Estimation of second cancer risk after radiotherapy for rectal cancer: comparison of 3D conformal radiotherapy and volumetric modulated arc therapy using different high dose fractionation schemes

Daniel R Zwahlen, Laura I Bischoff, Günther Gruber, Marcin Sumila, Uwe Schneider, Daniel R Zwahlen, Laura I Bischoff, Günther Gruber, Marcin Sumila, Uwe Schneider

Abstract

Purpose: To investigate second cancer risk (SCR) comparing volumetric modulated arc therapy (VMAT) and 3D conformal radiotherapy (3DCRT) with different high dose fractionation schemes.

Methods: VMAT and 3DCRT virtual treatment plans for 25 patients previously treated with radiotherapy for rectal cancer were evaluated retrospectively. Doses prescribed were 25 × 1.8 Gy and 5 × 5 Gy, respectively. SCR was estimated using a carcinogenesis model and epidemiological data for carcinoma and sarcoma induction. SCR was determined by lifetime attributable risk (LAR).

Results: Mean excess LAR was highest for organs adjacent to the PTV. Total LAR for VMAT and 3DCRT was 2.3-3.0 and 2.0-2.7 %, respectively. For 5 × 5 Gy, LAR was 1.4-1.9 % for VMAT and 1.2-1.6 % for 3DCRT. Organ-specific excess LAR was significantly higher for VMAT, and highest for bladder and colon. Size and shape of the PTV influenced SCR and was highest for age ≤ 40 years. For a patient with an additional lifetime risk of 60 years, LAR was 10 % for 25 × 1.8 Gy and 6 % for 5 × 5 Gy.

Conclusions: No statistically significant difference was detected in SCR using VMAT or 3DCRT. For bladder and colon, organ-specific excess LAR was statistically lower using 3DCRT, however the difference was small. Compared to epidemiological data, SCR was smaller when using a hypofractionated schedule. SCR was 2 % higher at normal life expectancy.

Trial registration: ClinicalTrials.gov Identifier NCT02572362 . Registered 4 October 2015. Retrospectively registered.

Keywords: Intensity-modulated radiotherapy; Radiotherapy; Rectal cancer; Second malignancies; Volumetric-modulated arc therapy.

Figures

Fig. 1
Fig. 1
LAR for each patient with RT 25 × 1.8 Gy, R = 1
Fig. 2
Fig. 2
LAR for each patient with 5 × 5 Gy, R = 1
Fig. 3
Fig. 3
LAR with a variable age at exposure and attained age of 90 years for RT 25 × 1.8 Gy
Fig. 4
Fig. 4
LAR with a variable age at exposure and attained age of 90 years for 5 × 5 Gy
Fig. 5
Fig. 5
LAR for the patients treated with 30 × 2 Gy and 5 × 5 Gy (Uppsala Trial) [4, 20] as well as 25 × 1.8 Gy and 5 × 5y (S-model) [17] over 20 years (age 69 – 89) and no RT

