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. 2019 Aug:95:106-114.
doi: 10.1016/j.oraloncology.2019.06.001. Epub 2019 Jun 15.

Role of chemotherapy in 5000 patients with head and neck cancer treated by curative surgery: A subgroup analysis of the meta-analysis of chemotherapy in head and neck cancer

Etienne Dauzier  1 , Benjamin Lacas  1 , Pierre Blanchard  2 , Quynh-Thu Le  3 , Christian Simon  4 , Gregory Wolf  5 , François Janot  6 , Masatoshi Horiuchi  7 , Jeffrey S Tobias  8 , James Moon  9 , John Simes  10 , Vinay Deshmane  11 , Jean-Jacques Mazeron  12 , Samir Mehta  13 , Branko Zaktonik  14 , Minoru Tamura  15 , Elizabeth Moyal  16 , Lisa Licitra  17 , Catherine Fortpied  18 , Bruce G Haffty  19 , Maria Grazia Ghi  20 , Vincent Gregoire  21 , Jonathan Harris  22 , Jean Bourhis  23 , Anne Aupérin  24 , Jean-Pierre Pignon  1 ; MACH-NC Collaborative Group
Affiliations

Role of chemotherapy in 5000 patients with head and neck cancer treated by curative surgery: A subgroup analysis of the meta-analysis of chemotherapy in head and neck cancer

Etienne Dauzier et al. Oral Oncol. 2019 Aug.

Abstract

Objective: To evaluate the effect of chemotherapy added to a surgical locoregional treatment (LRT) for patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Materials and methods: We studied the sub-group of trials with surgical LRT included in the meta-analysis on chemotherapy in head and neck cancer (MACH-NC). Data from published and unpublished randomized trials comparing the addition of chemotherapy to LRT in HNSCC patients were sought using electronic database searching for the period 1965-2000, hand searching and by contacting experts in the field. Trials with less than 60 patients, or preoperative radiotherapy or where the type of LRT could not be individually determined were excluded. All individual patient data were checked for internal consistency, compared with published reports, and validated with trialists. Data were pooled using a fixed-effect model. Heterogeneity was assessed using Cochrane test and I2 statistic.

Results: Twenty-four trials were eligible (5000 patients). Chemotherapy improved overall survival (HR = 0.92 [95%CI: 0.85-0.99] p = 0.02). There was a significant interaction between treatment effect and timing of chemotherapy (p = 0.08 at pre-specified threshold of 0.10) with a greater effect for concomitant chemotherapy (HR = 0.79, 95%CI: 0.69-0.92). The benefit of chemotherapy was greater in women (HRwomen = 0.63, 95%CI: 0.50-0.80) compared to men (HRmen = 0.96, 95%CI: 0.89-1.04; p for interaction = 0.001).

Conclusions: This analysis confirmed the benefit of concomitant chemotherapy added to surgical LRT. The role of induction therapy as yet to be determined as it did not improve OS. Women may benefit more than men from chemotherapy.

Keywords: Chemotherapy; Head and neck cancer; Individual patient data; Meta-analysis; Randomized trial; Squamous cell carcinoma; Surgery.

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Conflict of interest statement

