Research progress on chemotherapy for clinical stage Ⅱ nasopharyngeal carcinoma in the era of intensity‐modulated radiotherapy
Liu Yang, Zhang Ye, Yi Junlin
Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Abstract:The prognosis of patients with clinical stage Ⅱ nasopharyngeal carcinoma has been significantly improved by the application of intensity‐modulated radiotherapy (IMRT). Although the NCCN guidelines recommend concurrent chemoradiotherapy strategies for clinical stage Ⅱ nasopharyngeal carcinoma, the evidence is mostly based on the research results under the condition of two‐dimensional conventional radiotherapy, and whether combined chemotherapy is required under the condition of IMRT faces challenges. In this article, current research progress on chemotherapy for clinical phase Ⅱ nasopharyngeal carcinoma was reviewed. Several studies have shown that concurrent, adjuvant and induction chemotherapy failed to improve the efficacy but significantly increased the incidence of toxic and side effects. Because of the heterogeneity in clinical stage Ⅱ nasopharyngeal carcinoma, some studies have found that high‐risk patients could benefit from chemotherapy. Currently, how to distinguish high‐risk patients in clinical stage Ⅱ nasopharyngeal carcinoma is a hot spot. The characteristics of metastatic lymph nodes, EB virus DNA, inflammatory markers, and other factors have certain reference value for screening high‐risk patients, which needs further verification. The prediction model integrating multiple tumor characteristics seems to better identify high‐risk groups and guide the treatment decision of high‐risk stage Ⅱ nasopharyngeal carcinoma.
Liu Yang,Zhang Ye,Yi Junlin. Research progress on chemotherapy for clinical stage Ⅱ nasopharyngeal carcinoma in the era of intensity‐modulated radiotherapy[J]. Chinese Journal of Radiation Oncology, 2022, 31(8): 732-736.
[1] Pfister DG, Spencer S, Adelstein D, et al.Head and Neck Cancers, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology[J]. J Natl Compr Canc Netw, 2020,18(7):873‐898.DOI: 10.6004/jnccn.2020.0031. [2] Chen QY, Wen YF, Guo L, et al.Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial[J]. J Natl Cancer Inst, 2011,103(23):1761‐1770.DOI: 10.1093/jnci/djr432. [3] Kang MK, Oh D, Cho KH, et al.Role of chemotherapy in stage II nasopharyngeal carcinoma treated with curative radiotherapy[J]. Cancer Res Treat, 2015,47(4):871‐878.DOI: 10.4143/crt.2014.141. [4] Su Z, Mao YP, Tang J, et al.Long‐term outcomes of concurrent chemoradiotherapy versus radiotherapy alone in stage II nasopharyngeal carcinoma treated with IMRT: a retrospective study[J]. Tumour Biol, 2016,37(4):4429‐4438.DOI: 10.1007/s13277‐015‐4266‐5. [5] Pan XB, Huang ST, Chen KH, et al.Concurrent chemoradiotherapy degrades the quality of life of patients with stage II nasopharyngeal carcinoma as compared to radiotherapy[J]. Oncotarget, 2017,8(8):14029‐14038.DOI: 10.18632/oncotarget.14932. [6] Liu F, Jin T, Liu L, et al.The role of concurrent chemotherapy for stage II nasopharyngeal carcinoma in the intensity‐modulated radiotherapy era: a systematic review and meta‐analysis[J]. PLoS One, 2018,13(3):e0194733.DOI: 10.1371/journal.pone.0194733. [7] Liu DH, Zhou XY, Pan YG, et al.Survival of stage II nasopharyngeal carcinoma patients with or without concurrent chemotherapy: a propensity score matching study[J]. Cancer Med, 2020,9(4):1287‐1297.DOI: 10.1002/cam4.2785. [8] Su SF, Han F, Zhao C, et al.Long‐term outcomes of early‐stage nasopharyngeal carcinoma patients treated with intensity‐modulated radiotherapy alone[J]. Int J Radiat Oncol Biol Phys, 2012,82(1):327‐333.DOI: 10.1016/j.ijrobp.2010.09.011. [9] Xu T, Hu C, Wang X, et al.Role of chemoradiotherapy in intermediate prognosis nasopharyngeal carcinoma[J]. Oral Oncol, 2011,47(5):408‐413.DOI: 10.1016/j.oraloncology.2011.03.008. [10] Sun XS, Li XY, Xiao BB, et al.Establishment and validation of a nomogram for predicting the benefit of concurrent chemotherapy in stage II nasopharyngeal carcinoma: a study based on a phase III randomized clinical trial with 10‐year follow‐up[J]. Oral Oncol, 2020,100:104490.DOI: 10.1016/j.oraloncology.2019.104490. [11] Luo S, Zhao L, Wang J, et al.Clinical outcomes for early‐stage nasopharyngeal carcinoma with predominantly WHO II histology treated by intensity‐modulated radiation therapy with or without chemotherapy in nonendemic region of China[J]. Head Neck, 2014,36(6):841‐847.DOI: 10.1002/hed.23386. [12] Xu C, Zhang LH, Chen YP, et al.Chemoradiotherapy versus radiotherapy alone in stage II nasopharyngeal carcinoma: a systemic review and meta‐analysis of2138 patients[J]. J Cancer, 2017,8(2):287‐297.DOI: 10.7150/jca.17317. [13] Huang X, Chen X, Zhao C, et al.Adding concurrent chemotherapy to intensity‐modulated radiotherapy does not improve treatment outcomes for stage II nasopharyngeal carcinoma: a phase 2 multicenter clinical trial[J]. Front Oncol, 2020,10:1314.DOI: 10.3389/fonc.2020.01314. [14] Chen KH, Zhu XD, Li L, et al.Comparison of the efficacy between concurrent chemoradiotherapy with or without adjuvant chemotherapy and intensity‐modulated radiotherapy alone for stage II nasopharyngeal carcinoma[J]. Oncotarget, 2016,7(42):69041‐69050.DOI: 10.18632/oncotarget.11978. [15] CHEN S, MENG Y, SHEN Y, et al.Chemotherapy may not be necessary in stage II nasopharyngeal carcinoma treated with intensity‐modulated radiation therapy[J]. Int J Radiat Oncol Biol Phys, 2018, 102(3): S125‐S126.DOI: 10.1016/j.ijrobp.2018.06.313. [16] Wu JS, Tsai YC, Jian JJ, et al.Survival without adjuvant chemotherapy for selected patients with stage II and III nasopharyngeal carcinoma after concurrent chemoradiotherapy alone[J]. Head Neck, 2018,40(9):2070‐2077.DOI: 10.1002/hed.25205. [17] Chen J, Liu T, Sun Q, et al.Comparison of the efficacy between concurrent chemoradiotherapy with or without adjuvant chemotherapy for stage II nasopharyngeal carcinoma[J]. Medicine (Baltimore), 2020,99(29):e20443.DOI: 10.1097/MD.0000000000020443. [18] Wang FZ, Jiang CE, Sun QQ, et al.Addition of chemotherapy to intensity‐modulated radiotherapy does not improve survival in stage II nasopharyngeal carcinoma patients[J]. J Cancer, 2018,9(11):2030‐2037.DOI: 10.7150/jca.25042. [19] Li PJ, Mo HY, Luo DH, et al.The efficacy of induction chemotherapy in the treatment of stage II nasopharyngeal carcinoma in intensity modulated radiotherapy era[J]. Oral Oncol, 2018,85:95‐100.DOI: 10.1016/j.oraloncology.2018.08.016. [20] Jin T, Zhang Q, Luo DH, et al.Concurrent chemoradiotherapy with or without induction chemotherapy for patients with stage II nasopharyngeal carcinoma: an update[J]. Transl Oncol, 2020,13(1):25‐31.DOI: 10.1016/j.tranon.2019.08.007. [21] Kim TH, Ko YH, Lee MA, et al.Treatment outcome of cisplatin‐based concurrent chemoradiotherapy in the patients with locally advanced nasopharyngeal cancer[J]. Cancer Res Treat, 2008,40(2):62‐70.DOI: 10.4143/crt.2008.40.2.62. [22] Tao CJ, Lin L, Zhou GQ, et al.Comparison of long‐term survival and toxicity of cisplatin delivered weekly versus every three weeks concurrently with intensity‐modulated radiotherapy in nasopharyngeal carcinoma[J]. PLoS One, 2014,9(10):e110765.DOI: 10.1371/journal.pone.0110765. [23] Loong HH, Ma BB, Leung SF, et al.Prognostic significance of the total dose of cisplatin administered during concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma[J]. Radiother Oncol, 2012,104(3):300‐304.DOI: 10.1016/j.radonc.2011.12.022. [24] Tang LQ, Chen DP, Guo L, et al.Concurrent chemoradiotherapy with nedaplatin versus cisplatin in stage II‐IVB nasopharyngeal carcinoma: an open‐label, non‐inferiority, randomised phase 3 trial[J]. Lancet Oncol, 2018,19(4):461‐473.DOI: 10.1016/S1470‐2045(18)30104‐9. [25] Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, et al.Chemoradiation comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non‐inferiority, open trial[J]. Eur J Cancer, 2007,43(9):1399‐1406.DOI: 10.1016/j.ejca.2007.03.022. [26] Wu X, Huang PY, Peng PJ, et al.Long‐term follow‐up of a phase III study comparing radiotherapy with or