementing gene 1 (XRCC1) Arg194Trp polymorphism with clinical outcomes in head and neck squamous cell carcinoma (HNSCC) patients treated with concurrent chemoradiation therapy (CCRT).
In this prospective cohort study, we included 101 patients with HNSCC (oral cavity, pharynx, and larynx) who were aged ≥ 18 years, had stage III to IVB disease, had a Karnofsky Performance Status ≥ 80, and were deemed fit for CCRT. DNA extraction was done through polymerase chain reaction, and the genotypes of XRCC1 polymorphism were detected using designed restriction fragment length polymorphism. The genetic polymorphisms were classified into wild and polymorphic variants (Arg194Trp CT and TT). Radiation therapy was delivered with conventional parallel opposed lateral and low anterior neck fields with concurrent weekly cisplatin, 35 mg/m2. Acute toxicity was graded per Radiation Therapy Oncology Group criteria, and treatment response was assessed per World Health Organization criteria. Overall survival and progression-free survival (PFS) were estimated using the Kaplan-Meier method.
Of the patients, 62 had the wild type and 39 had polymorphic variants. Patients with polymorphic variants had higher rates of grade > 2 oral mucositis, with 35.8% versus 16.0% (odds ratio [OR], 2.91; 95% confidence interval [CI], 1.13-7.46; P = .023); dermatitis, with 30.7% versus 8.0% (OR, 5.076; 95% CI, 1.62-15.8; P = .003); and laryngeal toxicity, with 25.6% versus 6.4% (OR, 5; 95% CI, 1.44-17.54; P = .006). Complete response rates in polymorphic versus wild variants were 76.9% versus 56.0% (P = .209). At a median follow-up of 21 months, the 2-year PFS and overall survival rates for patients with polymorphic versus wild variants were 57.0% versus 42.2% (P = .077) and 73.0% versus 55.5% (P = .143), respectively.
Polymorphic variant XRCC1 HNSCC patients treated with CCRT have significantly increased acute radiation morbidities and may have a trend toward better PFS in comparison with the wild variant.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>29893275</pmid><doi>10.1016/j.ijrobp.2018.03.039</doi><tpages>9</tpages></addata></record> |
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| identifier | ISSN: 0360-3016 |
| ispartof | International journal of radiation oncology, biology, physics, 2018-07, Vol.101 (3), p.593-601 |
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| subjects | Adult Aged BIOLOGICAL MARKERS CARCINOMAS Chemoradiotherapy - adverse effects Cohort Studies Disease-Free Survival Female Genetic Markers - genetics Genotype HEAD Head and Neck Neoplasms - genetics Head and Neck Neoplasms - pathology Head and Neck Neoplasms - therapy Humans Male Middle Aged NECK Neoplasm Staging PATIENTS Polymorphism, Single Nucleotide RADIOLOGY AND NUCLEAR MEDICINE X-ray Repair Cross Complementing Protein 1 - genetics |
| title | Evaluation of XRCC1 Gene Polymorphism as a Biomarker in Head and Neck Cancer Patients Undergoing Chemoradiation Therapy |
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