References

    1. Tubiana M. Can we reduce the incidence of second primary malignancies occurring after radiotherapy? A critical review. Radiother Oncol. 2009;91(1):4–15. doi: 10.1016/j.radonc.2008.12.016.
    1. Frykholm GJ, Glimelius B, Pahlman L. Preoperative or postoperative irradiation in adenocarcinoma of the rectum: final treatment results of a randomized trial and an evaluation of late secondary effects. Dis Colon Rectum. 1993;36(6):564–72. doi: 10.1007/BF02049863.
    1. Trial SRC. Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial. N Engl J Med. 1997;336(14):980–7. doi: 10.1056/NEJM199704033361402.
    1. Birgisson H, et al. Occurrence of second cancers in patients treated with radiotherapy for rectal cancer. J Clin Oncol. 2005;23(25):6126–31. doi: 10.1200/JCO.2005.02.543.
    1. Wiltink LM, et al. No increased risk of second cancer after radiotherapy in patients treated for rectal or endometrial cancer in the randomized TME, PORTEC-1, and PORTEC-2 trials. J Clin Oncol. 2015;33(15):1640–6. doi: 10.1200/JCO.2014.58.6693.
    1. Kendal WS, Nicholas G. A population-based analysis of second primary cancers after irradiation for rectal cancer. Am J Clin Oncol. 2007;30(4):333–9. doi: 10.1097/01.coc.0000258084.55036.9e.
    1. Sauer R, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30(16):1926–33. doi: 10.1200/JCO.2011.40.1836.
    1. Glimelius B, et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24 Suppl 6:vi81–8.
    1. van Gijn W, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 2011;12(6):575–82. doi: 10.1016/S1470-2045(11)70097-3.
    1. Morton LM et al. The rising incidence of second cancers: patterns of occurrence and identification of risk factors for children and adults. Am Soc Clin Oncol Educ Book. 2014:e57-67. doi:10.14694/EdBook_AM.2014.34.e57.
    1. Sachs RK, Brenner DJ. Solid tumor risks after high doses of ionizing radiation. Proc Natl Acad Sci U S A. 2005;102(37):13040–5. doi: 10.1073/pnas.0506648102.
    1. Kellerer AM, Nekolla EA, Walsh L. On the conversion of solid cancer excess relative risk into lifetime attributable risk. Radiat Environ Biophys. 2001;40(4):249–57. doi: 10.1007/s004110100106.
    1. 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 radiotherapy. Theor Biol Med Model. 2011;8:27. doi: 10.1186/1742-4682-8-27.
    1. Schneider U, et al. Estimation of radiation-induced cancer from three-dimensional dose distributions: concept of organ equivalent dose. Int J Radiat Oncol Biol Phys. 2005;61(5):1510–5. doi: 10.1016/j.ijrobp.2004.12.040.
    1. Myerson RJ, et al. Elective clinical target volumes for conformal therapy in anorectal cancer: a radiation therapy oncology group consensus panel contouring atlas. Int J Radiat Oncol Biol Phys. 2009;74(3):824–30. doi: 10.1016/j.ijrobp.2008.08.070.
    1. Protection, I.C.o.R The 2007 recommendations of the international commission on radiological protection. ICRP publication 103. Ann ICRP. 2007;37(2-4):1–332. doi: 10.1016/j.icrp.2007.11.001.
    1. Schneider U. Mechanistic model of radiation-induced cancer after fractionated radiotherapy using the linear-quadratic formula. Med Phys. 2009;36(4):1138–43. doi: 10.1118/1.3089792.
    1. Schneider U, Kaser-Hotz B. Radiation risk estimates after radiotherapy: application of the organ equivalent dose concept to plateau dose-response relationships. Radiat Environ Biophys. 2005;44(3):235–9. doi: 10.1007/s00411-005-0016-1.
    1. Preston DL, et al. Solid cancer incidence in atomic bomb survivors: 1958–1998. Radiat Res. 2007;168(1):1–64. doi: 10.1667/RR0763.1.
    1. Pahlman L, Glimelius B, Graffman S. Pre- versus postoperative radiotherapy in rectal carcinoma: an interim report from a randomized multicentre trial. Br J Surg. 1985;72(12):961–6. doi: 10.1002/bjs.1800721209.
