Vol 27, No 1 (2022)
Research paper
Published online: 2022-01-27

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Tomotherapy-based moderate hypofractionation for localized prostate cancer: a mono-institutional analysis

Maria Valentina Tenti1, Gianluca Ingrosso1, Vittorio Bini2, Cristina Mariucci3, Simonetta Saldi4, Emanuele Alì1, Claudio Zucchetti5, Rita Bellavita4, Cynthia Aristei1
Rep Pract Oncol Radiother 2022;27(1):142-151.


Background: To date, few studies have been published on image-guided helical tomotherapy (HT) in a moderate hypofractionation of localized PCa. We report outcome and toxicity of localized PCa patients treated with HT-based moderate hypofractionated radiotherapy.

Materials and methods: 76 patients were retrospectively analyzed. A total dose of 60 Gy (20 x 3 Gy) or 67.5 Gy (25 x 2.7 Gy) was prescribed. The Chi2 test was used to analyze associations between toxicity and dosimetric and clinical parameters. The Cox proportional hazard regression model was used for multivariate analysis. Kaplan-Meier method was used for survival analysis.

Results: median follow-up was 42.26 months [interquartile (IQR), 23–76). At 4-year, overall survival (OS) and metastasis-free survival (MFS) were 91% and 89%, respectively. At multivariate analysis, smoking habitude was associated with MFS [hazard ratio (HR) 7.32, 95% CI: 1.57–34.16, p = 0.011]. Acute and late grade ≥ 2 gastro-intestinal (GI) toxicity was observed in 6.5% and 2.6% of patients, respectively. Acute and late grade ≥ 2 genito-urinary (GU) toxicity were 31.5% and 3.9%. Four-year late GI and GU grade ≥ 2 toxicity were 3% and 7%, respectively. Acute GI toxicity was associated with statins medication (p = 0.04) and androgen deprivation therapy (p = 0.013). Acute GU toxicity was associated with the use of anticoagulants (p = 0.029) and antiaggregants (p = 0.013).

Conclusions: HT-based moderate hypofractionation shows very low rates of toxicity. Smoking habitude is associated with the risk of developing metastases after radical treatment for localized PCa.