without weekly oxaliplatin for locoregionally advanced nasopharyngeal carcinoma[J]. Ann Oncol, 2013,24(8):2131‐2136.DOI: 10.1093/annonc/mdt163. [27] Liu Y, Chen S, Dong A, et al.Nodal grouping in nasopharyngeal carcinoma: prognostic significance, N classification, and a marker for the identification of candidates for induction chemotherapy[J]. Eur Radiol, 2020,30(4):2115‐2124.DOI: 10.1007/s00330‐019‐06537‐6. [28] Sun XS, Chen WH, Liu SL, et al.Individualized concurrent chemotherapy by pretreatment plasma Epstein‐Barr viral DNA in II‐III stage nasopharyngeal carcinoma: a propensity score matching analysis using a large cohort[J]. Cancer Med, 2019,8(9):4214‐4225.DOI: 10.1002/cam4.2343. [29] He SS, Wang CT, Peng ZW, et al.Development and external validation of a nomogram for predicting the overall survival of patients with stage II nasopharyngeal carcinoma after curative treatment[J]. Cancer Manag Res, 2019,11:4403‐4412.DOI: 10.2147/CMAR.S202151. [30] Xiao WW, Han F, Lu TX, et al.Treatment outcomes after radiotherapy alone for patients with early‐stage nasopharyngeal carcinoma[J]. Int J Radiat Oncol Biol Phys, 2009,74(4):1070‐1076.DOI: 10.1016/j.ijrobp.2008.09.008. [31] Ma H, Liang S, Cui C, et al.Prognostic significance of quantitative metastatic lymph node burden on magnetic resonance imaging in nasopharyngeal carcinoma: a retrospective study of1224 patients from two centers[J]. Radiother Oncol, 2020,151:40‐46.DOI: 10.1016/j.radonc.2020.07.023. [32] Huang CL, Chen Y, Guo R, et al.Prognostic value of MRI‐determined cervical lymph node size in nasopharyngeal carcinoma[J]. Cancer Med, 2020,9(19):7100‐7106.DOI: 10.1002/cam4.3392. [33] Du YY, Luo DH, Sun XS, et al.Combining pretreatment plasma Epstein‐Barr virus DNA level and cervical node necrosis improves prognostic stratification in patients with nasopharyngeal carcinoma: a cohort study[J]. Cancer Med, 2019,8(16):6841‐6852.DOI: 10.1002/cam4.2481. [34] Hu Y, Lu T, Huang SH, et al.High‐grade radiologic extra‐nodal extension predicts distant metastasis in stage II nasopharyngeal carcinoma[J]. Head Neck, 2019,41(9):3317‐3327.DOI: 10.1002/hed.25842. [35] Chen C, Fei Z, Pan J, et al.Significance of primary tumor volume and T‐stage on prognosis in nasopharyngeal carcinoma treated with intensity‐modulated radiation therapy[J]. Jpn J Clin Oncol, 2011,41(4):537‐542.DOI: 10.1093/jjco/hyq242. [36] Sze WM, Lee AW, Yau TK, et al.Primary tumor volume of nasopharyngeal carcinoma: prognostic significance for local control[J]. Int J Radiat Oncol Biol Phys, 2004,59(1):21‐27.DOI: 10.1016/j.ijrobp.2003.10.027. [37] Kim KY, Le QT, Yom SS, et al.Clinical utility of Epstein‐Barr virus DNA testing in the treatment of nasopharyngeal carcinoma patients[J]. Int J Radiat Oncol Biol Phys, 2017,98(5):996‐1001.DOI: 10.1016/j.ijrobp.2017.03.018. [38] Xie HJ, Yu YF, Sun XS, et al.Identifying optimal candidates for induction chemotherapy among stage II‐IVa nasopharyngeal carcinoma based on pretreatment Epstein‐Barr virus DNA and nodal maximal standard uptake values of [(18) F]‐fluorodeoxyglucose positron emission tomography[J]. Cancer Med, 2020,9(23):8852‐8863.DOI: 10.1002/cam4.3500. [39] Yang S, Zhao K, Ding X, et al.Prognostic significance of hematological markers for patients with nasopharyngeal carcinoma: a meta‐analysis[J]. J Cancer, 2019,10(11):2568‐2577.DOI: 10.7150/jca.26770. [40] Pan XB, Huang ST, Zhu XD.Neutrophil‐to‐lymphocyte ratio predicts the prognosis of stage II nasopharyngeal carcinoma[J]. Cancer Manag Res, 2019,11:8269‐8275.DOI: 10.2147/CMAR.S213264. [41] Liu J, Wei C, Tang H, et al.The prognostic value of the ratio of neutrophils to lymphocytes before and after intensity modulated radiotherapy for patients with nasopharyngeal carcinoma[J]. Medicine (Baltimore), 2020,99(2):e18545.DOI: 10.1097/MD.0000000000018545. [42] Li JP, Chen SL, Peng SG, et al.Prognostic nomogram for patients with nasopharyngeal carcinoma incorporating hematological biomarkers and clinical characteristics[J]. Int J Biol Sci, 2018, 14(5): 549‐56.DOI: 10.7150/ijbs.24374.