Primary tumor regression speed after radiotherapy and its prognostic significance in nasopharyngeal carcinoma: a retrospective study

BMC Cancer

Ning Zhang³  Shao-Bo Liang¹  Yan-Ming Deng²  Rui-Liang Lu⁵  Hai-Yang Chen¹  Hai Zhao⁵  Zhi-Qian Lv³  Shao-Qiang Liang³  Lin Yang¹  Dong-Sheng Liu⁴  Yong Chen¹ 

[1] Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, People’s Republic of China

[2] Chemotherapy Department of Head & Neck & Chest Carcinoma, Cancer Center, The First People’s Hospital of Foshan, 81 Lingnan Street North, Foshan, People’s Republic of China

[3] Radiotherapy Department of Nasopharyngeal Carcinoma, Cancer Center, The First People’s Hospital of Foshan, 81 Lingnan Street North, Foshan, People’s Republic of China

[4] Department of Medical Statistics, The First People’s Hospital of Foshan, 81 Lingnan Street North, Foshan, People’s Republic of China

[5] Department of Imaging Diagnosis, The First People’s Hospital of Foshan, 81 Lingnan Street North, Foshan, People’s Republic of China

关键词: Survival;    Tumor regression;    Radiotherapy;    Nasopharyngeal carcinoma;   

Others  :  859020
DOI  :  10.1186/1471-2407-14-136

 received in 2013-10-12, accepted in 2014-02-21,  发布年份 2014

【 摘 要 】

Background

To observe the primary tumor (PT) regression speed after radiotherapy (RT) in nasopharyngeal carcinoma (NPC) and evaluate its prognostic significance.

Methods

One hundred and eighty-eight consecutive newly diagnosed NPC patients were reviewed retrospectively. All patients underwent magnetic resonance imaging and fiberscope examination of the nasopharynx before RT, during RT when the accumulated dose was 46–50 Gy, at the end of RT, and 3–4 months after RT.

Results

Of 188 patients, 40.4% had complete response of PT (CRPT), 44.7% had partial response of PT (PRPT), and 14.9% had stable disease of PT (SDPT) at the end of RT. The 5-year overall survival (OS) rates for patients with CRPT, PRPT, and SDPT at the end of RT were 84.0%, 70.7%, and 44.3%, respectively (P < 0.001, hazard ratio [HR] = 2.177, 95% confidence interval [CI] = 1.480-3.202). The 5-year failure-free survival (FFS) and distant metastasis-free survival (DMFS) rates also differed significantly (87.8% vs. 74.3% vs. 52.7%, P = 0.001, HR = 2.148, 95% CI, 1.384-3.333; 91.7% vs. 84.7% vs. 66.1%, P = 0.004, HR = 2.252, 95% CI = 1.296-3.912). The 5-year local relapse–free survival (LRFS) rates were not significantly different (95.8% vs. 86.0% vs. 81.8%, P = 0.137, HR = 1.975, 95% CI, 0.976-3.995). By multivariate analyses, the PT regression speed at the end of RT was the only independent prognostic factor of OS, FFS, and DMFS (P < 0.001, P = 0.001, and P = 0.004, respectively). The 5-year FFS rates for patients with CRPT during RT and CRPT only at the end of RT were 80.2% and 97.1%, respectively (P = 0.033). For patients with persistent PT at the end of RT, the 5-year LRFS rates of patients without and with boost irradiation were 87.1% and 84.6%, respectively (P = 0.812).

Conclusions

PT regression speed at the end of RT was an independent prognostic factor of OS, FFS, and DMFS in NPC patients. Immediate strengthening treatment may be provided to patients with poor tumor regression at the end of RT.

