PRISTINE Trial: PRoton Beam Therapy In Seminoma - Toxicity INvestigation and Evaluation of Outcome

Overview

Stage II seminoma is a type of cancer that is usually highly curable and most often affects young men. Radiotherapy is an effective treatment, but it can sometimes cause side effects in the long term and, rarely, increase the risk of developing another cancer later in life.For this reason, more targeted treatments are being explored, such as proton therapy (PBT). This type of radiotherapy uses protons to better focus the treatment on the tumor while reducing exposure to the surrounding healthy tissues.The goal is to treat the cancer effectively while minimizing side effects as much as possible.

Interventions

• Radiation protontherapy
  patients will be treated with protontherapy instead of radiotherapy with photon as standard of care

Primary outcome measures

• Treatment toxicities [Time frame: from enrollment to two years follow up]
• Progression free survival [Time frame: from enrollment to 12 months from treatment]
• Modeled excess absolute risk (EAR) of secondary malignancies [Time frame: from treatment to two years follow up]

Secondary outcome measures (7)

• Overall survival [Time frame: from treatment to three years follow up]
• Quality of life outcomes [Time frame: from treatment to two years follow up]
• Values of circulating hsa-miR-371a-3p in patient treated with Proton Therapy [Time frame: from treatment to two years follow up]
• Correlation between miRNA clearance/persistance and outcomes [Time frame: from treatment to two years follow up]
• Quantification of immune cell populations according to cell type [Time frame: from treatment to two years follow up]
• Quality of life outcomes [Time frame: from treatment to two years follow up]
• Quality of life outcomes [Time frame: From treatment to two years follow up]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• Male gender
• ECOG Performance status 0 - 1
• Histologically confirmed diagnosis of testicular seminoma
• Stage IIA - IIB disease with metastatic involvement limited to retroperitoneal lymph nodes measuring ≤3 cm in greatest diameter
• Prior radical orchiectomy
• Clinical indication for radiotherapy
• Written informed consent provided

Exclusion criteria

• Non-seminomatous germ cell tumor histology
• Incomplete definitive surgical orchiectomy, including diagnostic biopsy alone
• Prior or concurrent second malignancy other than non-melanoma skin cancer, unless disease free for a minimum of five years
• Prior radiotherapy to the abdominal or pelvic region
• Known severe, active co-morbidity
• Inability or refusal to provide informed consent

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Marelli G, Morina N, Puccio S, Iovino M, Pandini M, Portale F, Carvetta M, Mishra D, Diana E, Meregalli G, Paraboschi E, Cibella J, Peano C, Basso G, De Simone G, Camisaschi C, Magrini E, Sartori G, Karimi E, Colombo P, Lazzeri M, Casale P, Morosi L, Martano G, Asselta R, Bonavita E, Matsunami H, Bertoni F, Walsh L, Lugli E, Di Mitri D. Chemosensor receptors are lipid-detecting regulators of macro PMID 40588561
• Li X, Ding R, Liu Z, Teixeira WMS, Ye J, Tian L, Li H, Guo S, Yao K, Ma Z, Liu Z. A predictive system comprising serum microRNAs and radiomics for residual retroperitoneal masses in metastatic nonseminomatous germ cell tumors. Cell Rep Med. 2024 Dec 17;5(12):101843. doi: 10.1016/j.xcrm.2024.101843. Epub 2024 Dec 12. PMID 39672156
• Alsyouf M, Nappi L, Nichols C, Daneshmand S. Plasma Micro-RNA 371 Expression in Early-Stage Germ Cell Tumors: Are We Ready to Move Toward Biology-Based Decision Making? J Clin Oncol. 2023 May 10;41(14):2478-2482. doi: 10.1200/JCO.22.02002. Epub 2023 Feb 9. No abstract available. PMID 36758194
• Konneh B, Lafin JT, Howard J, Gerald T, Amini A, Savelyeva A, Woldu SL, Lewis CM, Jia L, Margulis V, Coleman N, Scarpini C, Frazier AL, Murray MJ, Amatruda JF, Bagrodia A. Evaluation of miR-371a-3p to predict viable germ cell tumor in patients with pure seminoma receiving retroperitoneal lymph node dissection. Andrology. 2023 May;11(4):634-640. doi: 10.1111/andr.13317. Epub 2022 Nov 2. PMID 36254623
• Nestler T, Schoch J, Belge G, Dieckmann KP. MicroRNA-371a-3p-The Novel Serum Biomarker in Testicular Germ Cell Tumors. Cancers (Basel). 2023 Aug 3;15(15):3944. doi: 10.3390/cancers15153944. PMID 37568759
• Aziz Z, Wagner S, Agyekum A, Pumpalova YS, Prest M, Lim F, Rustgi S, Kastrinos F, Grady WM, Hur C. Cost-Effectiveness of Liquid Biopsy for Colorectal Cancer Screening in Patients Who Are Unscreened. JAMA Netw Open. 2023 Nov 1;6(11):e2343392. doi: 10.1001/jamanetworkopen.2023.43392. PMID 37971743
• Tulik P, Maciak M, Tulik M. A dosimetric comparison of 3D-CRT, IMRT and IMAT treatment techniques - assessment from radiation protection point of view. Rep Pract Oncol Radiother. 2024 Mar 18;29(1):69-76. doi: 10.5603/rpor.99025. eCollection 2024. PMID 39165590
• Pursley J, Remillard K, Depauw N, Lee G, Grassberger C, Paganetti H, Efstathiou JA, Kamran SC. Radiation Therapy for Stage IIA/B Seminoma: Modeling Secondary Cancer Risk for Protons and VMAT versus 3D Photons. Cancers (Basel). 2024 Feb 15;16(4):784. doi: 10.3390/cancers16040784. PMID 38398175

Identifiers

NCT: NCT07601672 · PRO - 2026 - 001 · IG 2025 ID 32742

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