4π Non-Coplanar Liver SBRT: A Novel Delivery Technique

Purpose To improve the quality of liver stereotactic body radiation therapy (SBRT) treatments, a novel 4π framework was developed with accompanying algorithms to optimize non-coplanar beam orientations and fluences. The dose optimization is performed on a patient-specific deliverable beam geometry s...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:International journal of radiation oncology, biology, physics biology, physics, 2013-04, Vol.85 (5), p.1360-1366
Hauptverfasser: Dong, Peng, PhD, Lee, Percy, MD, Ruan, Dan, PhD, Long, Troy, BS, Romeijn, Edwin, PhD, Yang, Yingli, PhD, Low, Daniel, PhD, Kupelian, Patrick, MD, Sheng, Ke, PhD
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 1366
container_issue 5
container_start_page 1360
container_title International journal of radiation oncology, biology, physics
container_volume 85
creator Dong, Peng, PhD
Lee, Percy, MD
Ruan, Dan, PhD
Long, Troy, BS
Romeijn, Edwin, PhD
Yang, Yingli, PhD
Low, Daniel, PhD
Kupelian, Patrick, MD
Sheng, Ke, PhD
description Purpose To improve the quality of liver stereotactic body radiation therapy (SBRT) treatments, a novel 4π framework was developed with accompanying algorithms to optimize non-coplanar beam orientations and fluences. The dose optimization is performed on a patient-specific deliverable beam geometry solution space, parameterized with patient and linear accelerator gantry orientations. Methods and Materials Beams causing collision between the gantry and the couch or patient were eliminated by simulating all beam orientations using a precise computer assisted design model of the linear accelerator and a human subject. Integrated beam orientation and fluence map optimizations were performed on remaining beams using a greedy column generation method. Testing of the new method was performed on 10 liver SBRT cases previously treated with 50 to 60 Gy in 5 fractions using volumetric modulated arc therapy (VMAT). For each patient, both 14 and 22 non-coplanar fields were selected and optimized to meet the objective of ≥95% of the planning target volume (PTV) covered by 100% of the prescription dose. Doses to organs at risk, normal liver volumes receiving
doi_str_mv 10.1016/j.ijrobp.2012.09.028
format Article
fullrecord <record><control><sourceid>proquest_osti_</sourceid><recordid>TN_cdi_osti_scitechconnect_22224433</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S036030161203636X</els_id><sourcerecordid>1319184248</sourcerecordid><originalsourceid>FETCH-LOGICAL-c411t-b1593b0d56eaeb777d7cd6e9f415c52c1c706c7e8017e878c3eeec8d0bc117873</originalsourceid><addsrcrecordid>eNqFkc-O0zAQxi0EYsvCGyAUiQuXBE_sxAkHpKX8lSqQ2CLtzUomU-GQxl07rdQbb8grMVEWDlzwwR7Zv5n5_I0QT0FmIKF82WeuD749ZLmEPJN1JvPqnlhBZepUFcXNfbGSqpSpYvhCPIqxl1ICGP1QXOQKCi1NuRJG__qZfPZjuvaHoRmbkGzciUJy_ebr9lVyxU8nGpK3NMy352RL-H10t0d6LB7smiHSk7vzUnx7_267_phuvnz4tL7apKgBprSFolat7IqSGmqNMZ3BrqR6p6HAIkdAI0s0VEngzVSoiAirTrbIUiujLsXzpa6Pk7MR3cQK0I8j4WRzXlorxdSLhToEz-LiZPcuIg38I_LHaEFBDZXOdcWoXlAMPsZAO3sIbt-EswVpZ2Ntbxdj7WyslbVlYznt2V2HY7un7m_SHycZeL0AxG6cHIVZLI1InQuz1s67_3X4twAObnTYDD_oTLH3xzCy0xZs5Bx7PQ93ni3kHKnyRv0GYxCd6g</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1319184248</pqid></control><display><type>article</type><title>4π Non-Coplanar Liver SBRT: A Novel Delivery Technique</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Dong, Peng, PhD ; Lee, Percy, MD ; Ruan, Dan, PhD ; Long, Troy, BS ; Romeijn, Edwin, PhD ; Yang, Yingli, PhD ; Low, Daniel, PhD ; Kupelian, Patrick, MD ; Sheng, Ke, PhD</creator><creatorcontrib>Dong, Peng, PhD ; Lee, Percy, MD ; Ruan, Dan, PhD ; Long, Troy, BS ; Romeijn, Edwin, PhD ; Yang, Yingli, PhD ; Low, Daniel, PhD ; Kupelian, Patrick, MD ; Sheng, Ke, PhD</creatorcontrib><description>Purpose To improve the quality of liver stereotactic body radiation therapy (SBRT) treatments, a novel 4π