Matched pair analysis for comparison of survival outcome of alternative regimens to standard three-weekly cisplatin-based concurrent chemoradiation of head and neck cancer

Background To compare head and neck cancer (HNC) patients treated with three-weekly versus weekly cisplatin-based or other chemotherapy-based concurrent chemoradiation (CRT) and CRT with versus without induction chemotherapy (ICT) to investigate differences in overall survival (OS) and cancer-specific survival (CSS). Methods HNC patients treated with definitive or adjuvant CRT at Roswell Park Comprehensive Cancer Center between 2003 and 2017 were retrospectively reviewed. Propensity score matching was performed to obtain three sets of balanced matched pairs: three-weekly and weekly cisplatin CRT, three weekly and non-cisplatin CRT, CRT with and without ICT. Multivariate Cox regression and Kaplan-Meier analyses were used to estimate and compare survival outcomes. Results A total of 623 patients received either definitive (81%) or post-operative (19%) RT. Of these, 283 patients concurrently received three-weekly cisplatin (45%); 189 patients (30%) received weekly cisplatin; 151 patients (24%) received non-cisplatin regimen. Median follow-up was 55.4 months (interquartile range, 38.0–88.7). Patients who received CRT alone and those who received ICT and CRT had no difference in 5-year OS (51.5% and 41.0% respectively, P=0.53) and CSS (64.9% and 49.7% respectively, P=0.21). Compared to patients who received three-weekly cisplatin, patients who received weekly cisplatin had no difference in 5-year OS (59.3% vs. 54.1%, P=0.35) and CSS (70.3% vs. 62.4%, P=0.09); patients who received non-cisplatin CRT also had no difference in 5-year OS (54.5% vs. 58.3%, P=0.51) and CSS (67.5% vs. 64.7%, P=0.45). Conclusions No significant difference in OS and CSS was observed in any of the three pairs of CRT regimens. ICT prior to CRT did not improve survival of CRT alone. Non-cisplatin and weekly cisplatin regimens did not prove to be inferior to the standard three-weekly cisplatin.

[1]  C. Qian,et al.  Induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: long-term results of a phase III multicentre randomised controlled trial. , 2019, European journal of cancer.

[2]  Anurag K. Singh,et al.  The effect of time between diagnosis and initiation of treatment on outcomes in patients with head and neck squamous cell carcinoma. , 2019, Oral oncology.

[3]  Yingqin Li,et al.  Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. , 2019, The New England journal of medicine.

[4]  K. Prabhash,et al.  Low-Dose vs. High-Dose Cisplatin: Lessons Learned From 59 Chemoradiotherapy Trials in Head and Neck Cancer , 2019, Frontiers in Oncology.

[5]  O. Riesterer,et al.  3-weekly or weekly cisplatin concurrently with radiotherapy for patients with squamous cell carcinoma of the head and neck – a multicentre, retrospective analysis , 2019, Radiation Oncology.

[6]  Christopher U. Jones,et al.  Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial , 2019, The Lancet.

[7]  C. R. Leemans,et al.  Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial , 2019, The Lancet.

[8]  E. Genden,et al.  Cisplatin Every 3 Weeks Versus Weekly With Definitive Concurrent Radiotherapy for Squamous Cell Carcinoma of the Head and Neck. , 2018, Journal of the National Cancer Institute.

[9]  J. Bourhis,et al.  Avelumab-cetuximab-radiotherapy (RT) versus standards of care (SoC) in locally advanced squamous cell carcinoma of the head and neck (SCCHN): Safety phase of the randomized trial GORTEC 2017-01 (REACH). , 2018 .

[10]  Sang Gon Park,et al.  Comparison of standard-dose 3-weekly cisplatin and low-dose weekly cisplatin for concurrent chemoradiation of patients with locally advanced head and neck squamous cell cancer , 2018, Medicine.

