Abstract：Second primary cancer (SPC) is one of the main late toxicities of tumor therapy. According to statistics, one out of every 12 cancer survivors will develop SPC, and more than half of the cancer survivors will die of SPC. At present, approximately 70% of cancer patients receive radiotherapy (RT) throughout the course of disease. Whether high‐dose radiation will increase the risk of SPC has captivated widespread attention. Among them, most pelvic tumor patients should receive RT because of the high incidence. In this article, relevant studies of potential pathogenesis of SPC, impact of different RT techniques, selection of RT timing, and RT for male, female and pediatric pelvic tumors were reviewed, aiming to investigate whether pelvic RT will increase the risk of SPC.
Huang Yan,Lu Chunhua,Zhang Ying et al. Whether radiotherapy for pelvic tumor increases the risk of second primary cancer[J]. Chinese Journal of Radiation Oncology, 2022, 31(8): 745-749.
[1] Donin N, Filson C, Drakaki A, et al.Risk of second primary malignancies among cancer survivors in the United States, 1992 through 2008[J]. Cancer, 2016,122(19):3075‐3086.DOI: 10.1002/cncr.30164. [2] Shuryak I, Sachs RK, Brenner DJ.Cancer risks after radiation exposure in middle age[J]. J Natl Cancer Inst, 2010,102(21):1628‐1636.DOI: 10.1093/jnci/djq346. [3] Hernández L, Terradas M, Camps J, et al.Aging and radiation: bad companions[J]. Aging Cell, 2015,14(2):153‐161.DOI: 10.1111/acel.12306. [4] Krasnow RE, Rodríguez D, Nagle RT, et al.The impact of age at the time of radiotherapy for localized prostate cancer on the development of second primary malignancies[J]. Urol Oncol, 2018,36(11):500.e11‐500.e19.DOI: 10.1016/j.urolonc.2018.06.007. [5] Journy N, Mansouri I, Allodji RS, et al.Volume effects of radiotherapy on the risk of second primary cancers: A systematic review of clinical and epidemiological studies[J]. Radiother Oncol, 2019,131:150‐159.DOI: 10.1016/j.radonc.2018.09.017. [6] Journy NM, Morton LM, Kleinerman RA, et al.Second primary cancers after intensity‐modulated vs 3‐dimensional conformal radiation therapy for prostate cancer[J]. JAMA Oncol, 2016,2(10):1368‐1370.DOI: 10.1001/jamaoncol.2016.1368. [7] Chung CS, Yock TI, Nelson K, et al.Incidence of second malignancies among patients treated with proton versus photon radiation[J]. Int J Radiat Oncol Biol Phys, 2013,87(1):46‐52.DOI: 10.1016/j.ijrobp.2013.04.030. [8] Zwahlen DR, Ruben JD, Jones P, et al.Effect of intensity‐modulated pelvic radiotherapy on second cancer risk in the postoperative treatment of endometrial and cervical cancer[J]. Int J Radiat Oncol Biol Phys, 2009,74(2):539‐545.DOI: 10.1016/j.ijrobp.2009.01.051. [9] Chargari C, Goodman KA, Diallo I, et al.Risk of second cancers in the era of modern radiation therapy: does the risk/benefit analysis overcome theoretical models?[J]. Cancer Metastasis Rev, 2016,35(2):277‐288.DOI: 10.1007/s10555‐016‐9616‐2. [10] Murray LJ, Thompson CM, Lilley J, 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) andflattening filter free (FFF) radiotherapy[J]. Phys Med Biol, 2015,60(3):1237‐1257.DOI: 10.1088/0031‐9155/60/3/1237. [11] Stokkevåg CH, Engeseth GM, Hysing LB, et al.The influence of inter‐fractional anatomy variation on secondary cancer risk estimates following radiotherapy[J]. Phys Med, 2017,42:271‐276.DOI: 10.1016/j.ejmp.2017.09.125. [12] Smith‐Gagen J, Goodwin GA, Tay J.Multiple primary tumors following stage II and III rectal cancer in