|
|
新辅助放疗在直肠癌中的应用及研究进展
|
Abstract:
直肠癌作为最常见的恶性肿瘤之一，近年来发病率及死亡率日益升高。同时，直肠癌的治疗也逐渐标准化，已经有多项研究表明术前同步放化疗联合根治性手术治疗已成为直肠癌的标准治疗方法。全世界也在为提高放化疗疗效和更好的个体化治疗而探索。本文对新辅助放疗中的放疗方案的选择、放射治疗技术、放疗后手术时间间隔、放疗不良反应以及不同放疗技术下危及器官的剂量受量等问题的最新研究进展进行了系统性的综述。以期待未来直肠癌能进行更个性化的治疗。
As one of the most common malignant tumors, the incidence and mortality of rectal cancer have been increasing in recent years. At the same time, the treatment of rectal cancer has been gradually standardized, and a number of studies have shown that preoperative concurrent chemoradiother-apy combined with radical surgery has become the standard treatment of rectal cancer. The world is also exploring ways to improve the efficacy of chemoradiotherapy and better individualized treatment. In this paper, the latest research progress on the selection of radiotherapy scheme in neoadjuvant radiotherapy, radiotherapy technique, surgical interval after radiotherapy, adverse effects of radiotherapy, and dose-receiving of organs at risk under different radiotherapy tech-niques are systematically reviewed, in order to look forward to more personalized treatment of rectal cancer in the future.
| [1] | Siegel, R.L., Miller, K.D. and Jemal, A. (2018) Cancer Statistics, 2018. CA: A Cancer Journal for Clinicians, 68, 7-30.
https://doi.org/10.3322/caac.21442 |
| [2] | 孙可欣, 郑荣寿, 张思维, 等. 2015年中国分地区恶性肿瘤发病和死亡分析[J]. 中国肿瘤, 2019, 28(1): 1-11. |
| [3] | Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A. and Bray, F. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249. https://doi.org/10.3322/caac.21660 |
| [4] | Sauer, R., Becker, H., Hohenberger, W., et al. (2004) Preoperative versus Postoperative Chemoradiotherapy for Rectal Cancer. The New England Journal of Medicine, 351, 1731-1740. https://doi.org/10.1056/NEJMoa040694 |
| [5] | Bosset, J.-F., Collette, L., Calais, G., et al. (2006) Chemotherapy with Preoperative Radiotherapy in Rectal Cancer. The New England Journal of Medicine, 355, 1114-1123. https://doi.org/10.1056/NEJMoa060829 |
| [6] | Sebag-Montefiore, D., Stephens, R.J., Steele, R., et al. (2009) Pre-operative Radiotherapy versus Selective Postoperative Chemoradiotherapy in Patients with Rectal Cancer (MRC CR07 and NCIC-CTG C016): A Multicentre, Randomised Trial. Lancet, 373, 811-820. https://doi.org/10.1016/S0140-6736(09)60484-0 |
| [7] | Glynne-Jones, R., Wyrwicz, L., Tiret, E., et al. (2018) Cor-rections to “Rectal Cancer: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up”. Annals of On-cology, 29, Article No. IV263.
https://doi.org/10.1093/annonc/mdy161 |
| [8] | Couwenberg, A.M., Burbach, J.P.M., Van Grevenstein, W.M.U., et al. (2018) Effect of Neoadjuvant Therapy and Rectal Surgery on Health-Related Quality of Life in Patients with Rectal Cancer during the First 2 Years after Diagnosis. Clinical Colorectal Cancer, 17, e499-e512. https://doi.org/10.1016/j.clcc.2018.03.009 |
| [9] | Roh, M.S., Colangelo, L.H., O’Connell, M.J., Yothers, G., Deutsch, M., Allegra, C.J., Kahlenberg, M.S., Baez-Diaz, L., Ursiny, C.S., Petrelli, N.J. and Wolmark, N. (2009) Preoperative Multimodality Therapy Improves Disease-Free Survival in Patients with Carcinoma of the Rectum: NSABP R-03. Jour-nal of Clinical Oncology, 27, 5124-5130.
https://doi.org/10.1200/JCO.2009.22.0467 |
| [10] | Allegra, C.J., Yothers, G., O’Connell, M.J., Beart, R.W., Wozniak, T.F., Pitot, H.C., Shields, A.F., Landry, J.C., Ryan, D.P., Arora, A., Evans, L.S., Bahary, N., Soori, G., Eakle, J.F., Robertson, J.M., Moore Jr., D.F., Mullane, M.R., Marchello, B.T., Ward, P.J., Sharif, S., Roh, M.S. and Wolmark, N. (2015) Neoadjuvant 5-FU or Capecitabine plus Radiation with or without Oxaliplatin in Rectal Cancer Patients:A Phase III Randomized Clinical Trial. JNCI: Journal of the National Cancer Institute, 107, Article No. djv248. https://doi.org/10.1093/jnci/djv248 |
| [11] | Bujko, K., Nowacki, M.P., K？pka, L., Ol？dzki, J., B？benek, M. and Kryj, M. (2005) Postoperative Complications in Patients Irradiated Pre-Operatively for Rectal Cancer: Report of a Randomised Trial Comparing Short-Term Radiotherapy vs Chemoradiation. Colorectal Disease, 7, 410-416. https://doi.org/10.1111/j.1463-1318.2005.00796.x |
| [12] | Radu, C., Berglund, A., Pahlman, L. and Glimelius, B. (2008) Short-Course Preoperative Radiotherapy with Delayed Surgery in Rectal Cancer—A Retrospective Study. Radio-therapy and Oncology, 87, 343-349.
https://doi.org/10.1016/j.radonc.2007.11.025 |
| [13] | Latkauskas, T., Pauzas, H., Kairevice, L., Petrauskas, A., Saladzinskas, Z., Janciauskiene, R., Gudaityte, J., Lizdenis, P., Svagzdys, S., Tamelis, A. and Pavalkis, D. (2016) Pre-operative Conventional Chemoradiotherapy versus Short-Course Radiotherapy with Delayed Surgery for Rectal Cancer: Results of a Randomized Controlled Trial. BMC Cancer, 16, Article No. 927. https://doi.org/10.1186/s12885-016-2959-9 |
| [14] | Yu, Y., Li, Y., Xu, C., Zhang, Z. and Zhang, X. (2019) Compar-ison of Long Course and Short Course Preoperative Radiotherapy in the Treatment of Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis. Revista Espanola de Enfermedades Digestivas, 111, 17-27. https://doi.org/10.17235/reed.2018.5674/2018 |
| [15] | Simillis, C., Khatri, A., Dai, N., Afxentiou, T., Jephcott, C., Smith, S., Jadon, R., Papamichael, D., Khan, J., Powar, M.P., Fearnhead, N.S., Wheeler, J. and Davies, J. (2023) A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials Comparing Neoadjuvant Treatment Strategies for Stage II and III Rectal Cancer. Critical Reviews in Oncology/Hematology, 183, Article ID: 103927. https://doi.org/10.1016/j.critrevonc.2023.103927 |
| [16] | Alawawdeh, A., Krishnan, T., Roy, A., et al. (2021) Curative Therapy for Rectal Cancer. Expert Review of Anticancer Therapy, 21, 193-203. https://doi.org/10.1080/14737140.2021.1845145 |
| [17] | Glynne-Jones, R., Grainger, J., Harrison, M., Ostler, P. and Makris, A. (2006) Neoadjuvant Chemotherapy Prior to Preoperative Chemoradiation or Radiation in Rectal Cancer: Should We Be More Cautious? British Journal of Cancer, 94, 363-371. https://doi.org/10.1038/sj.bjc.6602960 |
| [18] | Chua, Y.J., Barbachano, Y., Cunningham, D., et al. (2010) Neoadju-vant Capecitabine and Oxaliplatin Before Chemoradiotherapy and Total Mesorectal Excision in MRI-Defined Poor-Risk Rectal Cancer: A Phase 2 Trial. The Lancet Oncology, 11, 241-248. https://doi.org/10.1016/S1470-2045(09)70381-X |
| [19] | Gao, Y.-H., Lin, J.-Z., An, X., et al. (2014) Neoadjuvant Sandwich Treatment with Oxaliplatin and Capecitabine Administered Prior to, Concurrently with, and Following Radia-tion Therapy in Locally Advanced Rectal Cancer: A Prospective Phase 2 Trial. International Journal of Radiation On-cology, Biology, Physics, 90, 1153-1160.