[11]  S. Kannan,et al.  Once-a-Week Versus Once-Every-3-Weeks Cisplatin Chemoradiation for Locally Advanced Head and Neck Cancer: A Phase III Randomized Noninferiority Trial. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  D. Ghosh,et al.  Survival impact of induction chemotherapy in advanced head and neck cancer: A National Cancer Database analysis , 2017, Head & neck.

[13]  Anurag K. Singh,et al.  Smoking cessation is associated with improved survival in oropharynx cancer treated by chemoradiation , 2016, The Laryngoscope.

[14]  P. Pai,et al.  Conventional radiotherapy versus concurrent chemoradiotherapy versus accelerated radiotherapy in locoregionally advanced carcinoma of head and neck: Results of a prospective randomized trial , 2016, Head & neck.

[15]  Shing-Hwa Liu,et al.  Outcomes of Induction Chemotherapy for Head and Neck Cancer Patients , 2016, Medicine.

[16]  Dong-Wan Kim,et al.  Effect of induction chemotherapy on survival in locally advanced head and neck squamous cell carcinoma treated with concurrent chemoradiotherapy: Single center experience , 2016, Head & neck.

[17]  W. Shi,et al.  Efficacy of concurrent cetuximab vs. 5-fluorouracil/carboplatin or high-dose cisplatin with intensity-modulated radiation therapy (IMRT) for locally-advanced head and neck cancer (LAHNSCC). , 2014, Oral oncology.

[18]  E. Vokes,et al.  Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  M. Fujii,et al.  Randomized phase II/III trial of post-operative chemoradiotherapy comparing 3-weekly cisplatin with weekly cisplatin in high-risk patients with squamous cell carcinoma of head and neck: Japan Clinical Oncology Group Study (JCOG1008). , 2014, Japanese journal of clinical oncology.

[20]  I. Floriani,et al.  Concomitant chemoradiation (CRT) or cetuximab/RT (CET/RT) versus induction Docetaxel/ Cisplatin/5-Fluorouracil (TPF) followed by CRT or CET/RT in patients with Locally Advanced Squamous Cell Carcinoma of Head and Neck (LASCCHN). A randomized phase III factorial study (NCT01086826). , 2014 .

[21]  R. Weber,et al.  Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  F. Khuri,et al.  Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. , 2013, The Lancet. Oncology.

[23]  D. Tsan,et al.  The comparison between weekly and three-weekly cisplatin delivered concurrently with radiotherapy for patients with postoperative high-risk squamous cell carcinoma of the oral cavity , 2012, Radiation oncology.

[24]  K. Ang,et al.  Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. , 2012, International journal of radiation oncology, biology, physics.

[25]  P. Austin,et al.  Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies , 2010, Pharmaceutical statistics.

[26]  B. Mohanti,et al.  Concomitant chemoradiation versus radical radiotherapy in advanced squamous cell carcinoma of oropharynx and nasopharynx using weekly cisplatin: a phase II randomized trial. , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.

[27]  J. Pignon,et al.  Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[28]  Christopher U. Jones,et al.  Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. , 2006, The New England journal of medicine.

[29]  J. Jacobs,et al.  Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. , 2004, The New England journal of medicine.

[30]  Jacques Bernier,et al.  Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. , 2004, The New England journal of medicine.

[31]  G. Calais,et al.  Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[32]  R. Weber,et al.  Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. , 2003, The New England journal of medicine.

[33]  J. Ensley,et al.  An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  E. Cohen-Jonathan,et al.  Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced head and neck carcinoma: final report of a randomized trial. , 1996, International journal of radiation oncology, biology, physics.

[35]  L. Collette,et al.  Larynx preservation in pyriform sinus cancer: preliminary results of a European Organization for Research and Treatment of Cancer phase III trial. EORTC Head and Neck Cancer Cooperative Group. , 1996, Journal of the National Cancer Institute.

[36]  W. Hong,et al.  Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. , 1991, The New England journal of medicine.