patients receiving radiotherapy, 1998‐2010[J]. J Cancer Res Clin Oncol, 2014,140(6):949‐955.DOI: 10.1007/s00432‐014‐1647‐x. [13] Sauer R, Becker H, Hohenberger W, et al.Preoperative versus postoperative chemoradiotherapy for rectal cancer[J]. N Engl J Med, 2004,351(17):1731‐1740.DOI: 10.1056/NEJMoa040694. [14] Moschini M, Zaffuto E, Karakiewicz PI, et al.External beam radiotherapy increases the risk of bladder cancer when compared with radical prostatectomy in patients affected by prostate cancer: a population‐based analysis[J]. Eur Urol, 2019,75(2):319‐328.DOI: 10.1016/j.eururo.2018.09.034. [15] Moschini M, Zaffuto E, Mattei A, et al.Reply to Alba Fiorentino, Angelo Errico, and Marcello Scarcia's Letter to the Editor re: Marco Moschini, Emanuele Zaffuto, Pierre I.Karakiewicz,et al.external beam radiotherapy increases the risk of bladder cancer when compared with radical prostatectomy in patients affected by prostate cancer: a population‐based analysis.Eur Urol 2019;75:319‐28: radiation therapy versus radical prostatectomy: no way out without a randomized trial.Eur Urol.2019, 75(4):e95.DOI: 10.1016/j.eururo.2018.11.043. [16] Zaorsky NG, Spratt DE, Blanchard P.Re: Marco Moschini, Emanuele Zaffuto, Pierre I.Karakiewicz,et al.external beam radiotherapy increases the risk of bladder cancer when compared with radical prostatectomy in patients affected by prostate cancer: a population‐based analysis.Eur Urol2019;75:319‐28[J]. Eur Urol, 2019,75(4):e96‐e97.DOI: 10.1016/j.eururo.2018.11.025. [17] Aksnessæther BY, Myklebust TÅ, Solberg A, et al.Second cancers in patients with locally advanced prostate cancer randomized to lifelong endocrine treatment with or without radical radiation therapy: long‐term follow‐up of the Scandinavian Prostate Cancer Group‐7 Trial[J]. Int J Radiat Oncol Biol Phys, 2020,106(4):706‐714.DOI: 10.1016/j.ijrobp.2019.11.027. [18] Wallis CJ, Mahar AL, Choo R, et al.Second malignancies after radiotherapy for prostate cancer: systematic review and meta‐analysis[J]. BMJ, 2016,352:i851.DOI: 10.1136/bmj.i851. [19] Warschkow R, Güller U, Cerny T, et al.Secondary malignancies after rectal cancer resection with and without radiation therapy: A propensity‐adjusted, population‐based SEER analysis[J]. Radiother Oncol, 2017,123(1):139‐146.DOI: 10.1016/j.radonc.2017.02.007. [20] Koivisto‐Korander R, Scélo G, Ferro G, et al.Second primary malignancies among women with uterine sarcoma[J]. Gynecol Oncol, 2012,126(1):30‐35.DOI: 10.1016/j.ygyno.2012.04.002. [21] Wiltink LM, Nout RA, Fiocco M, et al.No increased risk of second cancer after radiotherapy in patients treated for rectal or endometrial cancer in the randomized TME, PORTEC‐1,PORTEC‐2 Trials[J]. J Clin Oncol, 2015,33(15):1640‐1646.DOI: 10.1200/JCO.2014.58.6693. [22] Wissing MD, Azoulay L.Postoperative pelvic radiotherapy in patients with endometrial cancer may increase the risk for secondary pelvic cancers: a post hoc analysis of results from the TME, PORTEC‐1,PORTEC‐2 Trials[J]. J Clin Oncol, 2017,35(16):1861‐1862.DOI: 10.1200/JCO.2017.72.6497. [23] Arnold M, Liu L, Kenter GG, et al.Second primary cancers in survivors of cervical cancer in the Netherlands: implications for prevention and surveillance[J]. Radiother Oncol, 2014,111(3):374‐381.DOI: 10.1016/j.radonc.2014.04.011. [24] Chaturvedi AK, Engels EA, Gilbert ES, et al.Second cancers among 104,760 survivors of cervical cancer: evaluation of long‐term risk[J]. J Natl Cancer Inst, 2007,99(21):1634‐1643.DOI: 