Effect of Time, Dose, and Fractionation on Temporal Lobe Necrosis Following Radiotherapy for Nasopharyngeal Carcinoma
Purpose: To study the relative effects of different radiation factors on temporal lobe necrosis (TLN) and predictive accuracy of different biological equivalent models. Methods and Materials: Consecutive patients (1008) treated radically with four different fractionation schedules during 1976–1985 f...
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| Veröffentlicht in: | International journal of radiation oncology, biology, physics biology, physics, 1998, Vol.40 (1), p.35-42 |
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| creator | Lee, Anne W.M. Foo, William Chappell, Rick Fowler, Jack F. Sze, W.M. Poon, Y.F. Law, Stephen C.K. Ng, S.H. O, S.K. Tung, Stewart Y. Lau, W.H. Ho, John H.C. |
| description | Purpose: To study the relative effects of different radiation factors on temporal lobe necrosis (TLN) and predictive accuracy of different biological equivalent models.
Methods and Materials: Consecutive patients (1008) treated radically with four different fractionation schedules during 1976–1985 for T1 nasopharyngeal carcinoma were retrospectively analyzed. All were irradiated by megavoltage photons using the same technique. Their age ranged from 18–84 years, and 92% of patients had complete follow-up. The fractional dose to inferomedial parts of both temporal lobes ranged from 2.5–4.2 Gy, total dose 45.6–60 Gy, and overall time 38–75 days.
Results: Despite a lower total dose of 50.4 Gy, the 621 patients irradiated with 4.2 Gy per fraction had a significantly higher incidence of temporal lobe necrosis than the 320 patients treated to 60 Gy with 2.5 Gy per fraction: the 10-year actuarial incidence being 18.6% vs. 4.6%,
p
< 0.001. Multivariate survival analysis showed that fractional effect (product of total dose and fractional dose) was the most significant factor:
p
= 0.0022, hazard ratio (HR) = 1.044 per Gy
2. Overall time and age were both insignificant. The α/β ratio calculated from our data was 2.9 Gy (95% CI: −1.8, 7.6 Gy). Biological effective dose (BED
Gy3), neuret, and brain tolerance unit all showed strongly significant correlation with the necrotic rate (
p
< 0.001), and gave similar predictions. The hazard of TLN increased by 14% per Gy
3, and it was estimated that 64 Gy (at conventional fractionation of 2 Gy daily) would lead to a 5% necrotic rate at 10 years. Not only did the nominal standard dose (NSD) show the lowest value in terms of log likelihood and standardized HR, but its predictions on TLN deviated markedly from clinically observed rates.
Conclusion: Fractional effect is the most significant factor affecting cerebral necrosis, and overall time has little protective effect. The BED formula, assuming an α/β ratio of 3 Gy, is an appropriate model for predicting late effects on the temporal lobe, and NSD could give seriously misleading predictions. |
