Assessment of the Second Cancer Risk after Prostate Cancer Treatment: Comparison of 3D Conformal Radiotherapy and Intensity Modulated Radiotherapy

Document Type : Original Paper


1 Physics Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt.

2 Radiotherapy Department, National Cancer Institute, Faculty of Medicine, Cairo University, Giza, Egypt

3 Physics Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt


Introduction: Radiation-induced secondary primary cancer is one of the significant late side effects and an undesired outcome of radiotherapy that can be observed in long-term cancer survivors. The present study aimed to estimate the risk of second cancer risk after Three-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) for early stage prostate cancer patient.
Material and Methods: In this study, 10 patients with early stage prostate cancer have been chosen. Three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT) plans were designed. The organ equivalent dose (OED) was calculated based on linear, linear-exponential, and plateau dose-response models. The Second cancer risks (SCR) were estimated by Excess absolute risk (EAR).
Results: The target dose coverage parameters were significantly improved in IMRT compared to 3DCRT. The rectum and bladder mean dose DMean, V50Gy% and V40Gy % were significantly decreased with IMRT. The maximum dose (DMax), DMean, V30Gy % and V20Gy % for head of femurs significantly decreased with IMRT plans. However, the colon DMean significantly increased with in IMRT compared with 3DCRT. The IMRT plans were decreased SCR for the rectum by 10%, 26.6% and 19.5% for linear, plateau and linear-exponential dose- response models respectively. The bladder second cancer risk was decreased by 14% with linear dose-response model in comparison to 3DCRT plans. However, the second cancer risk for colon was significantly increased in average by 91.2% with IMRT plans.
Conclusion: IMRT technique demonstrated a clear advantage in dose coverage, conformity, and homogeneity over 3DCRT and was superior in terms of OAR-sparing. The Second cancer risk for in field organs (rectum and bladder) was decreased with IMRT compared 3DCRT plan.