    1. Mok H, et al. Intensity modulated radiation therapy (IMRT): differences in target volumes and improvement in clinically relevant doses to small bowel in rectal carcinoma. Radiat Oncol. 2011;6:63. doi: 10.1186/1748-717X-6-63.
    1. Richetti A, et al. Neo-adjuvant chemo-radiation of rectal cancer with volumetric modulated arc therapy: summary of technical and dosimetric features and early clinical experience. Radiat Oncol. 2010;5:14. doi: 10.1186/1748-717X-5-14.
    1. Kjaer-Kristoffersen F, et al. RapidArc volumetric modulated therapy planning for prostate cancer patients. Acta Oncol. 2009;48(2):227–32. doi: 10.1080/02841860802266748.
    1. Rechner LA, et al. Risk of radiogenic second cancers following volumetric modulated arc therapy and proton arc therapy for prostate cancer. Phys Med Biol. 2012;57(21):7117–32. doi: 10.1088/0031-9155/57/21/7117.
    1. Hall EJ, Wuu CS. Radiation-induced second cancers: the impact of 3D-CRT and IMRT. Int J Radiat Oncol Biol Phys. 2003;56(1):83–8. doi: 10.1016/S0360-3016(03)00073-7.
    1. Lillicrap SC, Morgan HM, Shakeshaft JT. X-ray leakage during radiotherapy. Br J Radiol. 2000;73(871):793–4. doi: 10.1259/bjr.73.871.11089476.
    1. Pasler M, Wirtz H, Lutterbach J. Impact of gantry rotation time on plan quality and dosimetric verification--volumetric modulated arc therapy (VMAT) vs. intensity modulated radiotherapy (IMRT) Strahlenther Onkol. 2011;187(12):812–9. doi: 10.1007/s00066-011-2263-1.
    1. Rehman J, et al. Evaluations of secondary cancer risk in spine radiotherapy using 3DCRT, IMRT, and VMAT: A phantom study. Med Dosim. 2015;40(1):70–5. doi: 10.1016/j.meddos.2014.10.003.
    1. Boice JD, Jr, et al. Second cancers following radiation treatment for cervical cancer. An international collaboration among cancer registries. J Natl Cancer Inst. 1985;74(5):955–75.
    1. Dorr W, Herrmann T. Second primary tumors after radiotherapy for malignancies. Treatment-related parameters. Strahlenther Onkol. 2002;178(7):357–62. doi: 10.1007/s00066-002-0951-6.
    1. Hall EJ. Intensity-modulated radiation therapy, protons, and the risk of second cancers. Int J Radiat Oncol Biol Phys. 2006;65(1):1–7. doi: 10.1016/j.ijrobp.2006.01.027.
    1. Howell RM, et al. Calculation of effective dose from measurements of secondary neutron spectra and scattered photon dose from dynamic MLC IMRT for 6 MV, 15 MV, and 18 MV beam energies. Med Phys. 2006;33(2):360–8. doi: 10.1118/1.2140119.
    1. Sachs RK, et al. Second cancers after fractionated radiotherapy: stochastic population dynamics effects. J Theor Biol. 2007;249(3):518–31. doi: 10.1016/j.jtbi.2007.07.034.
    1. Manem VS, et al. Efficacy of dose escalation on TCP, recurrence and second cancer risks: a mathematical study. Br J Radiol. 2014;87(1043):20140377. doi: 10.1259/bjr.20140377.
    1. Schneider U, Besserer J, Mack A. Hypofractionated radiotherapy has the potential for second cancer reduction. Theor Biol Med Model. 2010;7:4. doi: 10.1186/1742-4682-7-4.
    1. Edmondson EF, et al. Tumor Induction in Mice After Localized Single- or Fractionated-Dose Irradiation: Differences in Tumor Histotype and Genetic Susceptibility Based on Dose Scheduling. Int J Radiat Oncol Biol Phys. 2015;92(4):829–36. doi: 10.1016/j.ijrobp.2015.03.002.
    1. Schneider U, Schafer B. Model of accelerated carcinogenesis based on proliferative stress and inflammation for doses relevant to radiotherapy. Radiat Environ Biophys. 2012;51(4):451–6. doi: 10.1007/s00411-012-0433-x.
    1. Hodgson DC, et al. Individualized estimates of second cancer risks after contemporary radiation therapy for Hodgkin lymphoma. Cancer. 2007;110(11):2576–86. doi: 10.1002/cncr.23081.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj