Evaluation of NTCP and Second Cancer Induction from Modulated Arc Therapy for High-Risk Prostate Carcinoma by COUPÔLE Software

Document Type : Original Paper

Authors

1 Atomic and Radiologic Physics Department, Physics Division, Nuclear Research Centre of Algiers-Algeria

2 Physics Faculty, HouariBoumedienne University Bab Ezzouar Algiers, Algeria

3 Radiotherapy Oncology Department, Fatima El Azhar Centre Dely Ibrahim, Algiers, Algeria

10.22038/ijmp.2025.81320.2423

Abstract

Introduction: Assessing the toxicity and the risk of radiation-induced secondary cancer is crucial for optimizing treatment planning in prostate carcinoma patients with high risk undergoing Volumetric Modulated Arc Therapy (VMAT). This study aims to evaluate normal tissue complication probability (NTCP) and excess absolute risk (EAR) for different structures (organs at risk, the body). The developed in-house software COUPÔLE was used for toxicity and risk estimation and verified against BIOSUITE. 
Material and Methods: A cohort of twelve randomly selected patients treated with 76 Gy (2 Gy/fraction) using a 6 MV (ELEKTA) treatments were analyzed. Treatments plans were generated using the MONACO system.NTCPs were calculated for rectal bleeding, fecal incontinence and bladder contracture endpoint, while secondary cancer risks were estimated using differents radiobiological models(the Linear Quadratic (LQ), Schneider Linear Exponential and Plateau model) for  rectum, bladder, and whole body. 
Results: NTCP values of 6.6% and 5.7% for rectal bleeding and bladder toxicity (COUPÔLE vs. BIOSUITE) and 5.3% and 5.4% for fecal incontinence. No bladder toxicity was observed. The estimated risk for rectum and bladder (LQ model) were 0.06 (0.02-0.15) and 0.01 (0.0-0.03), respectively. Using the Schneider model, whole-body risk reached 5.40% for V50Gy. The risk was notably higher for the rectum than for the bladder, highlighting the need for further optimization. 
Conclusion: These findings confirm the reliability of COUPÔLE for NTCP and secondary cancer risk estimation, demonstrating its applicability for clinical decision-making in radiation oncology.