| doi_str_mv | 10.1016/S0360-3016(97)00580-4 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_16212256</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0360301697005804</els_id><sourcerecordid>16212256</sourcerecordid><originalsourceid>FETCH-LOGICAL-c585t-efdf69334467e053160f273995113084e18af8848774490fdb41fe94aa0fa043</originalsourceid><addsrcrecordid>eNqFkVFr2zAQgEXpaLN2P6Ggh1E2mFfJkmzrqYys2Qahgy0PexMX-dRq2JYrORv995ObkNeBOAnuO93pEyFXnH3kjFc3P5moWCHy8Z2u3zOmGlbIE7LgTa0LodSvU7I4IufkdUq_GWOc1_KMnGlZlkqpBdndOYd2osHRje_xA_0cUo4wtHQVwU4-DDAHmtcG-zFE6Og6bJHeo40h-URXoevCXz880B_Q-jA9YoTxmboQ6T2kMD5CfB4eMNctIVo_hB4uySsHXcI3h_2CbFZ3m-XXYv39y7flp3VhVaOmAl3rKi2ElFWNTAleMVfWQmvFuWCNRN6AaxrZ1LWUmrl2K7lDLQGYAybFBbneXzvG8LTDNJneJ4tdBwOGXTK8Knn2UGVQ7cH5SSmiM2P0fZ7bcGZm2-bFtplVGl2bF9tmbnB1aLDb9tgeqw56c_7tIQ_JQuciDNanI1ZywWWpM3a7xzC7-OMxmmQ9DhZbH_PnmDb4_wzyD5iwm1I</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>16212256</pqid></control><display><type>article</type><title>Effect of Time, Dose, and Fractionation on Temporal Lobe Necrosis Following Radiotherapy for Nasopharyngeal Carcinoma</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Lee, Anne W.M. ; Foo, William ; Chappell, Rick ; Fowler, Jack F. ; Sze, W.M. ; Poon, Y.F. ; Law, Stephen C.K. ; Ng, S.H. ; O, S.K. ; Tung, Stewart Y. ; Lau, W.H. ; Ho, John H.C.</creator><creatorcontrib>Lee, Anne W.M. ; Foo, William ; Chappell, Rick ; Fowler, Jack F. ; Sze, W.M. ; Poon, Y.F. ; Law, Stephen C.K. ; Ng, S.H. ; O, S.K. ; Tung, Stewart Y. ; Lau, W.H. ; Ho, John H.C.</creatorcontrib><description>Purpose: To study the relative effects of different radiation factors on temporal lobe necrosis (TLN) and predictive accuracy of different biological equivalent models.
Methods and Materials: Consecutive patients (1008) treated radically with four different fractionation schedules during 1976–1985 for T1 nasopharyngeal carcinoma were retrospectively analyzed. All were irradiated by megavoltage photons using the same technique. Their age ranged from 18–84 years, and 92% of patients had complete follow-up. The fractional dose to inferomedial parts of both temporal lobes ranged from 2.5–4.2 Gy, total dose 45.6–60 Gy, and overall time 38–75 days.
Results: Despite a lower total dose of 50.4 Gy, the 621 patients irradiated with 4.2 Gy per fraction had a significantly higher incidence of temporal lobe necrosis than the 320 patients treated to 60 Gy with 2.5 Gy per fraction: the 10-year actuarial incidence being 18.6% vs. 4.6%,
p
< 0.001. Multivariate survival analysis showed that fractional effect (product of total dose and fractional dose) was the most significant factor:
p
= 0.0022, hazard ratio (HR) = 1.044 per Gy
2. Overall time and age were both insignificant. The α/β ratio calculated from our data was 2.9 Gy (95% CI: −1.8, 7.6 Gy). Biological effective dose (BED
Gy3), neuret, and brain tolerance unit all showed strongly significant correlation with the necrotic rate (
p
< 0.001), and gave similar predictions. The hazard of TLN increased by 14% per Gy
3, and it was estimated that 64 Gy (at conventional fractionation of 2 Gy daily) would lead to a 5% necrotic rate at 10 years. Not only did the nominal standard dose (NSD) show the lowest value in terms of log likelihood and standardized HR, but its predictions on TLN deviated markedly from clinically observed rates.
