Urethral and bladder dosimetry of total and focal salvage Iodine-125 prostate brachytherapy: Late toxicity and dose constraints

Abstract Introduction Salvage Iodine-125 brachytherapy (I-125-BT) constitutes a curative treatment approach for patients with organ-confined recurrent prostate cancer after primary radiotherapy. Currently, focal salvage (FS) instead of whole-gland or total salvage (TS) is being investigated, to redu...

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Veröffentlicht in:Radiotherapy and oncology 2015-11, Vol.117 (2), p.262-269
Hauptverfasser: Peters, Max, van der Voort van Zyp, Jochem, Hoekstra, Carel, Westendorp, Hendrik, van de Pol, Sandrine, Moerland, Marinus, Maenhout, Metha, Kattevilder, Rob, van Vulpen, Marco
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container_end_page 269
container_issue 2
container_start_page 262
container_title Radiotherapy and oncology
container_volume 117
creator Peters, Max
van der Voort van Zyp, Jochem
Hoekstra, Carel
Westendorp, Hendrik
van de Pol, Sandrine
Moerland, Marinus
Maenhout, Metha
Kattevilder, Rob
van Vulpen, Marco
description Abstract Introduction Salvage Iodine-125 brachytherapy (I-125-BT) constitutes a curative treatment approach for patients with organ-confined recurrent prostate cancer after primary radiotherapy. Currently, focal salvage (FS) instead of whole-gland or total salvage (TS) is being investigated, to reduce severe toxicity associated with cumulative radiation dose. Differences in urethral and bladder dosimetry and constraints to reduce late (>90 days) genitourinary (GU) toxicity are presented here. Materials and methods Dosimetry on intraoperative ultrasound (US) of 20 FS and 28 TS patients was compared. The prostate, bladder, urethra and bulbomembranous (BM) urethra were delineated. Toxicity was assessed using the CTCAE version 4.0. Dose constraints to reduce toxicity in TS patients were evaluated with receiver operating characteristic (ROC) analysis. Results FS I-125 BT significantly reduces bladder and urethral dose compared to TS. Grade 3 GU toxicity occurred once in the FS group. For TS patients late severe (⩾grade 3) GU toxicity was frequent (38% in the total 61 patients and 56% in the 27 analyzed patients). TS patients with ⩾grade 3 GU toxicity showed higher bladder D2 cc than TS patients without toxicity (median 43 Gy) ( p = 0.02). The urethral V100 was significantly higher in TS patients with several toxicity profiles: ⩾grade 3 urethral strictures, ⩾grade 2 urinary retention and multiple ⩾grade 2 GU toxicity events. Dose to the BM urethra did not show a relation with stricture formation. ROC-analysis indicated a bladder D2 cc
doi_str_mv 10.1016/j.radonc.2015.08.018
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Currently, focal salvage (FS) instead of whole-gland or total salvage (TS) is being investigated, to reduce severe toxicity associated with cumulative radiation dose. Differences in urethral and bladder dosimetry and constraints to reduce late (&gt;90 days) genitourinary (GU) toxicity are presented here. Materials and methods Dosimetry on intraoperative ultrasound (US) of 20 FS and 28 TS patients was compared. The prostate, bladder, urethra and bulbomembranous (BM) urethra were delineated. Toxicity was assessed using the CTCAE version 4.0. Dose constraints to reduce toxicity in TS patients were evaluated with receiver operating characteristic (ROC) analysis. Results FS I-125 BT significantly reduces bladder and urethral dose compared to TS. Grade 3 GU toxicity occurred once in the FS group. For TS patients late severe (⩾grade 3) GU toxicity was frequent (38% in the total 61 patients and 56% in the 27 analyzed patients). TS patients with ⩾grade 3 GU toxicity showed higher bladder D2 cc than TS patients without toxicity (median 43 Gy) ( p = 0.02). The urethral V100 was significantly higher in TS patients with several toxicity profiles: ⩾grade 3 urethral strictures, ⩾grade 