https://doi.org/10.1016/j.ijrobp.2014.07.021 |
| [20] | Azin, A., Khorasani, M. and Quereshy, F.A. (2019) Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer: The Surgeon’s Perspective. Journal of Clinical Pathology, 72, 133-134. https://doi.org/10.1136/jclinpath-2018-205595 |
| [21] | Goodman, K.A. (2018) Total Neoadjuvant Therapy for Rectal Cancer. Cancer/Radiothérapie, 22, 459-465.
https://doi.org/10.1016/j.canrad.2018.01.004 |
| [22] | Kim, H.S. and Kim, N.K. (2020) Challenges and Shifting Treat-ment Strategies in the Surgical Treatment of Locally Advanced Rectal Cancer. Annals of Gastroenterological Surgery, 4, 379-385. https://doi.org/10.1002/ags3.12349 |
| [23] | Gollins, S. and Sebag-Montefiore, D. (2016) Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer. Clinical Oncology, 28, 146-151. https://doi.org/10.1016/j.clon.2015.11.003 |
| [24] | Cercek, A., Roxburgh, C.S.D., Strombom, P., et al. (2018) Adop-tion of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer. JAMA Oncology, 4, e180071. https://doi.org/10.1001/jamaoncol.2018.0071 |
| [25] | Garcia-Aguilar, J., Patil, S., Kim, J., et al. (2020) Preliminary Results of the Organ Preservation of Rectal Adenocarcinoma (Opra) Trial. Journal of Clinical Oncology, 38, Article No. 4008.
https://doi.org/10.1200/JCO.2020.38.15_suppl.4008 |
| [26] | Xiao, W. (2019) TNT versus Conventional CRT to In-crease the Sphincter Preservation Rate for Distal LARC (TESS).
https://www.clinicaltrials.gov/ct2/show/NCT03840239 |
| [27] | Liu, S., Jiang, T., Xiao, L., Yang, S., Liu, Q., Gao, Y., Chen, G. and Xiao, W. (2021) Total Neoadjuvant Therapy (TNT) versus Standard Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis. The Oncologist, 26, e1555-e1566. https://doi.org/10.1002/onco.13824 |
| [28] | Ngan, S.Y., Burmeister, B., Fisher, R.J., et al. (2012) Randomized Trial of Short-Course Radiotherapy versus Long-Course Chemoradiation Comparing Rates of Local Recurrence in Patients with T3 Rectal Cancer: Trans-Tasman Radiation Oncology Group Trial 01.04. Journal of Clinical Oncology, 30, 3827-3833.