Conclusion: Fractional effect is the most significant factor affecting cerebral necrosis, and overall time has little protective effect. The BED formula, assuming an α/β ratio of 3 Gy, is an appropriate model for predicting late effects on the temporal lobe, and NSD could give seriously misleading predictions.</description><identifier>ISSN: 0360-3016</identifier><identifier>EISSN: 1879-355X</identifier><identifier>DOI: 10.1016/S0360-3016(97)00580-4</identifier><identifier>PMID: 9422555</identifier><identifier>CODEN: IOBPD3</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Biological equivalent formulas ; Brain Diseases - etiology ; Carcinoma, Squamous Cell - radiotherapy ; Cerebral necrosis ; Dose ; Dose Fractionation, Radiation ; Female ; Fractionation ; Humans ; Male ; Medical sciences ; Middle Aged ; Nasopharyngeal carcinoma ; Nasopharyngeal Neoplasms - radiotherapy ; Necrosis ; Otorhinolaryngology (head neck, general aspects and miscellaneous) ; Otorhinolaryngology. Stomatology ; Prediction of necrotic rates ; Radiation Injuries - etiology ; Radiation Injuries - pathology ; Radiobiology ; Temporal Lobe - pathology ; Temporal Lobe - radiation effects ; Time ; Time Factors ; Tumors</subject><ispartof>International journal of radiation oncology, biology, physics, 1998, Vol.40 (1), p.35-42</ispartof><rights>1998 Elsevier Science Inc.</rights><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c585t-efdf69334467e053160f273995113084e18af8848774490fdb41fe94aa0fa043</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0360301697005804$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,4010,27900,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2131429$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9422555$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Anne W.M.</creatorcontrib><creatorcontrib>Foo, William</creatorcontrib><creatorcontrib>Chappell, Rick</creatorcontrib><creatorcontrib>Fowler, Jack F.</creatorcontrib><creatorcontrib>Sze, W.M.</creatorcontrib><creatorcontrib>Poon, Y.F.</creatorcontrib><creatorcontrib>Law, Stephen C.K.</creatorcontrib><creatorcontrib>Ng, S.H.</creatorcontrib><creatorcontrib>O, S.K.</creatorcontrib><creatorcontrib>Tung, Stewart Y.</creatorcontrib><creatorcontrib>Lau, W.H.</creatorcontrib><creatorcontrib>Ho, John H.C.</creatorcontrib><title>Effect of Time, Dose, and Fractionation on Temporal Lobe Necrosis Following Radiotherapy for Nasopharyngeal Carcinoma</title><title>International journal of radiation oncology, biology, physics</title><addtitle>Int J Radiat Oncol Biol Phys</addtitle><description>Purpose: To study the relative effects of different radiation factors on temporal lobe necrosis (TLN) and predictive accuracy of different biological equivalent models.
Methods and Materials: Consecutive patients (1008) treated radically with four different fractionation schedules during 1976–1985 for T1 nasopharyngeal carcinoma were retrospectively analyzed. All were irradiated by megavoltage photons using the same technique. Their age ranged from 18–84 years, and 92% of patients had complete follow-up. The fractional dose to inferomedial parts of both temporal lobes ranged from 2.5–4.2 Gy, total dose 45.6–60 Gy, and overall time 38–75 days.
Results: Despite a lower total dose of 50.4 Gy, the 621 patients irradiated with 4.2 Gy per fraction had a significantly higher incidence of temporal lobe necrosis than the 320 patients treated to 60 Gy with 2.5 Gy per fraction: the 10-year actuarial incidence being 18.6% vs. 4.6%,
p
< 0.001. Multivariate survival analysis showed that fractional effect (product of total dose and fractional dose) was the most significant factor:
p
= 0.0022, hazard ratio (HR) = 1.044 per Gy
2. Overall time and age were both insignificant. The α/β ratio calculated from our data was 2.9 Gy (95% CI: −1.8, 7.6 Gy). Biological effective dose (BED
Gy3), neuret, and brain tolerance unit all showed strongly significant correlation with the necrotic rate (
p
< 0.001), and gave similar predictions. The hazard of TLN increased by 14% per Gy
3, and it was estimated that 64 Gy (at conventional fractionation of 2 Gy daily) would lead to a 5% necrotic rate at 10 years. Not only did the nominal standard dose (NSD) show the lowest value in terms of log likelihood and standardized HR, but its predictions on TLN deviated markedly from clinically observed rates.