Main Subjects

  1. Rawla, “Epidemiology of Prostate Cancer,” vol. 10, no. 2, pp. 63–89, 2019.
  2. Sung et al., “Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries,” CA. Cancer J. Clin., vol. 71, no. 3, pp. 209–249, 2021.
  3. Sountoulides, N. Koletsas, D. Kikidakis, K. Paschalidis, and N. Sofikitis, “Secondary malignancies following radiotherapy for prostate cancer.,” Ther. Adv. Urol., vol. 2, no. 3, pp. 119–125, 2010.
  4. Salonia, G. Castagna, P. Capogrosso, F. Castiglione, A. Briganti, and F. Montorsi, “Prevention and management of post prostatectomy erectile dysfunction,” Transl. Androl. Urol., vol. 4, no. 4, p. 421, 2015.
  5. W. Fischer-valuck, Y. J. Rao, and J. M. Michalski, “Intensity-modulated radiotherapy for prostate cancer,” vol. 7, no. I, pp. 297–307, 2018.
  6. Uysal et al., “Dosimetric evaluation of intensity modulated radiotherapy and 4-field 3-D conformal radiotherapy in prostate cancer treatment,” Balkan Med. J., vol. 30, no. 1, p. 54, 2013.
  7. Maric, S. Lukic, M. Mijailovic, L. T. Latinovic, M. Zigic, and P. Banovic, “Dosimetric Comparison: Intensity Modulated Radiation Therapy Vs. 3D Conformal Radiotherapy In Prostate Cancer Radical Treatment,” Serbian J. Exp. Clin. Res.
  8. M. Michalski et al., “Preliminary toxicity analysis of 3-dimensional conformal radiation therapy versus intensity modulated radiation therapy on the high-dose arm of the Radiation Therapy Oncology Group 0126 prostate cancer trial,” Int. J. Radiat. Oncol. Biol. Phys., vol. 87, no. 5, pp. 932–938, 2013.
  9. I. J. Z. Elefsky et al., “Incidence of Late Rectal and Urinary Toxicities after Three- Dimensional Conformal Radiotherapy and Intensity-Modulated Radiotherapy for Localized Prostate Cancer Acute symptoms,” vol. 70, no. 4, pp. 1124–1129, 2008.
  10. J. Hall and C.-S. Wuu, “Radiation-induced second cancers: the impact of 3D-CRT and IMRT,” Int. J. Radiat. Oncol. Biol. Phys., vol. 56, no. 1, pp. 83–88, 2003.
  11. F. Kry et al., “The calculated risk of fatal secondary malignancies from intensity-modulated radiation therapy,” Int. J. Radiat. Oncol. Biol. Phys., vol. 62, no. 4, pp. 1195–1203, 2005.
  12. C. Lillicrap, H. M. Morgan, and J. T. Shakeshaft, “X-ray leakage during radiotherapy,” Br. J. Radiol., vol. 73, no. 871, pp. 793–794, 2000.
  13. Protection, “ICRP publication 103,” Ann ICRP, vol. 37, no. 2.4, p. 2, 2007.
  14. [14] R. Council, “Health risks from exposure to low levels of ionizing radiation: BEIR VII phase 2,” 2006.
  15. UNSCotEoA, “Effects of ionizing radiation: UNSCEAR 2006 Report to the General Assembly, with scientific annexes.” United nations publications, 2009.
  16. A. Schauer and O. W. Linton, “NCRP report No. 160, ionizing radiation exposure of the population of the United States, medical exposure—are we doing less with more, and is there a role for health physicists?,” Health Phys., vol. 97, no. 1, pp. 1–5, 2009.
  17. R. H. Aghdam, H. R. Baghani, and A. H. Aghdam, “Cancer risk incidence from hypothetical accident of VVER-1000 nuclear power plant based on BEIR VII model,” J. Radiother. Pract., vol. 17, no. 2, pp. 212–218, 2018.
  18. R. Baghani, S. R. Mahdavi, and S. M. R. Aghamiri, “Cancer Risk Assessment due to Accidental Exposure inside Neutron Laboratories using BEIR VII Model,” Iran. J. Med. Phys., vol. 15, no. 4, pp. 251–255, 2018.
  19. W. E. S. Chneider, D. A. Z. Wahlen, D. I. R. Oss, B. A. K. A. Otz, and D. R. M. E. D. V Et, “Estimation o Radiation-Induced Cancer from Three-Dimensional Dose Distributions : Concept of Organ Equivalent Dose,” Vol. 61, No. 5, pp. 1510–1515, 2005.
  20. Murray, A. Henry, P. Hoskin, F.-A. Siebert, J. Venselaar, and P. group of the G. E. C. ESTRO, “Second primary cancers after radiation for prostate cancer: a systematic review of the clinical data and impact of treatment technique,” Radiother. Oncol., vol. 110, no. 2, pp. 213–228, 2014.