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  1. Bufacchi A,Pasciuti K. Rectum and lung normal tissue complication probability: A retrospective analysis depending on different numbers of fractions and different dose-limits. Cancer Rep Rev.2019; 3:1-7.
  2. HamdiCherif M, Zaidi Z, Abdellouche D, Hamdi S, Lakhdari N, DjemaaBendjazia A, et. al. Cancer registry of Setif (Algeria): cancer incidence, trend and survival, 1986–Journal Africain du Cancer/African Journal of Cancer. 2010 ; 2:245-58.
  3. Salah R, HarirN, Zeggai S, Sellam F, Merabent N,Moullessehoul S, and et al.Cancers urologiquesenAlgérie:profilhistoépidémiologique à propos de 348 cas. Journal Africain du Cancer/African Journal of Cancer.2015;2(7):126-31.
  4. Mamgani A, Heemsbergen WD, Peeters ST, Lebesque JV. Role of intensity-modulated radiation-therapy in reducing toxicity in dose escalation for localized prostate cancer. Int J RadiatOncolBiol Phys. 2009;7385.
  5. Tsai CL, Wu JK, Chao HL, Tsai YC, Cheung P, JC. Treatment and dosimetric advantages between VMAT, IMRT, and helical tomotherapy in prostate cancer. Med Dosim.2011;36:264.
  6. Guerrero Urbano MT, Nutting CM. Clinical use of intensity-modulated radiation-therapy: PartI.BJR. 2004; 77:88-96.
  7. Jayapalan Krishnan, Suresh Rao, Sanath Hegde, Jayarama Shetty. Evaluation of healthy Tissue Dose at Different Regions between Volumetric-Modulated Arc Therapy and Intensity-Modulated Radiation Therapy Plans in the Treatment of Various Cancers. JMedPhys.2019;44:213-21.
  8. UneEnzhuo; M Quan, Xiaoqiang Li, YupengLi, Xiaochun Wang, RajatJKudchadker et al. A comprehensive comparison of the quality of IMRT and VMAT plans for the treatment of prostate cancer. Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX, USA. 2012.
  9. Van Dyk J. The modern technology of radiation oncology: A Compendium for medical physicists and radiation oncologists. JMedPhys.1999.
  10. Rajamanickam Baskar, Kuo Ann Lee, Richard Yeo, Kheng-Wei Yeoh. Cancer and Radiation Therapy: Current Advances and Future Directions. Int.J.Med.Sci.2012, 9.
  11. Shuryak I, Sachs RK, Brenner DJ. Cancer risks after radiation exposure in middle age. J Natl Cancer Inst.2010; 102:1628-36.
  12. Lyman JT, Wolbarst AB. Optimization of radiotherapy III: a method of assessing complication probabilities from dose volume histograms. Int J RadiatOncolBiolPhys. 1987;13: 103-109.
  13. Kutcher GJ, Burman C, Brewster L. Histogram reduction method for calculating complication probabilities for three dimentional treatment planning evaluation. Int J RadiationBiolPhys.1991; 21:137-46.
  14. UNSCEAR Sources and Effects of Ionizing Radiation. Report to the General Assembly, with annexes. New York: United Nations: 1993.
  15. Schneider U, Zwahlen D, Ross D, Kaser-Hotz B. Estimation of radiation-induced cancer from three-dimensional dose distributions: concept of organ equivalent dose.Int.J. Radiation Oncology Biol.Phys. 2005;61(5): 1510-5.
  16. Hiram A Gay, Andrzej Niemierko. A free program for calculating EUD based NTCP and TCP in external radiotherapy; Physica Medica. 2007; 23:115-25.
  17. Uzan J, EswarVee C, Malik Z, Nahum AE. Biosuite, new software for radiobiological customization of dose and fraction size in EBRT. Radiotherapy Oncology. 2009; 92(1): s239.
  18. Otto K. Volumetric modulated arc therapy: IMRT in a single gantry arc. Med Phys.2007; 35:310-7.
  19. RTOG 1106/ACRIN 6697, Randomized Phase II Trial of Individualized Adaptive Radiation-therapy Using During-Treatment FDG-PET/CT and Modern Technology in Locally Advanced Non-Small Cell Lung Cancer (NSCLC).
  20. Michel BOLLA, Bruno CHAUVET, Philippe MAINGON, Etienne MARTIN. Guide des Procedures de radiothérapieexterne. 2007; 287-95.
  21. Clements M, Schupp N, Tattersall M, Brown A, Larson R. Monaco treatment planning system tools and optimization processes. Meddos.2018;43(2):1106-17.
  22. ICRU Report 62. Prescribing, recording and reporting photon beam therapy (supplement to ICRU report 50). International Commission on Radiation Units and Measurements; 1999.
  23. The International Commission on Radiation Units and Measurements. In: Journal of the ICRU 10.1 (avr. 2010), NP.2-NP. issn: 1473-6691, 1742-3422. doi 10.1093/jicru/ndq001.url.
  24. Lyman JT. Complication probability as assessed from dose volume histograms. Radiat Res Suppl.1985;104(2s): S13-9.