https://doi.org/10.1200/JCO.2012.42.9597 |
| [29] | Zhou, Z.-R., Liu, S.-X., Zhang, T.-S., et al. (2014) Short-Course Preoperative Radiotherapy with Immediate Surgery versus Long-Course Chemoradiation with Delayed Surgery in the Treatment of Rectal Cancer: A Systematic Review and Meta-Analysis. Surgical Oncology, 23, 211-221. https://doi.org/10.1016/j.suronc.2014.10.003 |
| [30] | Glimelius, B. (2017) On a Prolonged Interval between Rectal Cancer (Chemo)Radiotherapy and Surgery. Upsala Journal of Medical Sciences, 122, 1-10. https://doi.org/10.1080/03009734.2016.1274806 |
| [31] | de Campos-Lobato, L.F., Geisler, D.P., da Luz Moreira, A., Stocchi, L., Dietz, D. and Kalady, M.F. (2011) Neoadjuvant Therapy for Rectal Cancer: The Impact of Longer Interval between Chemoradiation and Surgery. Journal of Gastrointestinal Surgery, 15, 444-450. https://doi.org/10.1007/s11605-010-1197-8 |
| [32] | Zorcolo, L., Rosman, A.S., Restivo, A., Pisano, M., Nigri, G.R., Fancellu, A., et al. (2012) Complete Pathologic Response after Combined Modality Treatment for Rectal Cancer and Long-Term Survival: A Meta-Analysis. Annals of Surgical Oncology, 19, 2822-2832. https://doi.org/10.1245/s10434-011-2209-y |
| [33] | Francois, Y., Nemoz, C.J., Baulieux, J., et al. (1999) Influence of the Interval between Preoperative Radiation Therapy and Surgery on Downstaging and on the Rate of Sphincter-Sparing Surgery for Rectal Cancer: The Lyon R90-01 Randomized Trial. Journal of Clinical Oncology, 17, 2396-2402. 1 https://doi.org/10.1200/JCO.1999.17.8.2396 |
| [34] | Akgun, E., Caliskan, C., Bozbiyik, O., Yoldas, T., Sezak, M., Ozkok, S., Kose, T., Karabulut, B., Harman, M. and Ozutemiz, O. (2018) Randomized Clinical Trial of Short or Long Interval between Neoadjuvant Chemoradiotherapy and Surgery for Rectal Cancer. British Journal of Surgery, 105, 1417-1425. https://doi.org/10.1002/bjs.10984 |
| [35] | Terzi, C., Bingul, M., Arslan, N.C., Ozturk, E., Canda, A.E., Isik, O., Yilmazlar, T., Obuz, F., Birkay Gorken, I., Kurt, M., Unlu, M., Ugras, N., Kanat, O. and Oztop, I. (2020) Ran-domized Controlled Trial of 8 Weeks’ vs 12 Weeks’ Interval between Neoadjuvant Chemoradiotherapy and Surgery for Locally Advanced Rectal Cancer. Colorectal Disease, 22, 279-288. https://doi.org/10.1111/codi.14867 |
| [36] | Wu, H., Fang, C., Huang, L., Fan, C., Wang, C., Yang, L., Li, Y. and Zhou, Z. (2018) Short-Course Radiotherapy with Immedi-ate or Delayed Surgery in Rectal Cancer: A Meta-Analysis. International Journal of Surgery, 56, 195-202.
https://doi.org/10.1016/j.ijsu.2018.05.031 |
| [37] | Lefèvre, J.H., Mineur, L., Cachanado, M., Denost, Q., Rouanet, P., de Chaisemartin, C., Meunier, B., Mehrdad, J., Cotte, E., Desrame, J., Karoui, M., Benoist, S., Kirzin, S., Berger, A., Panis, Y., Piessen, G., Saudemont, A., Prudhomme, M., Peschaud, F., Dubois, A., Loriau, J., Tuech, J.-J., Meurette, G., Lupinacci, R., Goasguen, N., Creavin, B., Simon, T. and Parc, Y. (2019) Does a Longer Waiting Period after Neoadju-vant Radio-Chemotherapy Improve the Oncological Prognosis of Rectal Cancer?: Three Years’ Follow-Up Results of the Greccar-6 Randomized Multicenter Trial. Annals of Surgery, 270, 747-754. https://doi.org/10.1097/SLA.0000000000003530 |
| [38] | Gwynne, S. and Staffurth, J. (2012) Principles of Cancer Treatment by Radiotherapy. Surgery, 30, 191-193.