  21. J. D. Wallis et al., “Second malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis,” bmj, vol. 352, 2016.
  22. Moon, G. J. Stukenborg, J. Keim, and D. Theodorescu, “Cancer incidence after localized therapy for prostate cancer,” Cancer Interdiscip. Int. J. Am. Cancer Soc., vol. 107, no. 5, pp. 991–998, 2006.
  23. Sountoulides, N. Koletsas, D. Kikidakis, K. Paschalidis, and N. Sofikitis, “Secondary malignancies following radiotherapy for prostate cancer,” Ther. Adv. Urol., vol. 2, no. 3, pp. 119–125, 2010.
  24. Schneider, A. Lomax, and N. Lombriser, “Comparative risk assessment of secondary cancer incidence after treatment of Hodgkin’s disease with photon and proton radiation,” Radiat. Res., vol. 154, no. 4, pp. 382–388, 2000.
  25. A. Lindsay, E. G. Wheldon, C. Deehan, and T. E. Wheldon, “Radiation carcinogenesis modelling for risk of treatment-related second tumours following radiotherapy,” Br. J. Radiol., vol. 74, no. 882, pp. 529–536, 2001.
  26. Miralbell, A. Lomax, L. Cella, and U. Schneider, “Potential reduction of the incidence of radiation-induced second cancers by using proton beams in the treatment of pediatric tumors,” Int. J. Radiat. Oncol. Biol. Phys., vol. 54, no. 3, pp. 824–829, 2002.
  27. Schneider, D. Zwahlen, D. Ross, and B. Kaser-Hotz, “Estimation of radiation-induced cancer from three-dimensional dose distributions: Concept of organ equivalent dose,” Int. J. Radiat. Oncol. Biol. Phys., vol. 61, no. 5, pp. 1510–1515, 2005.
  28. J. Murray et al., “Radiation-induced second primary cancer risks from modern external beam radiotherapy for early prostate cancer: impact of stereotactic ablative radiotherapy (SABR), volumetric modulated arc therapy (VMAT) and flattening filter free (FFF) radiotherapy,” Phys. Med. Biol., vol. 60, no. 3, p. 1237, 2015.
  29. Haciislamoglu et al., “Estimation of secondary cancer risk after radiotherapy in high‐risk prostate cancer patients with pelvic irradiation,” J. Appl. Clin. Med. Phys., vol. 21, no. 9, pp. 82–89, 2020.
  30. B. Amin, D. W. Bruner, G. P. Swanson, D. Hunt, R. W. Lee, and D. Low, “A phase III randomized study of hypofractionated 3D-CRT/IMRT versus conventionally fractionated 3D-CRT/IMRT in patients with favorable-risk prostate cancer: the study of RTOG 0415,” Study Chairs, vol. 9, 2007.
  31. Van’t Riet, A. C. A. Mak, M. A. Moerland, L. H. Elders, and W. van der Zee, “A conformation number to quantify the degree of conformality in brachytherapy and external beam irradiation: application to the prostate,” Int. J. Radiat. Oncol. Biol. Phys., vol. 37, no. 3, pp. 731–736, 1997.
  32. Weyh, A. Konski, A. Nalichowski, J. Maier, and D. Lack, “Lung SBRT: Dosimetric and delivery comparison of rapidarc, tomotherapy, and IMRT,” J. Appl. Clin. Med. Phys., vol. 14, no. 4, pp. 3–13, 2013.
  33. Schneider, M. Sumila, and J. Robotka, “Site-specific dose-response relationships for cancer induction from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy,” pp. 1–21, 2011.
  34. R. Zwahlen, J. M. Martin, J. L. Millar, and U. Schneider, “Effect of radiotherapy volume and dose on secondary cancer risk in stage I testicular seminoma,” Int. J. Radiat. Oncol. Biol. Phys., vol. 70, no. 3, pp. 853–858, 2008.
  35. R. Zwahlen, J. D. Ruben, P. Jones, F. Gagliardi, J. L. Millar, and U. Schneider, “Effect of intensity-modulated pelvic radiotherapy on second cancer risk in the postoperative treatment of endometrial and cervical cancer,” Int. J. Radiat. Oncol. Biol. Phys., vol. 74, no. 2, pp. 539–545, 2009.
  36. C. Wortel et al., “Acute toxicity after image-guided intensity modulated radiation therapy compared to 3D conformal radiation therapy in prostate cancer patients,” Int. J. Radiat. Oncol. Biol. Phys., vol. 91, no. 4, pp. 737–744, 2015.