  25. Yorke ED. Modeling the effect of inhomogeneous dose distributions in normal tissue. Semin Radiat Oncol.2001;11(3):197-209.
  26. Kutcher GJ, Burman C. Calculation of complication probability factors for non uniform normal tissue irradiation: the effective volume method. Int J RadiatOncolBiol Phys. 1989; 16:1623-30.
  27. Uzan J, Nahum AE, Syndikus I. Prostate dose-painting radiotherapy and radiological guided optimization enhances the therapeutic ratio. Clinical Oncology.2016; 28:165-170.
  28. Peeters ST, Hoogeman MS,Heemsbergen WD, Hart AA, Koper PC, Lebesque JV. Rectal bleeding, fecal incontinence, and high Stool frequency after conformal radiation-therapy for prostate cancer: normal tissue complication probability modeling. Int J RadiatOncolBiolPhys. 2006; 66(1):11-9.
  29. Rancati T, Fiorino C, Vavassori. Late rectal bleeding after conformal radiation-therapy for prostate cancer: NTCP modeling. RadiotherOncol. 2008; 88: S332-3.
  30. Burman C, Kutcher GJ, Emami B, Goitein M. Fitting of normal tissue tolerance data to an analytic function.Int J Radiat. Oncol.Biol. Phys. 1991;21(1):123-35.
  31. Dorr W, Hermann T. Second primary tumors after radiation-therapy for malignancies, treatment related to parameters. Stradlater. Onkol.2002; 178:357-62.
  32. hall EJ, WuuCS. Radiation induced second cancers: the impact of 3D-CRT and IMRT. Int J.Radiat.Oncol.Biol.Phys.2003; 56:83-8.
  33. P. Komisopouloos G, Buckey C, Marvoiedi M,Swanson GP et al. Radiobiological evaluation of prostate cancer IMRT and conformal -RTplans using different protocols. Physica Medica.2017; (40);33-41.
  34. Dasu A. Toma-Dasu I. Dose-effect models for risk-relationship to cell survival parameters. ActaOncol. 2005; 44: 829-35.
  35. Schneider U, Sumila M, Robotka J. Site-specific dose-response relationships for cancer induction from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiation-therapy. Theoritical Biology and Medical Modelling.2011; 8:1-21.
  36. Uwe Schneider, linda Walsh. Cancer risk estimates from the combined Japanese A-Bomb and Hodgkin cohorts for doses relevant to radiotherapy. Radiat Environ biophys(2008)47:253-263. Doi: 10.1007/s00411-007-0151-y.
  37. Schneider U, Kaser-Hotz B. A simple dose response relation-ship for modeling secondary cancer incidence after radiotherapy, Z Med Phys.2005; 15:31-37
  38. Schneider U, Lomax A, Besserer J, Pemler P, Lombriser N, Kaser-Hotz B. The impact of dose escalation on secondary cancer risk after radiotherapy of prostate cancer. Int.J. Radiation Oncology Biol.Phys. 2007; 68(3):892-7.
  39. Dasu A. Toma-Dasu. Models for the risk of secondary cancers from radiotherapy. Phys.Med.2017; 42:232-8.
  40. Schneider U, Pemler P, Besserer J, et al. Estimation of radiation induced secondary cancer incidence for radiation-therapy treatment planning. Abstracts of the 15th Annual NASA: Space Radiation Health Investigator’s Workshop. NASA: Port Jefferson, NJ; 2004;58.
  41. Rehman JU, Isa M, Ahmad N, Nasar G, Asghar HN, Gilani ZA, et al. Dosimetric, Radiobiological and Secondary Cancer Risk Evaluation in Head-and-Neck Three-dimensional Conformal Radiation Therapy, Intensity-Modulated Phys.2018; 43(2):129-35.
  42. Bentzen SM, Constine LS, Deasy JO, Eisbruch A, Jackson A, Marks LB, et al. Quantitative analysis of normal tissue effects in the clinic “QUANTEC”: An introduction to the scientific issues. Int.J.Radiation Oncology Biol. Phys.2010;76(3):s3-9.
  43. Clemente‐Gutiérrez F, Pérez‐Vara C, Clavo‐Herranz MH, López‐Carrizosa C, Pérez‐Regadera J, Ibáñez‐Villoslada C. Assessment of radiobiological metrics applied to Patient-specifica process of VMAT prostate treatments. Journal of applied clinical medical physics. 2016;17(2): 341–
  44. Dasu A, Toma Dasu I, Ollofsson J, Karlson M. The use of risk estimation models for the induction of secondary cancers following radiation-therapy. ActaOncol,2005; 44(4):339-47
  45. Mazonakis M, Kachris S, Damilakis J. Secondary bladder and rectal cancer risk estimates following standard fractionated and moderately hypo-fractionated VMAT for prostate carcinoma. Medical Physics. 2020; 47(7): 2805–13.
  46. Demoor-Goldschmidt C, de Vathaire F. Review of risk factors of secondary cancers among cancer among cancer survivors. The British journal of radiology. 2019;92(1093):20180390.