framework was developed with accompanying algorithms to optimize non-coplanar beam orientations and fluences. The dose optimization is performed on a patient-specific deliverable beam geometry solution space, parameterized with patient and linear accelerator gantry orientations. Methods and Materials Beams causing collision between the gantry and the couch or patient were eliminated by simulating all beam orientations using a precise computer assisted design model of the linear accelerator and a human subject. Integrated beam orientation and fluence map optimizations were performed on remaining beams using a greedy column generation method. Testing of the new method was performed on 10 liver SBRT cases previously treated with 50 to 60 Gy in 5 fractions using volumetric modulated arc therapy (VMAT). For each patient, both 14 and 22 non-coplanar fields were selected and optimized to meet the objective of ≥95% of the planning target volume (PTV) covered by 100% of the prescription dose. Doses to organs at risk, normal liver volumes receiving &lt;15 Gy, integral dose, and 50% dose spillage volumes were compared against the delivered clinical VMAT plans. Results Compared with the VMAT plans, the 4π plans yielded reduced 50% dose spillage volume and integral dose by 22% (range 10%-40%) and 19% (range 13%-26%), respectively. The mean normal liver volume receiving &lt; 15 Gy was increased by 51 cc (range 21-107 cc) with a 31% reduction of the mean normal liver dose. Mean doses to the left kidney and right kidney and maximum doses to the stomach and spinal cord were on average reduced by 70%, 51%, 67%, and 64% ( P ≤.05). Conclusions This novel 4π non-coplanar radiation delivery technique significantly improved dose gradient, reduced high dose spillage, and improved organ at risk sparing compared with state of the art VMAT plans.</description><identifier>ISSN: 0360-3016</identifier><identifier>EISSN: 1879-355X</identifier><identifier>DOI: 10.1016/j.ijrobp.2012.09.028</identifier><identifier>PMID: 23154076</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>ALGORITHMS ; HEALTH HAZARDS ; Hematology, Oncology and Palliative Medicine ; Humans ; INTEGRAL DOSES ; Kidney - radiation effects ; KIDNEYS ; LINEAR ACCELERATORS ; LIVER ; Liver - diagnostic imaging ; Liver - radiation effects ; Liver Neoplasms - diagnostic imaging ; Liver Neoplasms - surgery ; OPTIMIZATION ; Organ Sparing Treatments - methods ; Organs at Risk - diagnostic imaging ; Organs at Risk - radiation effects ; Particle Accelerators - instrumentation ; PATIENTS ; Quality Improvement ; Radiation Injuries - prevention &amp; control ; Radiography ; Radiology ; RADIOLOGY AND NUCLEAR MEDICINE ; Radiosurgery - methods ; Radiosurgery - standards ; RADIOTHERAPY ; Radiotherapy Dosage - standards ; Radiotherapy Planning, Computer-Assisted - methods ; Radiotherapy, Intensity-Modulated - methods ; SPINAL CORD ; Spinal Cord - radiation effects ; STOMACH ; Stomach - radiation effects</subject><ispartof>International journal of radiation oncology, biology, physics, 2013-04, Vol.85 (5), p.1360-1366</ispartof><rights>Elsevier Inc.</rights><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c411t-b1593b0d56eaeb777d7cd6e9f415c52c1c706c7e8017e878c3eeec8d0bc117873</citedby><cites>FETCH-LOGICAL-c411t-b1593b0d56eaeb777d7cd6e9f415c52c1c706c7e8017e878c3eeec8d0bc117873</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S036030161203636X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23154076$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22224433$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Dong, Peng, PhD</creatorcontrib><creatorcontrib>Lee, Percy, MD</creatorcontrib><creatorcontrib>Ruan, Dan, PhD</creatorcontrib><creatorcontrib>Long, Troy, BS</creatorcontrib><creatorcontrib>Romeijn, Edwin, PhD</creatorcontrib><creatorcontrib>Yang, Yingli, PhD</creatorcontrib><creatorcontrib>Low, Daniel, PhD</creatorcontrib><creatorcontrib>Kupelian, Patrick, MD</creatorcontrib><creatorcontrib>Sheng, Ke, PhD</creatorcontrib><title>4π