  37. Shirani Tak Abi et al., “Assessment and Comparison of Homogeneity and Conformity Indexes in Step-and-Shoot, Compensator-Based Intensity Modulated Radiation Therapy (IMRT) and Three-Dimensional Conformal Radiation Therapy (3D CRT) in Prostate Cancer,” Iran. J. Med. Phys., vol. 15, no. Special Issue-12th. Iranian Congress of Medical Physics, p. 406, 2018.
  38. ADENEYE et al., “Dosimetric Evaluation of Intensity Modulated Radiotherapy and Three-Dimensional Conformal Radiotherapy Treatment Plans for Prostate Cancer,” TURKISH J. Oncol., vol. 36, no. 1, 2021.
  39. J. Hall and C.-S. Wuu, “Radiation-induced second cancers: the impact of 3D-CRT and IMRT.,” Int. J. Radiat. Oncol. Biol. Phys., vol. 56, no. 1, pp. 83–8, May 2003.
  40. K. Chaturvedi et al., “Second cancers among 104760 survivors of cervical cancer: evaluation of long-term risk,” J. Natl. Cancer Inst., vol. 99, no. 21, pp. 1634–1643, 2007.
  41. F. de Boer, Y. Kumek, W. Jaggernauth, and M. B. Podgorsak, “The effect of beam energy on the quality of IMRT plans for prostate conformal radiotherapy.,” Technol. Cancer Res. Treat., vol. 6, no. 2, pp. 139–146, Apr. 2007.
  42. Yu et al., “The effectiveness of intensity modulated radiation therapy versus three-dimensional radiation therapy in prostate cancer: A meta-analysis of the literatures,” PLoS One, vol. 11, no. 5, p. e0154499, 2016.
  43. Cakir, Z. Akgun, M. Fayda, and F. Agaoglu, “Comparison of three dimensional conformal radiation therapy, intensity modulated radiation therapy and volumetric modulated arc therapy for low radiation exposure of normal tissue in patients with prostate cancer,” Asian Pacific J. Cancer Prev., vol. 16, no. 8, pp. 3365–3370, 2015.
  44. Athiyaman, A. Mayilvaganan, A. Chougule, M. Joan, and H. S. Kumar, “Estimation of radiation-induced second cancer risk associated with the institutional field matching craniospinal irradiation technique: A comparative treatment planning study,” Reports Pract. Oncol. Radiother., vol. 24, no. 5, pp. 409–420, 2019.
  45. Stathakis, J. Li, and C. C. M. Ma, “Monte Carlo determination of radiation‐induced cancer risks for prostate patients undergoing intensity‐modulated radiation therapy,” J. Appl. Clin. Med. Phys., vol. 8, no. 4, pp. 14–27, 2007.
  46. D. Ruben et al., “The Effect of Intensity-Modulated Radiotherapy on Radiation-Induced Second Malignancies,” Int. J. Radiat. Oncol. Biol. Phys., vol. 70, no. 5, pp. 1530–1536, 2008.
  47. M. Howell, S. B. Scarboro, S. F. Kry, and D. Z. Yaldo, “Accuracy of out-of-field dose calculations by a commercial treatment planning system,” Phys. Med. Biol., vol. 55, no. 23, p. 6999, 2010.
  48. Cho, T. Suh, J. Park, and J. Lee, “Practical Implementation of a Collapsed Cone Convolution Algorithm for a,” vol. 61, no. 12, pp. 2073–2083, 2012.
  49. Schneider, A. Lomax, J. Besserer, P. Pemler, N. Lombriser, and B. Kaser-Hotz, “The impact of dose escalation on secondary cancer risk after radiotherapy of prostate cancer,” Int. J. Radiat. Oncol. Biol. Phys., vol. 68, no. 3, pp. 892–897, 2007.
  50. D. Ruben et al., “The effect of intensity-modulated radiotherapy on radiation-induced second malignancies,” Int. J. Radiat. Oncol. Biol. Phys., vol. 70, no. 5, pp. 1530–1536, 2008.
  51. R. Filippi et al., “Intensity modulated radiation therapy and second cancer risk in adults,” Int. J. Radiat. Oncol. Biol. Phys., vol. 100, no. 1, pp. 17–20, 2018.
  52. Qiu, V. Moiseenko, C. Aquino-Parsons, and C. Duzenli, “Equivalent doses for gynecological patients undergoing IMRT or RapidArc with kilovoltage cone beam CT,” Radiother. Oncol., vol. 104, no. 2, pp. 257–262, 2012.
  53. Ardenfors, D. Josefsson, and A. Dasu, “Are IMRT treatments in the head and neck region increasing the risk of secondary cancers?,” Acta Oncol. (Madr)., vol. 53, no. 8, pp. 1041–1047, 2014.






Volume 19, Issue 4
July and August 2022
Pages 222-233
  • Receive Date: 15 August 2021
  • Revise Date: 02 January 2022
  • Accept Date: 10 January 2022
  • First Publish Date: 10 January 2022