Conclusion: Fractional effect is the most significant factor affecting cerebral necrosis, and overall time has little protective effect. The BED formula, assuming an α/β ratio of 3 Gy, is an appropriate model for predicting late effects on the temporal lobe, and NSD could give seriously misleading predictions.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Biological equivalent formulas</subject><subject>Brain Diseases - etiology</subject><subject>Carcinoma, Squamous Cell - radiotherapy</subject><subject>Cerebral necrosis</subject><subject>Dose</subject><subject>Dose Fractionation, Radiation</subject><subject>Female</subject><subject>Fractionation</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Nasopharyngeal carcinoma</subject><subject>Nasopharyngeal Neoplasms - radiotherapy</subject><subject>Necrosis</subject><subject>Otorhinolaryngology (head neck, general aspects and miscellaneous)</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Prediction of necrotic rates</subject><subject>Radiation Injuries - etiology</subject><subject>Radiation Injuries - pathology</subject><subject>Radiobiology</subject><subject>Temporal Lobe - pathology</subject><subject>Temporal Lobe - radiation effects</subject><subject>Time</subject><subject>Time Factors</subject><subject>Tumors</subject><issn>0360-3016</issn><issn>1879-355X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkVFr2zAQgEXpaLN2P6Ggh1E2mFfJkmzrqYys2Qahgy0PexMX-dRq2JYrORv995ObkNeBOAnuO93pEyFXnH3kjFc3P5moWCHy8Z2u3zOmGlbIE7LgTa0LodSvU7I4IufkdUq_GWOc1_KMnGlZlkqpBdndOYd2osHRje_xA_0cUo4wtHQVwU4-DDAHmtcG-zFE6Og6bJHeo40h-URXoevCXz880B_Q-jA9YoTxmboQ6T2kMD5CfB4eMNctIVo_hB4uySsHXcI3h_2CbFZ3m-XXYv39y7flp3VhVaOmAl3rKi2ElFWNTAleMVfWQmvFuWCNRN6AaxrZ1LWUmrl2K7lDLQGYAybFBbneXzvG8LTDNJneJ4tdBwOGXTK8Knn2UGVQ7cH5SSmiM2P0fZ7bcGZm2-bFtplVGl2bF9tmbnB1aLDb9tgeqw56c_7tIQ_JQuciDNanI1ZywWWpM3a7xzC7-OMxmmQ9DhZbH_PnmDb4_wzyD5iwm1I</recordid><startdate>1998</startdate><enddate>1998</enddate><creator>Lee, Anne W.M.</creator><creator>Foo, William</creator><creator>Chappell, Rick</creator><creator>Fowler, Jack F.</creator><creator>Sze, W.M.</creator><creator>Poon, Y.F.</creator><creator>Law, Stephen C.K.</creator><creator>Ng, S.H.</creator><creator>O, S.K.</creator><creator>Tung, Stewart Y.</creator><creator>Lau, W.H.</creator><creator>Ho, John H.C.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><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>7U7</scope><scope>C1K</scope></search><sort><creationdate>1998</creationdate><title>Effect of Time, Dose, and Fractionation on Temporal Lobe Necrosis Following Radiotherapy for Nasopharyngeal Carcinoma</title><author>Lee, Anne W.M. ; Foo, William ; Chappell, Rick ; Fowler, Jack F. ; Sze, W.M. ; Poon, Y.F. ; Law, Stephen C.K. ; Ng, S.H. ; O, S.K. ; Tung, Stewart Y. ; Lau, W.H. ; Ho, John H.C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c585t-efdf69334467e053160f273995113084e18af8848774490fdb41fe94aa0fa043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological and medical sciences</topic><topic>Biological equivalent formulas</topic><topic>Brain Diseases - etiology</topic><topic>Carcinoma, Squamous Cell - radiotherapy</topic><topic>Cerebral necrosis</topic><topic>Dose</topic><topic>Dose Fractionation, Radiation</topic><topic>Female</topic><topic>Fractionation</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Nasopharyngeal carcinoma</topic><topic>Nasopharyngeal Neoplasms - radiotherapy</topic><topic>Necrosis</topic><topic>Otorhinolaryngology (head neck, general aspects and miscellaneous)</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>Prediction of necrotic rates</topic><topic>Radiation Injuries - etiology</topic><topic>Radiation Injuries - pathology</topic><topic>Radiobiology</topic><topic>Temporal Lobe - pathology</topic><topic>Temporal Lobe - radiation effects</topic><topic>Time</topic><topic>Time Factors</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Anne W.M.</creatorcontrib><creatorcontrib>Foo, William</creatorcontrib><creatorcontrib>Chappell, Rick</creatorcontrib><creatorcontrib>Fowler, Jack F.</creatorcontrib><creatorcontrib>Sze, W.M.</creatorcontrib><creatorcontrib>Poon, Y.F.</creatorcontrib><creatorcontrib>Law, Stephen C.K.