2 urinary retention and multiple ⩾grade 2 GU toxicity events. Dose to the BM urethra did not show a relation with stricture formation. ROC-analysis indicated a bladder D2 cc &lt;70 Gy to prevent ⩾grade 3 GU toxicity (AUC 0.76, 95%CI: 0.56–0.96, p = 0.02). A urethral V100 &lt;0.40 cc (AUC from 0.73–0.91, p = 0.003–0.05) could prevent other late GU toxicity. Conclusion FS I-125 BT reduces urethral and bladder dose significantly compared to TS. With TS, there is an increased risk of cumulative dose and severe GU toxicity. Based on these findings, bladder D2 cc should be below 70 Gy and urethral V100 below 0.40 cc.</description><identifier>ISSN: 0167-8140</identifier><identifier>EISSN: 1879-0887</identifier><identifier>DOI: 10.1016/j.radonc.2015.08.018</identifier><identifier>PMID: 26349590</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Aged ; Brachytherapy - adverse effects ; Brachytherapy - methods ; Dosimetry ; Focal salvage ; GU toxicity ; Hematology, Oncology and Palliative Medicine ; Humans ; I125 brachytherapy ; Iodine Radioisotopes - therapeutic use ; Male ; Prostate cancer ; Prostatic Neoplasms - radiotherapy ; Radiation Injuries - prevention &amp; control ; Radiometry ; Radiotherapy Dosage ; Salvage Therapy - methods ; Total salvage ; Urethra - radiation effects ; Urinary Bladder - radiation effects</subject><ispartof>Radiotherapy and oncology, 2015-11, Vol.117 (2), p.262-269</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2015 Elsevier Ireland Ltd</rights><rights>Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c553t-6b74734b34ca97fd98eba7a54ea196ef0f6ff240bae67e2323399d64d4f329a23</citedby><cites>FETCH-LOGICAL-c553t-6b74734b34ca97fd98eba7a54ea196ef0f6ff240bae67e2323399d64d4f329a23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.radonc.2015.08.018$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26349590$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Peters, Max</creatorcontrib><creatorcontrib>van der Voort van Zyp, Jochem</creatorcontrib><creatorcontrib>Hoekstra, Carel</creatorcontrib><creatorcontrib>Westendorp, Hendrik</creatorcontrib><creatorcontrib>van de Pol, Sandrine</creatorcontrib><creatorcontrib>Moerland, Marinus</creatorcontrib><creatorcontrib>Maenhout, Metha</creatorcontrib><creatorcontrib>Kattevilder, Rob</creatorcontrib><creatorcontrib>van Vulpen, Marco</creatorcontrib><title>Urethral and bladder dosimetry of total and focal salvage Iodine-125 prostate brachytherapy: Late toxicity and dose constraints</title><title>Radiotherapy and oncology</title><addtitle>Radiother Oncol</addtitle><description>Abstract Introduction Salvage Iodine-125 brachytherapy (I-125-BT) constitutes a curative treatment approach for patients with organ-confined recurrent prostate cancer after primary radiotherapy. Currently, focal salvage (FS) instead of whole-gland or total salvage (TS) is being investigated, to reduce severe toxicity associated with cumulative radiation dose. Differences in urethral and bladder dosimetry and constraints to reduce late (&gt;90 days) genitourinary (GU) toxicity are presented here. Materials and methods Dosimetry on intraoperative ultrasound (US) of 20 FS and 28 TS patients was compared. The prostate, bladder, urethra and bulbomembranous (BM) urethra were delineated. Toxicity was assessed using the CTCAE version 4.0. Dose constraints to reduce toxicity in TS patients were evaluated with receiver operating characteristic (ROC) analysis. Results FS I-125 BT significantly reduces bladder and urethral dose compared to TS. Grade 3 GU toxicity occurred once in the FS group. For TS patients late severe (⩾grade 3) GU toxicity was frequent (38% in the total 61 patients and 56% in the 27 analyzed patients). TS patients with ⩾grade 3 GU toxicity showed higher bladder D2 cc than TS patients without toxicity (median 43 Gy) ( p = 0.02). The urethral V100 was significantly higher in TS patients with several toxicity profiles: ⩾grade 3 