Non-Coplanar Liver SBRT: A Novel Delivery Technique</title><title>International journal of radiation oncology, biology, physics</title><addtitle>Int J Radiat Oncol Biol Phys</addtitle><description>Purpose To improve the quality of liver stereotactic body radiation therapy (SBRT) treatments, a novel 4π framework was developed with accompanying algorithms to optimize non-coplanar beam orientations and fluences. The dose optimization is performed on a patient-specific deliverable beam geometry solution space, parameterized with patient and linear accelerator gantry orientations. Methods and Materials Beams causing collision between the gantry and the couch or patient were eliminated by simulating all beam orientations using a precise computer assisted design model of the linear accelerator and a human subject. Integrated beam orientation and fluence map optimizations were performed on remaining beams using a greedy column generation method. Testing of the new method was performed on 10 liver SBRT cases previously treated with 50 to 60 Gy in 5 fractions using volumetric modulated arc therapy (VMAT). For each patient, both 14 and 22 non-coplanar fields were selected and optimized to meet the objective of ≥95% of the planning target volume (PTV) covered by 100% of the prescription dose. Doses to organs at risk, normal liver volumes receiving &lt;15 Gy, integral dose, and 50% dose spillage volumes were compared against the delivered clinical VMAT plans. Results Compared with the VMAT plans, the 4π plans yielded reduced 50% dose spillage volume and integral dose by 22% (range 10%-40%) and 19% (range 13%-26%), respectively. The mean normal liver volume receiving &lt; 15 Gy was increased by 51 cc (range 21-107 cc) with a 31% reduction of the mean normal liver dose. Mean doses to the left kidney and right kidney and maximum doses to the stomach and spinal cord were on average reduced by 70%, 51%, 67%, and 64% ( P ≤.05). Conclusions This novel 4π non-coplanar radiation delivery technique significantly improved dose gradient, reduced high dose spillage, and improved organ at risk sparing compared with state of the art VMAT plans.</description><subject>ALGORITHMS</subject><subject>HEALTH HAZARDS</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>INTEGRAL DOSES</subject><subject>Kidney - radiation effects</subject><subject>KIDNEYS</subject><subject>LINEAR ACCELERATORS</subject><subject>LIVER</subject><subject>Liver - diagnostic imaging</subject><subject>Liver - radiation effects</subject><subject>Liver Neoplasms - diagnostic imaging</subject><subject>Liver Neoplasms - surgery</subject><subject>OPTIMIZATION</subject><subject>Organ Sparing Treatments - methods</subject><subject>Organs at Risk - diagnostic imaging</subject><subject>Organs at Risk - radiation effects</subject><subject>Particle Accelerators - instrumentation</subject><subject>PATIENTS</subject><subject>Quality Improvement</subject><subject>Radiation Injuries - prevention &amp; control</subject><subject>Radiography</subject><subject>Radiology</subject><subject>RADIOLOGY AND NUCLEAR MEDICINE</subject><subject>Radiosurgery - methods</subject><subject>Radiosurgery - standards</subject><subject>RADIOTHERAPY</subject><subject>Radiotherapy Dosage - standards</subject><subject>Radiotherapy Planning, Computer-Assisted - methods</subject><subject>Radiotherapy, Intensity-Modulated - methods</subject><subject>SPINAL CORD</subject><subject>Spinal Cord - radiation effects</subject><subject>STOMACH</subject><subject>Stomach - radiation