https://doi.org/10.1016/j.mpsur.2012.01.012 |
| [39] | Erlandsson, J., Holm, T., Pettersson, D., Berglund, ？., Cedermark, B., Radu, C., Johansson, H., Machado, M., Hjern, F., Hallb？？k, O., Syk, I., Glimelius, B. and Martling, A. (2017) Optimal Fractionation of Preoperative Radiotherapy and Timing to Surgery for Rectal Cancer (Stockholm III): A Multicentre, Randomised, Non-Blinded, Phase 3, Non-Inferiority Trial. The Lancet Oncology, 18, 336-346. https://doi.org/10.1016/S1470-2045(17)30086-4 |
| [40] | Baglan, K.L., Frazier, R.C., Yan, D., Huang, R.R., Martinez, A.A. and Robertson, J.M. (2002) The Dose-Volume Realationship of Acute Small Bowel Toxicity from Concurrent 5-FU-Based Chemotherapy and Radiation Therapy for Rectal Cancer. International Journal of Radiation Oncology, Bi-ology, Physics, 52, 176-183.
https://doi.org/10.1016/S0360-3016(01)01820-X |
| [41] | Tho, L.M., Glegg, M., Paterson, J., Yap, C., MacLeod, A., McCabe, M. and McDonald, A.C. (2006) Acute Small Bowel Toxicity and Preoperative Chemoradiotherapy for Rectal Cancer: Investigating Dose-Volume Relationships and Role for Inverse Planning. International Journal of Radiation Oncology, Biology, Physics, 66, 505-513.
https://doi.org/10.1016/j.ijrobp.2006.05.005 |
| [42] | Robertson, J.M., Lockman, D., Yan, D. and Wallace, M. (2008) The Dose-Volume Relationship of Small Bowel Irradiation and Acute Grade 3 Diarrhea during Chemoradiotherapy for Rectal Cancer. International Journal of Radiation Oncology, Biology, Physics, 70, 413-418. https://doi.org/10.1016/j.ijrobp.2007.06.066 |
| [43] | Wolff, H.A., Wagner, D.M., Conradi, L.C., Hennies, S., Ghadimi, M., Hess, C.F. and Christiansen, H. (2012) Irradiation with Protons for the Individualized Treatment of Patients with Locally Advanced Rectal Cancer: A Planning Study with Clinical Implications. Radiotherapy and Oncology, 102, 30-37. https://doi.org/10.1016/j.radonc.2011.10.018 |
| [44] | Polico, C., Capirci, C., Stevanin, C., et al. (1993) Enteropatia da Raggi. Scientifiche Nutricia, Milano, 1-44. |
| [45] | Harling, H. and Balslev, I. (1988) Long-Term Prognosis of Patients with Severe Radiation Enteritis. The American Journal of Surgery, 155, 517-519. https://doi.org/10.1016/S0002-9610(88)80126-0 |
| [46] | Pointreau, Y., Atean, I. and Durdux, C. (2010) Dose de tolérance à l’irradiation des tissus sains: La vessie [Normal Tissue Tolerance to External Beam Radiation Therapy: Bladder]. Cancer/Radiothérapie, 14, 363-368. (In French)
https://doi.org/10.1016/j.canrad.2010.02.007 |
| [47] | Li, Y., Wang, J., Ma, X., Tan, L., Yan, Y., Xue, C., et al. (2016) A Review of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer. International Journal of Biological Sciences, 12, 1022-1031.