【 授权许可】

   
2014 Zhang et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Lai SZ, Li WF, Chen L, Luo W, Chen YY, Liu LZ, Sun Y, Lin AH, Liu MZ, Ma J: How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients? Int J Radiat Oncol Biol Phys 2011, 80:661-668.
• [2]Peng G, Wang T, Yang KY, Zhang S, Zhang T, Li Q, Han J, Wu G: A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs. conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma. Radiother Oncol 2012, 104:286-293.
• [3]Fang FM, Chien CY, Tsai WL, Chen HC, Hsu HC, Lui CC, Huang TL, Huang HY: Quality of life and survival outcome for patients with nasopharyngeal carcinoma receiving three-dimensional conformal radiotherapy vs. intensity-modulated radiotherapy-a longitudinal study. Int J Radiat Oncol Biol Phys 2008, 72:356-364.
• [4]Xiao WW, Huang SM, Han F, Wu SX, Lu LX, Lin CG, Deng XW, Lu TX, Cui NJ, Zhao C: Local control, survival, and late toxicities of locally advanced nasopharyngeal carcinoma treated by simultaneous modulated accelerated radiotherapy combined with cisplatin concurrent chemotherapy: long-term results of a phase 2 study. Cancer 2011, 117:1874-1883.
• [5]Edge SB, Compton CC: The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010, 17:1471-1474.
• [6]Chen L, Mao YP, Xie FY, Liu LZ, Sun Y, Tian L, Tang LL, Lin AH, Li L, Ma J: The seventh edition of the UICC/AJCC staging system for nasopharyngeal carcinoma is prognostically useful for patients treated with intensity-modulated radiotherapy from an endemic area in China. Radiother Oncol 2012, 104:331-337.
• [7]Chua DT, Sham JS, Kwong DL, Tai KS, Wu PM, Lo M, Yung A, Choy D, Leong L: Volumetric analysis of tumor extent in nasopharyngeal carcinoma and correlation with treatment outcome. Int J Radiat Oncol Biol Phys 1997, 39:711-719.
• [8]Guo R, Sun Y, Yu XL, Yin WJ, Li WF, Chen YY, Mao YP, Liu LZ, Li L, Lin AH, Ma J: Is primary tumor volume still a prognostic factor in intensity modulated radiation therapy for nasopharyngeal carcinoma? Radiother Oncol 2012, 104:294-299.
• [9]Liang SB, Deng YM, Zhang N, Lu RL, Zhao H, Chen HY, Li SE, Liu DS, Chen Y: Prognostic significance of maximum primary tumor diameter in nasopharyngeal carcinoma. BMC Cancer 2013, 13:260. BioMed Central Full Text
• [10]Chong VF, Zhou JY, Khoo JB, Chan KL, Huang J: Correlation between MR imaging-derived nasopharyngeal carcinoma tumor volume and TNM system. Int J Radiat Oncol Biol Phys 2006, 64:72-76.
• [11]Chai SJ, Pua KC, Saleh A, Yap YY, Lim PV, Subramaniam SK, Lum CL, Krishnan G, Mahiyuddin WR, Teo SH, Khoo AS, Yap LF, Malaysian NPC Study Group: Clinical significance of plasma Epstein-Barr Virus DNA loads in a large cohort of Malaysian patients with nasopharyngeal carcinoma. J Clin Virol 2012, 55:34-39.
• [12]Leung SF, Chan AT, Zee B, Ma B, Chan LY, Johnson PJ, Lo YM: Pretherapy quantitative measurement of circulating Epstein-Barr virus DNA is predictive of posttherapy distant failure in patients with early-stage nasopharyngeal carcinoma of undifferentiated type. Cancer 2003, 98:288-291.
• [13]Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG: New guidelines to evaluate the response to treatment in solid tumors. European organization for research and treatment of cancer, national cancer institute of the United States, national cancer institute of Canada. J Natl Cancer Inst 2000, 92:205-216.
