The Tumour Response to Induction Chemotherapy has Prognostic Value for Long-Term Survival Outcomes after Intensity-Modulated Radiation Therapy in Nasopharyngeal Carcinoma

Hao Peng, Lei Chen, Yuan Zhang, Wen-Fei Li, Yan-Ping Mao, Xu Liu, Fan Zhang, Rui Guo, Li-Zhi Liu, Li Tian, Ai-Hua Lin, Ying Sun, Jun Ma, Hao Peng, Lei Chen, Yuan Zhang, Wen-Fei Li, Yan-Ping Mao, Xu Liu, Fan Zhang, Rui Guo, Li-Zhi Liu, Li Tian, Ai-Hua Lin, Ying Sun, Jun Ma

Abstract

The prognostic value of the tumour response to induction chemotherapy (IC) for long-term survival outcomes after intensity-modulated radiation therapy in nasopharyngeal carcinoma (NPC) remains unknown. We retrospectively reviewed 1811 consecutive patients with newly diagnosed NPC treated using IMRT, and 399 eligible patients with pre- and post-induction chemotherapy magnetic resonance images were recruited. The clinicopathological features of patients with different tumour responses were compared using the Chi-square test or Fisher's exact test. Prognostic value was assessed using a multivariate Cox proportional hazards model. After IC, 101/399 (25.3%) patients had a complete tumour response overall (CR), 262 (65.7%) had a partial response (PR) and 36 (9.0%) had stable disease (SD). The 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) rates for CR vs. PR vs. SD were 90.0% vs. 79.0% vs. 58.2% (CR vs. PR: P1 = 0.007; CR vs. SD: P2 < 0.001; PR vs. SD: P3 = 0.004), 95.7% vs. 88.7% vs. 70.2% (P1 = 0.017, P2 < 0.001, P3 = 0.005), 92.0% vs. 87.4% vs. 74.3% (P1 = 0.162, P2 = 0.005, P3 = 0.029) and 95.9% vs. 88.8% vs. 81.8% (P1 = 0.024, P2 = 0.006, P3 = 0.268), respectively. Multivariate analysis identified that the tumour response to IC was an independent prognostic factor for DFS, OS and LRRFS.

Figures

Figure 1
Figure 1
Kaplan-Meier DFS (1A), OS (1B), DMFS (1C) and LRRFS (1D) curves for 399 patients with NPC receiving IMRT stratified as the CR, PR and SD groups based on overall tumour response after induction chemotherapy. Abbreviations: DFS = disease-free survival; OS = overall survival; LRRFS = local-regional relapse-free survival; DMFS = distant metastasis-free survival. CR = complete response; PR = partial response; SD = stable disease.
Figure 2
Figure 2
Kaplan-Meier DFS (2A), OS (2B), LRFS (2C) and DMFS (2D) curves for 399 patients with NPC receiving IMRT stratified as the CR, PR and SD groups based on the local tumour response after induction chemotherapy. Abbreviations: DFS = disease-free survival; OS = overall survival; LRFS = local relapse-free survival; DMFS = distant metastasis-free survival. CR = complete response; PR = partial response; SD = stable disease.
Figure 3
Figure 3
Kaplan-Meier DFS (3A), OS (3B), RRFS (3C) and DMFS (3D) curves for 399 patients with NPC receiving IMRT stratified as the CR, PR and SD groups based on the regional tumour response after induction chemotherapy. Abbreviations: DFS = disease-free survival; OS = overall survival; RRFS = regional relapse-free survival; DMFS = distant metastasis-free survival. CR = complete response; PR = partial response; SD = stable disease.

