Kidney Disease in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review

Kidney injury is a known late and potentially devastating complication of abdominal radiation therapy (RT) in pediatric patients. A comprehensive Pediatric Normal Tissue Effects in the Clinic review by the Genitourinary (GU) Task Force aimed to describe RT dose-volume relationships for GU dysfunctio...

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Veröffentlicht in:International journal of radiation oncology, biology, physics biology, physics, 2024-06, Vol.119 (2), p.560-574
Hauptverfasser: Poppe, Matthew M., Tai, An, Li, X. Allen, Miften, Moyed, Olch, Arthur, Marks, Lawrence B., Qureshi, Bilal Mazhar, Spunt, Sheri L., Shnorhavorian, Margarett, Nelson, Geoff, Ronckers, Cecile, Kalapurakal, John, Marples, Brian, Constine, Louis S., Liu, Arthur K.
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container_title International journal of radiation oncology, biology, physics
container_volume 119
creator Poppe, Matthew M.
Tai, An
Li, X. Allen
Miften, Moyed
Olch, Arthur
Marks, Lawrence B.
Qureshi, Bilal Mazhar
Spunt, Sheri L.
Shnorhavorian, Margarett
Nelson, Geoff
Ronckers, Cecile
Kalapurakal, John
Marples, Brian
Constine, Louis S.
Liu, Arthur K.
description Kidney injury is a known late and potentially devastating complication of abdominal radiation therapy (RT) in pediatric patients. A comprehensive Pediatric Normal Tissue Effects in the Clinic review by the Genitourinary (GU) Task Force aimed to describe RT dose-volume relationships for GU dysfunction, including kidney, bladder, and hypertension, for pediatric malignancies. The effect of chemotherapy was also considered. We conducted a comprehensive PubMed search of peer-reviewed manuscripts published from 1990 to 2017 for investigations on RT-associated GU toxicities in children treated for cancer. We retrieved 3271 articles with 100 fulfilling criteria for full review, 24 with RT dose data and 13 adequate for modeling. Endpoints were heterogenous and grouped according to National Kidney Foundation: grade ≥1, grade ≥2, and grade ≥3. We modeled whole kidney exposure from total body irradiation (TBI) for hematopoietic stem cell transplant and whole abdominal irradiation (WAI) for patients with Wilms tumor. Partial kidney tolerance was modeled from a single publication from 2021 after the comprehensive review revealed no usable partial kidney data. Inadequate data existed for analysis of bladder RT-associated toxicities. The 13 reports with long-term GU outcomes suitable for modeling included 4 on WAI for Wilms tumor, 8 on TBI, and 1 for partial renal RT exposure. These reports evaluated a total of 1191 pediatric patients, including: WAI 86, TBI 666, and 439 partial kidney. The age range at the time of RT was 1 month to 18 years with medians of 2 to 11 years in the various reports. In our whole kidney analysis we were unable to include chemotherapy because of the heterogeneity of regimens and paucity of data. Age-specific toxicity data were also unavailable. Wilms studies occurred from 1968 to 2011 with mean follow-ups 8 to 15 years. TBI studies occurred from 1969 to 2004 with mean follow-ups of 4 months to 16 years. We modeled risk of dysfunction by RT dose and grade of toxicity. Normal tissue complication rates ≥5%, expressed as equivalent doses, 2 Gy/fx for whole kidney exposures occurred at 8.5, 10.2, and 14.5 Gy for National Kidney Foundation grades ≥1, ≥2, and ≥3, respectively. Conventional Wilms WAI of 10.5 Gy in 6 fx had risks of ≥grade 2 toxicity 4% and ≥grade 3 toxicity 1%. For fractionated 12 Gy TBI, those risks were 8% and
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Allen ; Miften, Moyed ; Olch, Arthur ; Marks, Lawrence B. ; Qureshi, Bilal Mazhar ; Spunt, Sheri L. ; Shnorhavorian, Margarett ; Nelson, Geoff ; Ronckers, Cecile ; Kalapurakal, John ; Marples, Brian ; Constine, Louis S. ; Liu, Arthur K.</creator><creatorcontrib>Poppe, Matthew M. ; Tai, An ; Li, X. Allen ; Miften, Moyed ; Olch, Arthur ; Marks, Lawrence B. ; Qureshi, Bilal Mazhar ; Spunt, Sheri L. ; Shnorhavorian, Margarett ; Nelson, Geoff ; Ronckers, Cecile ; Kalapurakal, John ; Marples, Brian ; Constine, Louis S. ; Liu, Arthur K.