• [14]Chen QY, Wen YF, Guo L, Liu H, Huang PY, Mo HY, Li NW, Xiang YQ, Luo DH, Qiu F, Sun R, Deng MQ, Chen MY, Hua YJ, Guo X, Cao KJ, Hong MH, Qian CN, Mai HQ: Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial. J Natl Cancer Inst 2011, 103:1761-1770.
• [15]Lim AM, Corry J, Collins M, Peters L, Hicks RJ, D’Costa I, Coleman A, Chua M, Solomon B, Rischin D: A phase II study of induction carboplatin and gemcitabine followed by chemoradiotherapy for the treatment of locally advanced nasopharyngeal carcinoma. Oral Oncol 2013, 49:468-474.
• [16]Chen Y, Liu MZ, Liang SB, Zong JF, Mao YP, Tang LL, Guo Y, Lin AH, Zeng XF, Ma J: Preliminary results of a prospective randomized trial comparing concurrent chemoradiotherapy plus adjuvant chemotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma in endemic regions of china. Int J Radiat Oncol Biol Phys 2008, 71:1356-1364.
• [17]Kwong DL, Nicholls J, Wei WI, Chua DT, Sham JS, Yuen PW, Cheng AC, Wan KY, Kwong PW, Choy DT: The time course of histologic remission after treatment of patients with nasopharyngeal carcinoma. Cancer 1999, 85:1446-1453.
• [18]Mäntylä M, Kortekangas AE, Valavaara RA, Nordman EM: Tumor regression during radiation treatment as a guide to prognosis. Br J Radiol 1979, 52:972-977.
• [19]Chan AT, Teo PM, Ngan RK, Leung TW, Lau WH, Zee B, Leung SF, Cheung FY, Yeo W, Yiu HH, Yu KH, Chiu KW, Chan DT, Mok T, Yuen KT, Mo F, Lai M, Kwan WH, Choi P, Johnson PJ: Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial. J Clin Oncol 2002, 20:2038-2044.
• [20]Chan AT, Leung SF, Ngan RK, Teo PM, Lau WH, Kwan WH, Hui EP, Yiu HY, Yeo W, Cheung FY, Yu KH, Chiu KW, Chan DT, Mok TS, Yau S, Yuen KT, Mo FK, Lai MM, Ma BB, Kam MK, Leung TW, Johnson PJ, Choi PH, Zee BC: Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst 2005, 97:536-539.
• [21]Lin JC, Jan JS, Hsu CY, Liang WM, Jiang RS, Wang WY: Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival. J Clin Oncol 2003, 21:631-637.
• [22]Zhang L, Zhao C, Peng PJ, Lu LX, Huang PY, Han F, Wu SX: Phase III study comparing standard radiotherapy with or without weekly oxaliplatin in treatment of locoregionally advanced nasopharyngeal carcinoma: preliminary results. J Clin Oncol 2005, 23:8461-8468.
• [23]Baujat B, Audry H, Bourhis J, Chan AT, Onat H, Chua DT, Kwong DL, Al-Sarraf M, Chi KH, Hareyama M, Leung SF, Thephamongkhol K, Pignon JP, MAC-NPC Collaborative Group: Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients. Int J Radiat Oncol Biol Phys 2006, 64:47-56.
• [24]Langendijk JA, Leemans CR, Buter J, Berkhof J, Slotman BJ: The additional value of chemotherapy to radiotherapy in locally advanced nasopharyngeal carcinoma: a meta-analysis of the published literature. J Clin Oncol 2004, 22:4604-4612.
• [25]Rossi A, Molinari R, Boracchi P, del Vecchio M, Marubini E, Nava M, Morandi L, Zucali R, Pilotti S, Grandi C: Adjuvant chemotherapy with vincristine, cyclophosphamide and doxorubicin after radiotherapy in local-regional nasopharyngeal cancer: results of a 4 year multi-center randomized study. J Clin Oncol 1988, 6:1401-1410.
• [26]Chi KH, Chang YC, Guo WY, Leung MJ, Shiau CY, Chen SY, Wang LW, Lai YL, Hsu MM, Lian SL, Chang CH, Liu TW, Chin YH, Yen SH, Perng CH, Chen KY: A phase III study of adjuvant chemotherapy in advanced nasopharyngeal carcinoma patients. Int J Radiat Oncol Biol Phys 2002, 52:1238-1244.