</creatorcontrib><creatorcontrib>Ng, S.H.</creatorcontrib><creatorcontrib>O, S.K.</creatorcontrib><creatorcontrib>Tung, Stewart Y.</creatorcontrib><creatorcontrib>Lau, W.H.</creatorcontrib><creatorcontrib>Ho, John H.C.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>International journal of radiation oncology, biology, physics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Anne W.M.</au><au>Foo, William</au><au>Chappell, Rick</au><au>Fowler, Jack F.</au><au>Sze, W.M.</au><au>Poon, Y.F.</au><au>Law, Stephen C.K.</au><au>Ng, S.H.</au><au>O, S.K.</au><au>Tung, Stewart Y.</au><au>Lau, W.H.</au><au>Ho, John H.C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of Time, Dose, and Fractionation on Temporal Lobe Necrosis Following Radiotherapy for Nasopharyngeal Carcinoma</atitle><jtitle>International journal of radiation oncology, biology, physics</jtitle><addtitle>Int J Radiat Oncol Biol Phys</addtitle><date>1998</date><risdate>1998</risdate><volume>40</volume><issue>1</issue><spage>35</spage><epage>42</epage><pages>35-42</pages><issn>0360-3016</issn><eissn>1879-355X</eissn><coden>IOBPD3</coden><abstract>Purpose: To study the relative effects of different radiation factors on temporal lobe necrosis (TLN) and predictive accuracy of different biological equivalent models.
Methods and Materials: Consecutive patients (1008) treated radically with four different fractionation schedules during 1976–1985 for T1 nasopharyngeal carcinoma were retrospectively analyzed. All were irradiated by megavoltage photons using the same technique. Their age ranged from 18–84 years, and 92% of patients had complete follow-up. The fractional dose to inferomedial parts of both temporal lobes ranged from 2.5–4.2 Gy, total dose 45.6–60 Gy, and overall time 38–75 days.
Results: Despite a lower total dose of 50.4 Gy, the 621 patients irradiated with 4.2 Gy per fraction had a significantly higher incidence of temporal lobe necrosis than the 320 patients treated to 60 Gy with 2.5 Gy per fraction: the 10-year actuarial incidence being 18.6% vs. 4.6%,
p
< 0.001. Multivariate survival analysis showed that fractional effect (product of total dose and fractional dose) was the most significant factor:
p
= 0.0022, hazard ratio (HR) = 1.044 per Gy
2. Overall time and age were both insignificant. The α/β ratio calculated from our data was 2.9 Gy (95% CI: −1.8, 7.6 Gy). Biological effective dose (BED
Gy3), neuret, and brain tolerance unit all showed strongly significant correlation with the necrotic rate (
p
< 0.001), and gave similar predictions. The hazard of TLN increased by 14% per Gy
3, and it was estimated that 64 Gy (at conventional fractionation of 2 Gy daily) would lead to a 5% necrotic rate at 10 years. Not only did the nominal standard dose (NSD) show the lowest value in terms of log likelihood and standardized HR, but its predictions on TLN deviated markedly from clinically observed rates.
Conclusion: Fractional effect is the most significant factor affecting cerebral necrosis, and overall time has little protective effect. The BED formula, assuming an α/β ratio of 3 Gy, is an appropriate model for predicting late effects on the temporal lobe, and NSD could give seriously misleading predictions.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>9422555</pmid><doi>10.1016/S0360-3016(97)00580-4</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Aged Aged, 80 and over Biological and medical sciences Biological equivalent formulas Brain Diseases - etiology Carcinoma, Squamous Cell - radiotherapy Cerebral necrosis Dose Dose Fractionation, Radiation Female Fractionation Humans Male Medical sciences Middle Aged Nasopharyngeal carcinoma Nasopharyngeal Neoplasms - radiotherapy Necrosis Otorhinolaryngology (head neck, general aspects and miscellaneous) Otorhinolaryngology. Stomatology Prediction of necrotic rates Radiation Injuries - etiology Radiation Injuries - pathology Radiobiology Temporal Lobe - pathology Temporal Lobe - radiation effects Time Time Factors Tumors |
| title | Effect of Time, Dose, and Fractionation on Temporal Lobe Necrosis Following Radiotherapy for Nasopharyngeal Carcinoma |
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