https://doi.org/10.7150/ijbs.15438 |
| [48] | Buchli, C., Martling, A., Arver, S. and Holm, T. (2011) Testicular Function after Radiotherapy for Rectal Cancer—A Review. The Journal of Sexual Medicine, 8, 3220-3226. https://doi.org/10.1111/j.1743-6109.2011.02455.x |
| [49] | De Felice, F., Marchetti, C., Marampon, F., Cascialli, G., Muzii, L. and Tombolini, V. (2019) Radiation Effects on Male Fertility. Andrology, 7, 2-7. https://doi.org/10.1111/andr.12562 |
| [50] | World Health Organization (2010) WHO Laboratory Manual for the Ex-amination and Processing of Human Semen. 5th Edition, World Health Organization, Geneva. https://fctc.who.int/publications/i/item/9789241547789 |
| [51] | Hennies, S., Wolff, H., Jung, K., Rave-Fr？nk, M., Gaedcke, J., Ghadimi, M., et al. (2012) Testicular Radiation Dose after Multimodal Curative Therapy for Locally Ad-vanced Rectal Cancer. Influence on Hormone Levels, Quality of Life, and Sexual Functioning. Strahlentherapie und Onkologie, 188, 926-932.
https://doi.org/10.1007/s00066-012-0139-7 |
| [52] | de la Motte, L., Custovic, S., Tapper, J., Arver, S., Martling, A. and Buchli, C. (2021) Effect of Preoperative Radiotherapy for Rectal Cancer on Spermatogenesis. British Journal of Surgery, 108, 750-753.
https://doi.org/10.1093/bjs/znab019 |
| [53] | Eade, T.N., Hanlon, A.L., Horwitz, E.M., Buyyounouski, M.K., Hanks, G.E. and Pollack, A. (2007) What Dose of External-Beam Radiation Is High Enough for Prostate Cancer? International Journal of Radiation Oncology, Biology, Physics, 68, 682-689. https://doi.org/10.1016/j.ijrobp.2007.01.008 |
| [54] | Viani, G.A., Stefano, E.J. and Afonso, S.L. (2009) High-er-Than-Conventional Radiation Doses in Localized Prostate Cancer Treatment: A Meta-Analysis of Randomized, Con-trolled Trials. International Journal of Radiation Oncology, Biology, Physics, 74, 1405-1418. https://doi.org/10.1016/j.ijrobp.2008.10.091 |
| [55] | Mellon, E.A., Javedan, K., Strom, T.J., Moros, E.G., Biagioli, M.C., Fernandez, D.C., et al. (2015) A Dosimetric Comparison of Volumetric Modulated Arc Therapy with Step-and-Shoot Intensity Modulated Radiation Therapy for Prostate Cancer. Practical Radiation Oncology, 5, 11-15. https://doi.org/10.1016/j.prro.2014.03.003 |
| [56] | Dr？ge, L.H., Weber, H.E., Guhlich, M., Leu, M., Conradi, L.C., Gaedcke, J., et al. (2015) Reduced Toxicity in the Treatment of Locally Advanced Rectal Cancer: A Comparison of Volumetric Modulated Arc Therapy and 3D Conformal Radiotherapy. BMC Cancer, 15, Article No. 750. https://doi.org/10.1186/s12885-015-1812-x |
| [57] | Zhao, J., Hu, W., Cai, G., Wang, J., Xie, J., Peng, J., et al. (2016) Dosimetric Comparisons of VMAT, IMRT and 3DCRT for Locally Advanced Rectal Cancer with Simultaneous Inte-grated Boost. Oncotarget, 7, 6345-6351.
https://doi.org/10.18632/oncotarget.6401 |
| [58] | Shi, J., Yang, F., Ju, X., Huang, Y. and Jiang, F. (2017) Compara-tive Study on Dosimetry of VMAT and IMRT in Assisted Radiotherapy after Radical Resection of Rectal Cancer. On-cology Letters, 13, 2971-2974.
https://doi.org/10.3892/ol.2017.5842 |
| [59] | Duman, E., Bilek, Y. and Ceyran, G. (2021) A Comparison of Radio-therapy Treatment Planning Techniques in Patients with Rectal Cancers by Analyzing Testes Doses. Journal of Cancer Research and Therapeutics, 17, 56-61.
https://doi.org/10.4103/jcrt.JCRT_328_19 |