10.1093/jnci/djm201. [25] Wright JD, St Clair CM, Deutsch I, et al.Pelvic radiotherapy and the risk of secondary leukemia and multiple myeloma[J]. Cancer, 2010,116(10):2486‐2492.DOI: 10.1002/cncr.25067. [26] Matsuo K, Blake EA, Machida H, et al.Incidences and risk factors of metachronous vulvar, vaginal,anal cancers after cervical cancer diagnosis[J]. Gynecol Oncol, 2018,150(3):501‐508.DOI: 10.1016/j.ygyno.2018.07.016. [27] Papatla K, Houck KL, Hernandez E, et al.Second primary uterine malignancies after radiation therapy for cervical cancer[J]. Arch Gynecol Obstet, 2019,300(2):389‐394.DOI: 10.1007/s00404‐019‐05187‐9. [28] Rombouts A, Hugen N, Elferink M, et al.Incidence of second tumors after treatment with or without radiation for rectal cancer[J]. Ann Oncol, 2017,28(3):535‐540.DOI: 10.1093/annonc/mdw661. [29] Kendal WS, Nicholas G.A population‐based analysis of second primary cancers after irradiation for rectal cancer[J]. Am J Clin Oncol, 2007,30(4):333‐339.DOI: 10.1097/01.coc.0000258084.55036.9e. [30] Rombouts A, Hugen N, van Beek J, et al.Does pelvic radiation increase rectal cancer incidence?‐ A systematic review and meta‐analysis[J]. Cancer Treat Rev, 2018,68:136‐144.DOI: 10.1016/j.ctrv.2018.05.008. [31] Martling A, Smedby KE, Birgisson H, et al.Risk of second primary cancer in patients treated with radiotherapy for rectal cancer[J]. Br J Surg, 2017,104(3):278‐287.DOI: 10.1002/bjs.10327. [32] Schneider U, Besserer J, Mack A.Hypofractionated radiotherapy has the potential for second cancer reduction[J]. Theor Biol Med Model, 2010,7:4.DOI: 10.1186/1742‐4682‐7‐4. [33] Buchli C, Martling A, Arver S, et al.Testicular function after radiotherapy for rectal cancer‐‐a review[J]. J Sex Med, 2011,8(11):3220‐3226.DOI: 10.1111/j.1743‐6109.2011.02455.x. [34] Hird AE, Magee DE, Matta R, et al.Assessment of secondary sarcomas among patients with cancer of the abdomen or pelvis who received combinations of surgery, radiation, and chemotherapy vs surgery alone[J]. JAMA Netw Open, 2020,3(10):e2013929.DOI: 10.1001/jamanetworkopen.2020.13929. [35] Meadows AT, Friedman DL, Neglia JP, et al.Second neoplasms in survivors of childhood cancer: findings from the Childhood Cancer Survivor Study cohort[J]. J Clin Oncol, 2009,27(14):2356‐2362.DOI: 10.1200/JCO.2008.21.1920. [36] Henderson TO, Oeffinger KC, Whitton J, et al.Secondary gastrointestinal cancer in childhood cancer survivors: a cohort study[J]. Ann Intern Med, 2012,156(11):757‐766, W‐260.DOI: 10.7326/0003‐4819‐156‐11‐201206050‐00002. [37] Nottage K, McFarlane J, Krasin MJ, et al.Secondary colorectal carcinoma after childhood cancer[J]. J Clin Oncol, 2012,30(20):2552‐2558.DOI: 10.1200/JCO.2011.37.8760. [38] Reulen RC, Frobisher C, Winter DL, et al.Long‐term risks of subsequent primary neoplasms among survivors of childhood cancer[J]. JAMA, 2011,305(22):2311‐2319.DOI: 10.1001/jama.2011.747. [39] Rübe CE, Fricke A, Schneider R, et al.DNA repair alterations in children with pediatric malignancies: novel opportunities to identify patients at risk for high‐grade toxicities[J]. Int J Radiat Oncol Biol Phys, 2010,78(2):359‐369.DOI: 10.1016/j.ijrobp.2009.08.052. [40] Morton LM, Karyadi DM, Hartley SW, et al.Subsequent neoplasm risk associated with rare variants in DNA damage response and clinical radiation sensitivity syndrome genes in the childhood cancer survivor study[J]. JCO Precis Oncol, 2020,4.DOI: 10.1200/PO.20.00141.
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