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  1. Hamdy F, Donovan J, Lane J, et al. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N Engl J Med. 2016; 375(15): 1415–1424.
  2. Pollack A, Walker G, Horwitz EM, et al. Randomized trial of hypofractionated external-beam radiotherapy for prostate cancer. J Clin Oncol. 2013; 31(31): 3860–3868.
  3. Arcangeli G, Saracino B, Arcangeli S, et al. Moderate Hypofractionation in High-Risk, Organ-Confined Prostate Cancer: Final Results of a Phase III Randomized Trial. J Clin Oncol. 2017; 35(17): 1891–1897.
  4. Dearnaley D, Syndikus I, Mossop H, et al. CHHiP Investigators. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol. 2016; 17(8): 1047–1060.
  5. Catton CN, Lukka H, Gu CS, et al. Randomized Trial of a Hypofractionated Radiation Regimen for the Treatment of Localized Prostate Cancer. J Clin Oncol. 2017; 35(17): 1884–1890.
  6. van den Bergh RCN, O'Hanlon S, Cornford P, et al. EAU-EANM-ESTRO-ESUR-SIOG Guideline Panel on Prostate Cancer. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer-2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2021; 79(2): 243–262.
  7. Sanda MG, Cadeddu JA, Kirkby E, et al. Clinically Localized Prostate Cancer: AUA/ASTRO/SUO Guideline. Part I: Risk Stratification, Shared Decision Making, and Care Options. J Urol. 2018; 199(3): 683–690.
  8. Ferrera G, Mortellaro G, Mannino M, et al. Moderate hypofractionation and simultaneous integrated boost by helical tomotherapy in prostate cancer: monoinstitutional report of acute tolerability assessment with different toxicity scales. Radiol Med. 2015; 120(12): 1170–1176.
  9. Cuccia F, Mortellaro G, Trapani G, et al. Acute and late toxicity and preliminary outcomes report of moderately hypofractionated helical tomotherapy for localized prostate cancer: a mono-institutional analysis. Radiol Med. 2020; 125(2): 220–227.
  10. Cekani E, López-Guerra JL, Barrientos R, et al. Late toxicity for prostate cancer patients treated with hypofractionated helical tomotherapy. Rep Pract Oncol Radiother. 2019; 24(3): 298–305.
  11. Epstein JI, Egevad L, Amin MB, et al. Grading Committee. The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System. Am J Surg Pathol. 2016; 40(2): 244–252.
  12. Saldi S, Bellavita R, Lancellotta V, et al. Acute Toxicity Profiles of Hypofractionated Adjuvant and Salvage Radiation Therapy After Radical Prostatectomy: Results of a Prospective Study. Int J Radiat Oncol Biol Phys. 2019; 103(1): 105–111.
  13. Ghadjar P, Zelefsky MJ, Spratt DE, et al. Impact of dose to the bladder trigone on long-term urinary function after high-dose intensity modulated radiation therapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2014; 88(2): 339–344.
  14. Murray J, Griffin C, Gulliford S, et al. CHHiP Investigators. A randomised assessment of image guided radiotherapy within a phase 3 trial of conventional or hypofractionated high dose intensity modulated radiotherapy for prostate cancer. Radiother Oncol. 2020; 142: 62–71.
  15. Lieng H, Pintilie M, Bayley A, et al. Long-term outcomes of a phase II trial of moderate hypofractionated image-guided intensity modulated radiotherapy (IG-IMRT) for localized prostate cancer. Radiother Oncol. 2017; 122(1): 93–98.
  16. Citrin DE. Recent Developments in Radiotherapy. N Engl J Med. 2017; 377(11): 1065–1075.
  17. Haydont V, Bourgier C, Pocard M, et al. Pravastatin Inhibits the Rho/CCN2/extracellular matrix cascade in human fibrosis explants and improves radiation-induced intestinal fibrosis in rats. Clin Cancer Res. 2007; 13(18 Pt 1): 5331–5340.
  18. Nübel T, Damrot J, Roos WP, et al. Lovastatin protects human endothelial cells from killing by ionizing radiation without impairing induction and repair of DNA double-strand breaks. Clin Cancer Res. 2006; 12(3 Pt 1): 933–939.
  19. Haydont V, Gilliot O, Rivera S, et al. Successful mitigation of delayed intestinal radiation injury using pravastatin is not associated with acute injury improvement or tumor protection. Int J Radiat Oncol Biol Phys. 2007; 68(5): 1471–1482.
  20. Palumbo I, Matrone F, Montesi G, et al. Statins Protect Against Acute RT-related Rectal Toxicity in Patients with Prostate Cancer: An Observational Prospective Study. Anticancer Res. 2017; 37(3): 1453–1457.
  21. Mangoni M, Sottili M, Gerini C, et al. Protective Effect of Leuprorelin on Radiation-induced Intestinal Toxicity. Anticancer Res. 2015; 35(7): 3875–3884.
  22. Choe KS, Jani AB, Liauw SL. External beam radiotherapy for prostate cancer patients on anticoagulation therapy: how significant is the bleeding toxicity? Int J Radiat Oncol Biol Phys. 2010; 76(3): 755–760.
  23. Valdagni R, Rancati T, Fiorino C, et al. Development of a set of nomograms to predict acute lower gastrointestinal toxicity for prostate cancer 3D-CRT. Int J Radiat Oncol Biol Phys. 2008; 71(4): 1065–1073.
  24. Ingrosso G, Carosi A, di Cristino D, et al. Volumetric image-guided highly conformal radiotherapy of the prostate bed: Toxicity analysis. Rep Pract Oncol Radiother. 2017; 22(1): 64–70.
  25. Mathieu R, Arango JD, Beckendorf V, et al. Nomograms to predict late urinary toxicity after prostate cancer radiotherapy. World J Urol. 2014; 32(3): 743–751.
  26. Takeda K, Ogawa Y, Ariga H, et al. Clinical correlations between treatment with anticoagulants/antiaggregants and late rectal toxicity after radiotherapy for prostate cancer. Anticancer Res. 2009; 29(5): 1831–1834.
  27. Crivelli JJ, Xylinas E, Kluth LA, et al. Effect of smoking on outcomes of urothelial carcinoma: a systematic review of the literature. Eur Urol. 2014; 65(4): 742–754.
  28. Steinberger E, Kollmeier M, McBride S, et al. Cigarette smoking during external beam radiation therapy for prostate cancer is associated with an increased risk of prostate cancer-specific mortality and treatment-related toxicity. BJU Int. 2015; 116(4): 596–603.
  29. Passarelli MN, Newcomb PA, Hampton JM, et al. Cigarette Smoking Before and After Breast Cancer Diagnosis: Mortality From Breast Cancer and Smoking-Related Diseases. J Clin Oncol. 2016; 34(12): 1315–1322.
  30. Darcey E, Boyle T. Tobacco smoking and survival after a prostate cancer diagnosis: A systematic review and meta-analysis. Cancer Treat Rev. 2018; 70: 30–40.
  31. Bérubé S, Lemieux J, Moore L, et al. Smoking at time of diagnosis and breast cancer-specific survival: new findings and systematic review with meta-analysis. Breast Cancer Res. 2014; 16(2): R42.
  32. Kenfield SA, Stampfer MJ, Chan JM, et al. Smoking and prostate cancer survival and recurrence. JAMA. 2011; 305(24): 2548–2555.

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