References

    1. Jemal A., Bray F. & Center M. M. Global cancer statistics. CA Cancer J Clin 61(2), p. 69–90 (2011).
    1. Al-Sarraf M., LeBlanc M. & Giri P. G. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 16(4), p. 1310–7 (1998).
    1. Chan A. T., Leung S. F. & Ngan R. K. Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 97(7), p. 536–9 (2005).
    1. Lee A. W., Lau W. H. & Tung S. Y. Preliminary results of a randomized study on therapeutic gain by concurrent chemotherapy for regionally-advanced nasopharyngeal carcinoma: NPC-9901 Trial by the Hong Kong Nasopharyngeal Cancer Study Group. J Clin Oncol. 23(28), p. 6966–75 (2005).
    1. Lin J. C., Jan J. S. & Hsu C. Y. Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival. J Clin Oncol. 21(4), p. 631–7 (2003).
    1. Wee J., Tan E. H. & Tai B. C. Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety. J Clin Oncol. 23(27), p. 6730–8 (2005).
    1. Hui E. P., Ma B. B. & Leung S. F. Randomized phase II trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma. J Clin Oncol. 27(2), p. 242–9 (2009).
    1. Fountzilas G., Ciuleanu E. & Bobos M. Induction chemotherapy followed by concomitant radiotherapy and weekly cisplatin versus the same concomitant chemoradiotherapy in patients with nasopharyngeal carcinoma: a randomized phase II study conducted by the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation. Ann Oncol. 23(2), p. 427–35 (2012).
    1. Lee A. W., Ngan R. K. & Tung S. Y. Preliminary results of trial NPC-0501 evaluating the therapeutic gain by changing from concurrent-adjuvant to induction-concurrent chemoradiotherapy, changing from fluorouracil to capecitabine, and changing from conventional to accelerated radiotherapy fractionation in patients with locoregionally advanced nasopharyngeal carcinoma. Cancer 121(8), p. 1328–38 (2015).
    1. Hareyama M., Sakata K. & Shirato H. A prospective, randomized trial comparing neoadjuvant chemotherapy with radiotherapy alone in patients with advanced nasopharyngeal carcinoma. Cancer 94(8), p. 2217–23 (2002).
    1. International Nasopharynx Cancer Study, G. and V.I. Trial. Preliminary results of a randomized trial comparing neoadjuvant chemotherapy (cisplatin, epirubicin, bleomycin) plus radiotherapy vs. radiotherapy alone in stage IV(> or = N2, M0) undifferentiated nasopharyngeal carcinoma: a positive effect on progression-free survival. Int J Radiat Oncol Biol Phys. 35(3), p. 463–9 (1996).
    1. Ma J., Mai H. Q. & Hong M. H. Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma. J Clin Oncol. 19(5), p. 1350–7 (2001).
    1. Bacci G., Longhi A. & Versari M. Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution. Cancer 106(5), p. 1154–61 (2006).
    1. Picci P., Rougraff B. T. & Bacci G. Prognostic significance of histopathologic response to chemotherapy in nonmetastatic Ewing’s sarcoma of the extremities. J Clin Oncol. 11(9), p. 1763–9 (1993).
    1. Visser J. H., Wessels G. & Hesseling P. B. Prognostic value of day 14 blast percentage and the absolute blast index in bone marrow of children with acute lymphoblastic leukemia. Pediatr Hematol Oncol. 18(3), p. 187–91 (2001).
    1. Liu L. T., Tang L. Q. & Chen Q. Y. The Prognostic Value of Plasma Epstein-Barr Viral DNA and Tumor Response to Neoadjuvant Chemotherapy in Advanced-Stage Nasopharyngeal Carcinoma. Int J Radiat Oncol Biol Phys. 93(4), p. 862–9 (2015).
    1. Edge S. B. & Compton C. C. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17(6), p. 1471–4 (2010).
    1. Therasse P., Arbuck S. G. & Eisenhauer E. A. 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. 92(3), p. 205–16 (2000).
    1. Airoldi M., Gabriele A. M. & Garzaro M. Induction chemotherapy with cisplatin and epirubicin followed by radiotherapy and concurrent cisplatin in locally advanced nasopharyngeal carcinoma observed in a non-endemic population. Radiother Oncol. 92(1), p. 105–10 (2009).
    1. Golden D. W., Rudra S. & Witt M. E. Outcomes of induction chemotherapy followed by concurrent chemoradiation for nasopharyngeal carcinoma. Oral Oncol. 49(3), p. 277–82 (2013).
    1. Guo S. S., Huang P. Y. & Chen Q. Y. The impact of smoking on the clinical outcome of locoregionally advanced nasopharyngeal carcinoma after chemoradiotherapy. Radiat Oncol. 9, p. 246 (2014).
    1. Sun X., Su S. & Chen C. Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities. Radiother Oncol. 110(3), p. 398–403 (2014).
    1. Hsu C. H., Chen C. L. & Hong R. L. Prognostic value of multidrug resistance 1, glutathione-S-transferase-pi and p53 in advanced nasopharyngeal carcinoma treated with systemic chemotherapy. Oncology. 62(4), p. 305–12 (2002).
    1. Larbcharoensub N., Leopairat J. & Sirachainan E. Association between multidrug resistance-associated protein 1 and poor prognosis in patients with nasopharyngeal carcinoma treated with radiotherapy and concurrent chemotherapy. Hum Pathol. 39(6), p. 837–45 (2008).
    1. Chow B. H., Chua D. T. & Sham J. S. Increased expression of annexin I is associated with drug-resistance in nasopharyngeal carcinoma and other solid tumors. Proteomics Clin Appl. 3(6), p. 654–62 (2009).
    1. Pan Y., Zhang Q. & Atsaves V. Suppression of Jab1/CSN5 induces radio- and chemo-sensitivity in nasopharyngeal carcinoma through changes to the DNA damage and repair pathways. Oncogene. 32(22), p. 2756–66 (2013).
    1. Chan A. T., Lo Y. M. & Zee B. Plasma Epstein-Barr virus DNA and residual disease after radiotherapy for undifferentiated nasopharyngeal carcinoma. J Natl Cancer Inst. 94(21), p. 1614–9 (2002).
    1. Lin J. C., Wang W. Y. & Chen K. Y. Quantification of plasma Epstein-Barr virus DNA in patients with advanced nasopharyngeal carcinoma. N Engl J Med. 350(24), p. 2461–70 (2004).
    1. Lo Y. M., Chan L. Y. & Chan A. T. Quantitative and temporal correlation between circulating cell-free Epstein-Barr virus DNA and tumor recurrence in nasopharyngeal carcinoma. Cancer Res. 59(21), p. 5452–5 (1999).
    1. Guo R., Sun Y. & Yu X. L. Is primary tumor volume still a prognostic factor in intensity modulated radiation therapy for nasopharyngeal carcinoma? Radiother Oncol. 104(3), p. 294–9 (2012).
    1. Tian Y. M., Xiao W. W. & Bai L. Impact of primary tumor volume and location on the prognosis of patients with locally recurrent nasopharyngeal carcinoma. Chin J Cancer 34(6), p. 247–53 (2015).
    1. Wan X. B., Wei L. & Li H. High pretreatment serum lactate dehydrogenase level correlates with disease relapse and predicts an inferior outcome in locally advanced nasopharyngeal carcinoma. Eur J Cancer 49(10), p. 2356–64 (2013).

Source: PubMed

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