urethral strictures, ⩾grade 2 urinary retention and multiple ⩾grade 2 GU toxicity events. Dose to the BM urethra did not show a relation with stricture formation. ROC-analysis indicated a bladder D2 cc &lt;70 Gy to prevent ⩾grade 3 GU toxicity (AUC 0.76, 95%CI: 0.56–0.96, p = 0.02). A urethral V100 &lt;0.40 cc (AUC from 0.73–0.91, p = 0.003–0.05) could prevent other late GU toxicity. Conclusion FS I-125 BT reduces urethral and bladder dose significantly compared to TS. With TS, there is an increased risk of cumulative dose and severe GU toxicity. Based on these findings, bladder D2 cc should be below 70 Gy and urethral V100 below 0.40 cc.</description><subject>Aged</subject><subject>Brachytherapy - adverse effects</subject><subject>Brachytherapy - methods</subject><subject>Dosimetry</subject><subject>Focal salvage</subject><subject>GU toxicity</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>I125 brachytherapy</subject><subject>Iodine Radioisotopes - therapeutic use</subject><subject>Male</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - radiotherapy</subject><subject>Radiation Injuries - prevention &amp; control</subject><subject>Radiometry</subject><subject>Radiotherapy Dosage</subject><subject>Salvage Therapy - methods</subject><subject>Total salvage</subject><subject>Urethra - radiation effects</subject><subject>Urinary Bladder - radiation effects</subject><issn>0167-8140</issn><issn>1879-0887</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUuPFCEUhYnROO3oPzCGpZsqeVVRuDAxEx-TdOJCZ00ouNi01UUL9MRa-del7NaFG1cQOPfce7-D0HNKWkpo_2rfJuPibFtGaNeSoSV0eIA2dJCqIcMgH6JNlclmoIJcoSc57wkhjHD5GF2xngvVKbJBP-8SlF0yEzazw-NknIOEXczhACUtOHpcYrl8-2jrLZvp3nwFfBtdmKGhrMPHFHMxBfCYjN0tZQfJHJfXeLu-lfgj2FCW3xbVGbCNcy7JhLnkp-iRN1OGZ5fzGt29f_fl5mOz_fTh9ubttrFdx0vTj1JILkYurFHSOzXAaKTpBBiqevDE994zQUYDvQTGGedKuV444TlThvFr9PLsW0f9foJc9CFkC9NkZoinrKkUqq_sqKxScZbaulVO4PUxhYNJi6ZEr-j1Xp_R6xW9JoOu6GvZi0uH03gA97foD-sqeHMWQN3zPkDS2QaYLbiQwBbtYvhfh38N7BTmUDP5BgvkfTyluTLUVGemif68xr-mTztChOCE_wJU9a1t</recordid><startdate>20151101</startdate><enddate>20151101</enddate><creator>Peters, Max</creator><creator>van der Voort van Zyp, Jochem</creator><creator>Hoekstra, Carel</creator><creator>Westendorp, Hendrik</creator><creator>van de Pol, Sandrine</creator><creator>Moerland, Marinus</creator><creator>Maenhout, Metha</creator><creator>Kattevilder, Rob</creator><creator>van Vulpen, Marco</creator><general>Elsevier Ireland Ltd</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></search><sort><creationdate>20151101</creationdate><title>Urethral and bladder dosimetry of total and focal salvage Iodine-125 prostate brachytherapy: Late toxicity and dose constraints</title><author>Peters, Max ; van der Voort van Zyp, Jochem ; Hoekstra, Carel ; Westendorp, Hendrik ; van de Pol, Sandrine ; Moerland, Marinus ; Maenhout, Metha ; Kattevilder, Rob ; van Vulpen, Marco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c553t-6b74734b34ca97fd98eba7a54ea196ef0f6ff240bae67e2323399d64d4f329a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aged</topic><topic>Brachytherapy - adverse effects</topic><topic>Brachytherapy - methods</topic><topic>Dosimetry</topic><topic>Focal salvage</topic><topic>GU toxicity</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>I125 brachytherapy</topic><topic>Iodine Radioisotopes - therapeutic use</topic><topic>Male</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - radiotherapy</topic><topic>Radiation Injuries - prevention &amp; control</topic><topic>Radiometry</topic><topic>Radiotherapy Dosage</topic><topic>Salvage Therapy - methods</topic><topic>Total salvage</topic><topic>Urethra - radiation effects</topic><topic>Urinary Bladder - radiation effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Peters, Max</creatorcontrib><creatorcontrib>van der Voort van Zyp, Jochem</creatorcontrib><creatorcontrib>Hoekstra, Carel</creatorcontrib><creatorcontrib>Westendorp, Hendrik</creatorcontrib><creatorcontrib>van