• [27]Chen L, Hu CS, Chen XZ, Hu GQ, Cheng ZB, Sun Y, Li WX, Chen YY, Xie FY, Liang SB, Chen Y, Xu TT, Li B, Long GX, Wang SY, Zheng BM, Guo Y, Sun Y, Mao YP, Tang LL, Chen YM, Liu MZ, Ma J: Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol 2012, 13:163-171.
• [28]Jaulerry C, Dubray B, Brunin F, Rodriguez J, Point D, Blaszka B, Asselain B, Mosseri V, Brugere J, Cosset JM: Prognostic value of tumor regression during radiotherapy for head and neck cancer: a prospective study. Int J Radiat Oncol Biol Phys 1995, 33:271-279.
• [29]Bataini JP, Jaulerry C, Brunin F, Ponvert D, Ghossein NA: Significance and therapeutic implications of tumor regression following radiotherapy in patients treated for squamous cell carcinoma of the oropharynx and pharyngolarynx. Head Neck 1990, 12:41-49.
• [30]Sun Y, Tang LL, Chen L, Li WF, Mao YP, Liu LZ, Lin AH, Li L, Ma J: Promising treatment outcomes of intensity-modulated radiation therapy for nasopharyngeal carcinoma patients with N0 disease according to the seventh edition of the AJCC staging system. BMC Cancer 2012, 12:68. BioMed Central Full Text
• [31]Lee AW, Poon YF, Foo W, Law SC, Cheung FK, Chan DK, Tung SY, Thaw M, Ho JH: Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976–1985: overall survival and patterns of failure. Int J Radiat Oncol Biol Phys 1992, 23:261-270.
• [32]Wang XS, Hu CS, Wu YR, Feng Y: Influence of speed in tumor regression on prognosis of nasopharyngeal carcinoma. Chin J of Radiat Oncol 2005, 14:6-9.
• [33]Li ZQ, Xia YF, Liu Q, Yi W, Liu XF, Han F, Luo W, Lu TX: Radiotherapy-related typing in 842 patients in canton with nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2006, 66:1011-1016.
• [34]Tate DJ, Adler JR Jr, Chang SD, Marquez S, Eulau SM, Fee WE, Pinto H, Goffinet DR: Stereotactic radiosurgical boost following radiotherapy in primary nasopharyngeal carcinoma: impact on local control. Int J Radiat Oncol Biol Phys 1999, 45:915-921.
• [35]Hara W, Loo BW Jr, Goffinet DR, Chang SD, Adler JR, Pinto HA, Fee WE, Kaplan MJ, Fischbein NJ, Le QT: Excellent local control with stereotactic radiotherapy boost after external beam radiotherapy in patients with nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2008, 71:393-400.
• [36]Yau TK, Sze WM, Lee WM, Yeung MW, Leung KC, Hung WM, Chan WI: Effectiveness of brachytherapy and fractionated stereotactic radiotherapy boost for persistent nasopharyngeal carcinoma. Head Neck 2004, 26:1024-1030.
• [37]Leung TW, Wong VY, Sze WK, Lui CM, Tung SY: High-dose-rate intracavitary brachytherapy boost for early T stage nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2008, 70:361-367.
• [38]Yeo R, Fong KW, Hee SW, Chua ET, Tan T, Wee J: Brachytherapy boost for T1/T2 nasopharyngeal carcinoma. Head Neck 2009, 31:1610-1618.
• [39]Schinagl DA, Marres HA, Kappelle AC, Merkx MA, Pop LA, Verstappen SM, Kaanders JH: External beam radiotherapy with endocavitary boost for nasopharyngeal cancer: treatment results and late toxicity after extended follow-up. Int J Radiat Oncol Biol Phys 2010, 78:689-695.
• [40]Sham JS, Wei WI, Kwan WH, Chan CW, Kwong WK, Choy D: Nasopharyngeal carcinoma. Pattern of tumor regression after radiotherapy. Cancer 1990, 65:216-220.