</creatorcontrib><description>Kidney injury is a known late and potentially devastating complication of abdominal radiation therapy (RT) in pediatric patients. A comprehensive Pediatric Normal Tissue Effects in the Clinic review by the Genitourinary (GU) Task Force aimed to describe RT dose-volume relationships for GU dysfunction, including kidney, bladder, and hypertension, for pediatric malignancies. The effect of chemotherapy was also considered. We conducted a comprehensive PubMed search of peer-reviewed manuscripts published from 1990 to 2017 for investigations on RT-associated GU toxicities in children treated for cancer. We retrieved 3271 articles with 100 fulfilling criteria for full review, 24 with RT dose data and 13 adequate for modeling. Endpoints were heterogenous and grouped according to National Kidney Foundation: grade ≥1, grade ≥2, and grade ≥3. We modeled whole kidney exposure from total body irradiation (TBI) for hematopoietic stem cell transplant and whole abdominal irradiation (WAI) for patients with Wilms tumor. Partial kidney tolerance was modeled from a single publication from 2021 after the comprehensive review revealed no usable partial kidney data. Inadequate data existed for analysis of bladder RT-associated toxicities. The 13 reports with long-term GU outcomes suitable for modeling included 4 on WAI for Wilms tumor, 8 on TBI, and 1 for partial renal RT exposure. These reports evaluated a total of 1191 pediatric patients, including: WAI 86, TBI 666, and 439 partial kidney. The age range at the time of RT was 1 month to 18 years with medians of 2 to 11 years in the various reports. In our whole kidney analysis we were unable to include chemotherapy because of the heterogeneity of regimens and paucity of data. Age-specific toxicity data were also unavailable. Wilms studies occurred from 1968 to 2011 with mean follow-ups 8 to 15 years. TBI studies occurred from 1969 to 2004 with mean follow-ups of 4 months to 16 years. We modeled risk of dysfunction by RT dose and grade of toxicity. Normal tissue complication rates ≥5%, expressed as equivalent doses, 2 Gy/fx for whole kidney exposures occurred at 8.5, 10.2, and 14.5 Gy for National Kidney Foundation grades ≥1, ≥2, and ≥3, respectively. Conventional Wilms WAI of 10.5 Gy in 6 fx had risks of ≥grade 2 toxicity 4% and ≥grade 3 toxicity 1%. For fractionated 12 Gy TBI, those risks were 8% and &lt;3%, respectively. Data did not support whole kidney modeling with chemotherapy. Partial kidney modeling from 439 survivors who received RT (median age, 7.3 years) demonstrated 5 or 10 Gy to 100% kidney gave a &lt;5% risk of grades 3 to 5 toxicity with 1500 mg/m2 carboplatin or no chemo. With 480 mg/m2 cisplatin, a 3% risk of ≥grade 3 toxicity occurred without RT and a 5% risk when 26% kidney received ≥10 Gy. With 63 g/m2 of ifosfamide, a 5% risk of ≥grade 3 toxicity occurred with no RT, and a 10% toxicity risk occurred when 42% kidney received ≥10 Gy. In patients with Wilms tumor, the risk of toxicity from 10.5 Gy of WAI is low. For 12 Gy fractionated TBI with various mixtures of chemotherapy, the risk of severe toxicity is low, but low-grade toxicity is not uncommon. Partial kidney data are limited and toxicity is associated heavily with the use of nephrotoxic chemotherapeutic agents. Our efforts demonstrate the need for improved data gathering, systematic follow-up, and reporting in future clinical studies. Current radiation dose used for Wilms tumor and TBI appear to be safe; however, efforts in effective kidney-sparing TBI and WAI regimens may reduce the risks of renal injury without compromising cure.</description><identifier>ISSN: 0360-3016</identifier><identifier>EISSN: 1879-355X</identifier><identifier>DOI: 10.1016/j.ijrobp.2023.02.040</identifier><identifier>PMID: 37452796</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Cancer Survivors ; Child ; Child, Preschool ; Hematopoietic Stem Cell Transplantation - adverse effects ; Humans ; Hypertension - etiology ; Infant ; Kidney - radiation effects ; Kidney Diseases - etiology ; Kidney Neoplasms - radiotherapy ; Neoplasms - drug therapy ; Neoplasms - radiotherapy ; Organs at Risk - radiation effects ; Radiation Injuries - etiology ; Radiotherapy Dosage ; Urinary Bladder - radiation effects ; Whole-Body Irradiation - adverse effects ; Wilms Tumor - drug therapy ; Wilms Tumor - radiotherapy</subject><ispartof>International journal of radiation oncology, biology, physics, 2024-06, Vol.119 (2), p.560-574</ispartof><rights>2023</rights><rights>Copyright © 2023. Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-b0b5c5c5c41553d4f7593a7db071173f063f3492c1ccc4ca2bc16821697c1d213</citedby><cites>FETCH-LOGICAL-c362t-b0b5c5c5c41553d4f7593a7db071173f063f3492c1ccc4ca2bc16821697c1d213</cites><orcidid>0000-0002-9573-1329</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0360301623001979$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37452796$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Poppe, Matthew M.