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Development of a National Indication Protocol for Proton Therapy in Patients With Seminoma Testis to Reduce the Risk on Subsequent Primary Cancers

  • Nienke Kuijsters
  • , Peter Sinnige
  • , Pauline A. Bakker
  • , Shafak Al Uwini
  • , Charlotte L. Brouwer
  • , Tom Budiharto
  • , Rob P. Coppes
  • , Maarten Dirkx
  • , Martine Franckena
  • , Steven Habraken
  • , Marianne A.A. de Jong
  • , Yvonne L.B. Klaver
  • , Johannes A. Langendijk
  • , Ada Oele
  • , Erik Schimmel
  • , Ewoud Schuit
  • , Robert Jan Smeenk
  • , Mirko Unipan
  • , Ben Vanneste
  • , Wilma D. Heemsbergen
  • Liesbeth J. Boersma*
*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

PurposeTo develop a National Indication Protocol for Proton therapy (PT) (NIPP) for selecting seminoma testis patients (STPs) for PT in the Netherlands, aiming at reducing the risk of subsequent primary cancers (SPCs).Methods and MaterialsA multidisciplinary workgroup developed criteria for an NIPP based on a systematic literature search. To estimate its potential, PT-photon plan comparisons were constructed for 13 historical patients, after which NIPP version 1 was finalized. First clinical results of NIPP-v1 were evaluated.ResultsFrom cohort studies, it was established that the kidney, pancreas, stomach, and bladder were the main organs at risk contributing to excess SPC risks in STPs treated with radiation therapy. Estimated excess relative risks per 1 Gy increase in mean dose were as follows: kidney, 0.13; pancreas, 0.12; stomach, 0.47; and bladder, 0.50. Combined with absolute lifetime risks from the Dutch male population (age, 30-79 years), the corresponding lifetime absolute excess risks (AERs) per 1 Gy increase were +0.20%, +0.16%, +0.28%, and +0.65%, respectively. A first exploratory analysis in 13 replanned historical patients showed potential for an NIPP, as the required AER reduction of =2% for a grade 4 adverse event was achievable in 11 cases (85%). In a provisional NIPP version 1, criteria were as follows: age =50 years; paraortic and/or para-iliac RT; and no life-threatening comorbidity. In NIPP version 2 (approved and implemented), an estimated lifetime AER reduction of =2% by PT was required as well. From the first 76 PT patients based on NIPP-v1, 71% would qualify for NIPP-v2 as well. In 39 available PT-photon comparisons, we found an average 3.0% (median, 2.9%; IQR, 2.1%) AER reduction by PT.ConclusionsWe defined an NIPP for the selection of STPs for PT in the Netherlands, aimed to reduce the risk of SPC. According to this NIPP, about 75% of these patients qualify for PT. Further studies are required to allow inclusion of nononcological late effects as selection criteria in the NIPP.
Original languageEnglish
JournalInternational Journal of Radiation Oncology Biology Physics
DOIs
Publication statusE-pub ahead of print - 1 Jan 2026

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