effects</subject><issn>0360-3016</issn><issn>1879-355X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc-O0zAQxi0EYsvCGyAUiQuXBE_sxAkHpKX8lSqQ2CLtzUomU-GQxl07rdQbb8grMVEWDlzwwR7Zv5n5_I0QT0FmIKF82WeuD749ZLmEPJN1JvPqnlhBZepUFcXNfbGSqpSpYvhCPIqxl1ICGP1QXOQKCi1NuRJG__qZfPZjuvaHoRmbkGzciUJy_ebr9lVyxU8nGpK3NMy352RL-H10t0d6LB7smiHSk7vzUnx7_267_phuvnz4tL7apKgBprSFolat7IqSGmqNMZ3BrqR6p6HAIkdAI0s0VEngzVSoiAirTrbIUiujLsXzpa6Pk7MR3cQK0I8j4WRzXlorxdSLhToEz-LiZPcuIg38I_LHaEFBDZXOdcWoXlAMPsZAO3sIbt-EswVpZ2Ntbxdj7WyslbVlYznt2V2HY7un7m_SHycZeL0AxG6cHIVZLI1InQuz1s67_3X4twAObnTYDD_oTLH3xzCy0xZs5Bx7PQ93ni3kHKnyRv0GYxCd6g</recordid><startdate>20130401</startdate><enddate>20130401</enddate><creator>Dong, Peng, PhD</creator><creator>Lee, Percy, MD</creator><creator>Ruan, Dan, PhD</creator><creator>Long, Troy, BS</creator><creator>Romeijn, Edwin, PhD</creator><creator>Yang, Yingli, PhD</creator><creator>Low, Daniel, PhD</creator><creator>Kupelian, Patrick, MD</creator><creator>Sheng, Ke, PhD</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>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>20130401</creationdate><title>4π Non-Coplanar Liver SBRT: A Novel Delivery Technique</title><author>Dong, Peng, PhD ; Lee, Percy, MD ; Ruan, Dan, PhD ; Long, Troy, BS ; Romeijn, Edwin, PhD ; Yang, Yingli, PhD ; Low, Daniel, PhD ; Kupelian, Patrick, MD ; Sheng, Ke, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c411t-b1593b0d56eaeb777d7cd6e9f415c52c1c706c7e8017e878c3eeec8d0bc117873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>ALGORITHMS</topic><topic>HEALTH HAZARDS</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>INTEGRAL DOSES</topic><topic>Kidney - radiation effects</topic><topic>KIDNEYS</topic><topic>LINEAR ACCELERATORS</topic><topic>LIVER</topic><topic>Liver - diagnostic imaging</topic><topic>Liver - radiation effects</topic><topic>Liver Neoplasms - diagnostic imaging</topic><topic>Liver Neoplasms - surgery</topic><topic>OPTIMIZATION</topic><topic>Organ Sparing Treatments - methods</topic><topic>Organs at Risk - diagnostic imaging</topic><topic>Organs at Risk - radiation effects</topic><topic>Particle Accelerators - instrumentation</topic><topic>PATIENTS</topic><topic>Quality Improvement</topic><topic>Radiation Injuries - prevention &amp; control</topic><topic>Radiography</topic><topic>Radiology</topic><topic>RADIOLOGY AND NUCLEAR MEDICINE</topic><topic>Radiosurgery - methods</topic><topic>Radiosurgery - standards</topic><topic>RADIOTHERAPY</topic><topic>Radiotherapy Dosage - standards</topic><topic>Radiotherapy Planning, Computer-Assisted - methods</topic><topic>Radiotherapy, Intensity-Modulated - methods</topic><topic>SPINAL CORD</topic><topic>Spinal Cord - radiation effects</topic><topic>STOMACH</topic><topic>Stomach - radiation effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dong, Peng, PhD</creatorcontrib><creatorcontrib>Lee, Percy, MD</creatorcontrib><creatorcontrib>Ruan, Dan, PhD</creatorcontrib><creatorcontrib>Long, Troy, BS</creatorcontrib><creatorcontrib>Romeijn, Edwin, PhD</creatorcontrib><creatorcontrib>Yang, Yingli, PhD</creatorcontrib><creatorcontrib>Low, Daniel, PhD</creatorcontrib><creatorcontrib>Kupelian, Patrick, MD</creatorcontrib><creatorcontrib>Sheng, Ke, PhD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</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>Dong, Peng, PhD</au><au>Lee, Percy, MD</au><au>Ruan, Dan, PhD</au><au>Long, Troy, BS</au><au>Romeijn, Edwin, PhD</au><au>Yang, Yingli, PhD</au><au>Low, Daniel, PhD</au><au>Kupelian, Patrick, MD</au><au>Sheng, Ke, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>4π Non-Coplanar Liver SBRT: A Novel Delivery Technique</atitle><jtitle>International journal of radiation oncology, biology, physics</jtitle><addtitle>Int J Radiat Oncol Biol Phys</addtitle><date>2013-04-01</date><risdate>2013</risdate><volume>85</volume><issue>5</issue><spage>1360</spage><epage>1366</epage><pages>1360-1366</pages><issn>0360-3016</issn><eissn>1879-355X</eissn><abstract>Purpose To improve the quality of liver stereotactic body radiation therapy (SBRT) treatments, a novel 4π