</creatorcontrib><creatorcontrib>Tai, An</creatorcontrib><creatorcontrib>Li, X. Allen</creatorcontrib><creatorcontrib>Miften, Moyed</creatorcontrib><creatorcontrib>Olch, Arthur</creatorcontrib><creatorcontrib>Marks, Lawrence B.</creatorcontrib><creatorcontrib>Qureshi, Bilal Mazhar</creatorcontrib><creatorcontrib>Spunt, Sheri L.</creatorcontrib><creatorcontrib>Shnorhavorian, Margarett</creatorcontrib><creatorcontrib>Nelson, Geoff</creatorcontrib><creatorcontrib>Ronckers, Cecile</creatorcontrib><creatorcontrib>Kalapurakal, John</creatorcontrib><creatorcontrib>Marples, Brian</creatorcontrib><creatorcontrib>Constine, Louis S.</creatorcontrib><creatorcontrib>Liu, Arthur K.</creatorcontrib><title>Kidney Disease in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review</title><title>International journal of radiation oncology, biology, physics</title><addtitle>Int J Radiat Oncol Biol Phys</addtitle><description>Kidney injury is a known late and potentially devastating complication of abdominal radiation therapy (RT) in pediatric patients. 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Partial kidney tolerance was modeled from a single publication from 2021 after the comprehensive review revealed no usable partial kidney data. Inadequate data existed for analysis of bladder RT-associated toxicities. The 13 reports with long-term GU outcomes suitable for modeling included 4 on WAI for Wilms tumor, 8 on TBI, and 1 for partial renal RT exposure. These reports evaluated a total of 1191 pediatric patients, including: WAI 86, TBI 666, and 439 partial kidney. The age range at the time of RT was 1 month to 18 years with medians of 2 to 11 years in the various reports. In our whole kidney analysis we were unable to include chemotherapy because of the heterogeneity of regimens and paucity of data. Age-specific toxicity data were also unavailable. Wilms studies occurred from 1968 to 2011 with mean follow-ups 8 to 15 years. TBI studies occurred from 1969 to 2004 with mean follow-ups of 4 months to 16 years. We modeled risk of dysfunction by RT dose and grade of toxicity. Normal tissue complication rates ≥5%, expressed as equivalent doses, 2 Gy/fx for whole kidney exposures occurred at 8.5, 10.2, and 14.5 Gy for National Kidney Foundation grades ≥1, ≥2, and ≥3, respectively. Conventional Wilms WAI of 10.5 Gy in 6 fx had risks of ≥grade 2 toxicity 4% and ≥grade 3 toxicity 1%. For fractionated 12 Gy TBI, those risks were 8% and &lt;3%, respectively. Data did not support whole kidney modeling with chemotherapy. Partial kidney modeling from 439 survivors who received RT (median age, 7.3 years) demonstrated 5 or 10 Gy to 100% kidney gave a &lt;5% risk of grades 3 to 5 toxicity with 1500 mg/m2 carboplatin or no chemo. With 480 mg/m2 cisplatin, a 3% risk of ≥grade 3 toxicity occurred without RT and a 5% risk when 26% kidney received ≥10 Gy. With 63 g/m2 of ifosfamide, a 5% risk of ≥grade 3 toxicity occurred with no RT, and a 10% toxicity risk occurred when 42% kidney received ≥10 Gy. In patients with Wilms tumor, the risk of toxicity from 10.5 Gy of WAI is low. For 12 Gy fractionated TBI with various mixtures of chemotherapy, the risk of severe toxicity is low, but low-grade toxicity is not uncommon. Partial kidney data are limited and toxicity is associated heavily with the use of nephrotoxic chemotherapeutic agents. Our efforts demonstrate the need for improved data gathering, systematic follow-up, and reporting in future clinical studies. 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Allen</au><au>Miften, Moyed</au><au>Olch, Arthur</au><au>Marks, Lawrence B.</au><au>Qureshi, Bilal Mazhar</au><au>Spunt, Sheri L.</au><au>Shnorhavorian, Margarett</au><au>Nelson, Geoff</au><au>Ronckers, Cecile</au><au>Kalapurakal, John</au><au>Marples, Brian</au><au>Constine, Louis S.