de Pol, Sandrine</creatorcontrib><creatorcontrib>Moerland, Marinus</creatorcontrib><creatorcontrib>Maenhout, Metha</creatorcontrib><creatorcontrib>Kattevilder, Rob</creatorcontrib><creatorcontrib>van Vulpen, Marco</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><jtitle>Radiotherapy and oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Peters, Max</au><au>van der Voort van Zyp, Jochem</au><au>Hoekstra, Carel</au><au>Westendorp, Hendrik</au><au>van de Pol, Sandrine</au><au>Moerland, Marinus</au><au>Maenhout, Metha</au><au>Kattevilder, Rob</au><au>van Vulpen, Marco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Urethral and bladder dosimetry of total and focal salvage Iodine-125 prostate brachytherapy: Late toxicity and dose constraints</atitle><jtitle>Radiotherapy and oncology</jtitle><addtitle>Radiother Oncol</addtitle><date>2015-11-01</date><risdate>2015</risdate><volume>117</volume><issue>2</issue><spage>262</spage><epage>269</epage><pages>262-269</pages><issn>0167-8140</issn><eissn>1879-0887</eissn><abstract>Abstract Introduction Salvage Iodine-125 brachytherapy (I-125-BT) constitutes a curative treatment approach for patients with organ-confined recurrent prostate cancer after primary radiotherapy. Currently, focal salvage (FS) instead of whole-gland or total salvage (TS) is being investigated, to reduce severe toxicity associated with cumulative radiation dose. Differences in urethral and bladder dosimetry and constraints to reduce late (&gt;90 days) genitourinary (GU) toxicity are presented here. Materials and methods Dosimetry on intraoperative ultrasound (US) of 20 FS and 28 TS patients was compared. The prostate, bladder, urethra and bulbomembranous (BM) urethra were delineated. Toxicity was assessed using the CTCAE version 4.0. Dose constraints to reduce toxicity in TS patients were evaluated with receiver operating characteristic (ROC) analysis. Results FS I-125 BT significantly reduces bladder and urethral dose compared to TS. Grade 3 GU toxicity occurred once in the FS group. For TS patients late severe (⩾grade 3) GU toxicity was frequent (38% in the total 61 patients and 56% in the 27 analyzed patients). TS patients with ⩾grade 3 GU toxicity showed higher bladder D2 cc than TS patients without toxicity (median 43 Gy) ( p = 0.02). The urethral V100 was significantly higher in TS patients with several toxicity profiles: ⩾grade 3 urethral strictures, ⩾grade 2 urinary retention and multiple ⩾grade 2 GU toxicity events. Dose to the BM urethra did not show a relation with stricture formation. ROC-analysis indicated a bladder D2 cc &lt;70 Gy to prevent ⩾grade 3 GU toxicity (AUC 0.76, 95%CI: 0.56–0.96, p = 0.02). A urethral V100 &lt;0.40 cc (AUC from 0.73–0.91, p = 0.003–0.05) could prevent other late GU toxicity. Conclusion FS I-125 BT reduces urethral and bladder dose significantly compared to TS. With TS, there is an increased risk of cumulative dose and severe GU toxicity. Based on these findings, bladder D2 cc should be below 70 Gy and urethral V100 below 0.40 cc.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>26349590</pmid><doi>10.1016/j.radonc.2015.08.018</doi><tpages>8</tpages></addata></record>
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source MEDLINE; Elsevier ScienceDirect Journals Complete
subjects Aged
Brachytherapy - adverse effects
Brachytherapy - methods
Dosimetry
Focal salvage
GU toxicity
Hematology, Oncology and Palliative Medicine
Humans
I125 brachytherapy
Iodine Radioisotopes - therapeutic use
Male
Prostate cancer
Prostatic Neoplasms - radiotherapy
Radiation Injuries - prevention & control
Radiometry
Radiotherapy Dosage
Salvage Therapy - methods
Total salvage
Urethra - radiation effects
Urinary Bladder - radiation effects
title Urethral and bladder dosimetry of total and focal salvage Iodine-125 prostate brachytherapy: Late toxicity and dose constraints
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