framework was developed with accompanying algorithms to optimize non-coplanar beam orientations and fluences. The dose optimization is performed on a patient-specific deliverable beam geometry solution space, parameterized with patient and linear accelerator gantry orientations. Methods and Materials Beams causing collision between the gantry and the couch or patient were eliminated by simulating all beam orientations using a precise computer assisted design model of the linear accelerator and a human subject. Integrated beam orientation and fluence map optimizations were performed on remaining beams using a greedy column generation method. Testing of the new method was performed on 10 liver SBRT cases previously treated with 50 to 60 Gy in 5 fractions using volumetric modulated arc therapy (VMAT). For each patient, both 14 and 22 non-coplanar fields were selected and optimized to meet the objective of ≥95% of the planning target volume (PTV) covered by 100% of the prescription dose. Doses to organs at risk, normal liver volumes receiving &lt;15 Gy, integral dose, and 50% dose spillage volumes were compared against the delivered clinical VMAT plans. Results Compared with the VMAT plans, the 4π plans yielded reduced 50% dose spillage volume and integral dose by 22% (range 10%-40%) and 19% (range 13%-26%), respectively. The mean normal liver volume receiving &lt; 15 Gy was increased by 51 cc (range 21-107 cc) with a 31% reduction of the mean normal liver dose. Mean doses to the left kidney and right kidney and maximum doses to the stomach and spinal cord were on average reduced by 70%, 51%, 67%, and 64% ( P ≤.05). Conclusions This novel 4π non-coplanar radiation delivery technique significantly improved dose gradient, reduced high dose spillage, and improved organ at risk sparing compared with state of the art VMAT plans.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>23154076</pmid><doi>10.1016/j.ijrobp.2012.09.028</doi><tpages>7</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0360-3016
ispartof International journal of radiation oncology, biology, physics, 2013-04, Vol.85 (5), p.1360-1366
issn 0360-3016
1879-355X
language eng
recordid cdi_osti_scitechconnect_22224433
source MEDLINE; Elsevier ScienceDirect Journals Complete
subjects ALGORITHMS
HEALTH HAZARDS
Hematology, Oncology and Palliative Medicine
Humans
INTEGRAL DOSES
Kidney - radiation effects
KIDNEYS
LINEAR ACCELERATORS
LIVER
Liver - diagnostic imaging
Liver - radiation effects
Liver Neoplasms - diagnostic imaging
Liver Neoplasms - surgery
OPTIMIZATION
Organ Sparing Treatments - methods
Organs at Risk - diagnostic imaging
Organs at Risk - radiation effects
Particle Accelerators - instrumentation
PATIENTS
Quality Improvement
Radiation Injuries - prevention & control
Radiography
Radiology
RADIOLOGY AND NUCLEAR MEDICINE
Radiosurgery - methods
Radiosurgery - standards
RADIOTHERAPY
Radiotherapy Dosage - standards
Radiotherapy Planning, Computer-Assisted - methods
Radiotherapy, Intensity-Modulated - methods
SPINAL CORD
Spinal Cord - radiation effects
STOMACH
Stomach - radiation effects
title 4π Non-Coplanar Liver SBRT: A Novel Delivery Technique
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T21%3A46%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_osti_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=4%CF%80%20Non-Coplanar%20Liver%20SBRT:%20A%20Novel%20Delivery%20Technique&rft.jtitle=International%20journal%20of%20radiation%20oncology,%20biology,%20physics&rft.au=Dong,%20Peng,%20PhD&rft.date=2013-04-01&rft.volume=85&rft.issue=5&rft.spage=1360&rft.epage=1366&rft.pages=1360-1366&rft.issn=0360-3016&rft.eissn=1879-355X&rft_id=info:doi/10.1016/j.ijrobp.2012.09.028&rft_dat=%3Cproquest_osti_%3E1319184248%3C/proquest_osti_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1319184248&rft_id=info:pmid/23154076&rft_els_id=1_s2_0_S036030161203636X&rfr_iscdi=true