</au><au>Liu, Arthur K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kidney Disease in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review</atitle><jtitle>International journal of radiation oncology, biology, physics</jtitle><addtitle>Int J Radiat Oncol Biol Phys</addtitle><date>2024-06-01</date><risdate>2024</risdate><volume>119</volume><issue>2</issue><spage>560</spage><epage>574</epage><pages>560-574</pages><issn>0360-3016</issn><eissn>1879-355X</eissn><abstract>Kidney injury is a known late and potentially devastating complication of abdominal radiation therapy (RT) in pediatric patients. A comprehensive Pediatric Normal Tissue Effects in the Clinic review by the Genitourinary (GU) Task Force aimed to describe RT dose-volume relationships for GU dysfunction, including kidney, bladder, and hypertension, for pediatric malignancies. The effect of chemotherapy was also considered. We conducted a comprehensive PubMed search of peer-reviewed manuscripts published from 1990 to 2017 for investigations on RT-associated GU toxicities in children treated for cancer. We retrieved 3271 articles with 100 fulfilling criteria for full review, 24 with RT dose data and 13 adequate for modeling. Endpoints were heterogenous and grouped according to National Kidney Foundation: grade ≥1, grade ≥2, and grade ≥3. We modeled whole kidney exposure from total body irradiation (TBI) for hematopoietic stem cell transplant and whole abdominal irradiation (WAI) for patients with Wilms tumor. Partial kidney tolerance was modeled from a single publication from 2021 after the comprehensive review revealed no usable partial kidney data. Inadequate data existed for analysis of bladder RT-associated toxicities. The 13 reports with long-term GU outcomes suitable for modeling included 4 on WAI for Wilms tumor, 8 on TBI, and 1 for partial renal RT exposure. These reports evaluated a total of 1191 pediatric patients, including: WAI 86, TBI 666, and 439 partial kidney. The age range at the time of RT was 1 month to 18 years with medians of 2 to 11 years in the various reports. In our whole kidney analysis we were unable to include chemotherapy because of the heterogeneity of regimens and paucity of data. Age-specific toxicity data were also unavailable. Wilms studies occurred from 1968 to 2011 with mean follow-ups 8 to 15 years. TBI studies occurred from 1969 to 2004 with mean follow-ups of 4 months to 16 years. We modeled risk of dysfunction by RT dose and grade of toxicity. Normal tissue complication rates ≥5%, expressed as equivalent doses, 2 Gy/fx for whole kidney exposures occurred at 8.5, 10.2, and 14.5 Gy for National Kidney Foundation grades ≥1, ≥2, and ≥3, respectively. Conventional Wilms WAI of 10.5 Gy in 6 fx had risks of ≥grade 2 toxicity 4% and ≥grade 3 toxicity 1%. For fractionated 12 Gy TBI, those risks were 8% and &lt;3%, respectively. Data did not support whole kidney modeling with chemotherapy. Partial kidney modeling from 439 survivors who received RT (median age, 7.3 years) demonstrated 5 or 10 Gy to 100% kidney gave a &lt;5% risk of grades 3 to 5 toxicity with 1500 mg/m2 carboplatin or no chemo. With 480 mg/m2 cisplatin, a 3% risk of ≥grade 3 toxicity occurred without RT and a 5% risk when 26% kidney received ≥10 Gy. With 63 g/m2 of ifosfamide, a 5% risk of ≥grade 3 toxicity occurred with no RT, and a 10% toxicity risk occurred when 42% kidney received ≥10 Gy. In patients with Wilms tumor, the risk of toxicity from 10.5 Gy of WAI is low. For 12 Gy fractionated TBI with various mixtures of chemotherapy, the risk of severe toxicity is low, but low-grade toxicity is not uncommon. Partial kidney data are limited and toxicity is associated heavily with the use of nephrotoxic chemotherapeutic agents. Our efforts demonstrate the need for improved data gathering, systematic follow-up, and reporting in future clinical studies. Current radiation dose used for Wilms tumor and TBI appear to be safe; however, efforts in effective kidney-sparing TBI and WAI regimens may reduce the risks of renal injury without compromising cure.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>37452796</pmid><doi>10.1016/j.ijrobp.2023.02.040</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-9573-1329</orcidid></addata></record>
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subjects Adolescent
Cancer Survivors
Child
Child, Preschool
Hematopoietic Stem Cell Transplantation - adverse effects
Humans
Hypertension - etiology
Infant
Kidney - radiation effects
Kidney Diseases - etiology
Kidney Neoplasms - radiotherapy
Neoplasms - drug therapy
Neoplasms - radiotherapy
Organs at Risk - radiation effects
Radiation Injuries - etiology
Radiotherapy Dosage
Urinary Bladder - radiation effects
Whole-Body Irradiation - adverse effects
Wilms Tumor - drug therapy
Wilms Tumor - radiotherapy
title Kidney Disease in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review
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