Conflict Of Interest statement

None declared

Figures

Figure 1:
Figure 1:. Hazard ratio of death with loco-regional treatment plus chemotherapy versus locoregional treatment alone.
This analysis was performed using a fixed-effect model. Heterogeneity is discussed in eTable 6 and in the beginning of Discussion section. The broken line and center of the black diamond correspond to overall pooled hazard ratio (HR) and the horizontal tip of the diamond is the 95% confidence interval (95%CI). The center of the black square corresponds to the HR of trials. The area of the square and the variance of (O-E) are proportional to the number of deaths in each trial. Trials are ordered chronologically (oldest at the top of figure). CT = Chemotherapy, LRT = Loco-regional treatment; O-E = observed minus expected, I2 = Higgins statistic for heterogeneity, No. = Number. In HNCP trial, the arm on induction CT and the one on induction plus maintenance CT were pooled. Trial group abbreviations: AHNTG = Australian Head and neck Trial Group, BNH = B. Nanavati Hospital / Mumbai Group (India), EORTC = European Organisation for Research and Treatment of Cancer, GETTEC = Groupe d’Etude des Tumeurs de la Tête Et du Cou (France), GSTTC = Gruppo di Studio sui Tumori della Testa et del Collo (Italy), HNCP = Head and Neck Contract Program (USA), HNU = Head and Neck UFT (Japan), , INT = US INTer group trial, JHCFUS = Japanese HexyCarbanoyl 5-FluoroUracil Study, KKD = Kanto Koshinetsu District (Japan), LOHNG = Ljubljana Oncology Head and Neck Group (Slovenia), RTOG = Radiation Therapy Oncology Group (USA), SWOG = Southwest Oncology Group (USA), TMH = Tata Memorial Hospital (India), UKHAN = United Kingdom Head And Neck (UKCCR head and Neck Collaborative Group, UK), Yale = Yale University (USA).
Figure 2:
Figure 2:. Overall survival curves by treatment arm for all trials and for trial subset defined by timing of chemotherapy
The slopes of the broken lines from year 7 to year 8 are based on the overall death rates in the seventh and subsequent years. Absolute differences are given with their 95% confidence interval. LRT = Loco-regional treatment, CT = Chemotherapy. a) All trials; b) Adjuvant chemotherapy trials; c) Induction chemotherapy trials; d) Concomitant chemotherapy trials.
Figure 3:
Figure 3:. Hazard ratio of death with loco-regional treatment plus chemotherapy versus loco-regional treatment alone by patient’s characteristics.
See Figure 1 Legend for more explanations. p_inter: p-value of the test of interaction between individual characteristics and treatment effect. p_trend: p-value of the test for trend; PS = performance status. 95%CI = 95% confidence interval O-E = observed minus expected, No. = Number. (a) 4 980 patients included in univariate Cox model for interaction. (b) 4 829 patients included in univariate Cox model for interaction. (c) Missing data in 19 trials (completely missing for BNH003 (124 patients), Cologne (97), Creteil 82 (122), EORTC 24771 (231), EORTC 78-OCP (225), GETTECadj (286), JHCFUS (191), LOHNG97 (114), Pitie-74 (96), TMHR-4 (135), Toulouse (90), Yale80po (78). Only 2811 patients included in univariate Cox model for interaction (GSTTC86po and SWOG8006 had to be excluded because none of their patients had no patients included in the PS=0 category) (d) Only 2825 patients included in univariate Cox model for interaction because all trials had not included patients in all 4 categories of interest (GETTECneo2, BNH003, Cologne, Creteil-82, EORTC24771, EORTC24844, EORTC78-OCP, GSTTC86po, HNCP, KKD-86, Pitie-74, TMHR-4 ) (e) Information on stage was not available for 2 trials (Pitie74 (96) and TMHR-4 (135)).Only 4 405 patients included in univariate Cox model for interaction (BNH003, GSTTC86po and LOHNG97 were excluded because of the absence of stage I or II patients)
Figure 4:
Figure 4:. Overall survival curves by treatment arm for all trials according to sex.
On the right: men overall survival according to treatment. On the left: female overall survival according to treatment arm. The slopes of the broken lines from year 7 to year 8 are based on the overall death rates in the seventh and subsequent years. Absolute differences are given with 95% confidence interval. LRT = Loco-regional treatment, CT = Chemotherapy.
Figure 5:
Figure 5:. Cumulative incidence by treatment arm for each type of event (for overall analysis and for each timing of chemotherapy).
Given p values correspond to the comparisons of cumulative incidence between treated and non-treated patients (stratified Fine and Gray test). The top left figure represents overall analysis. CT = Chemotherapy; LRT = Locoregional treatment
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Comment in

  • Response to R. Jayaraj.
    Dauzier E, Lacas B, Blanchard P, Aupérin A, Pignon JP. Dauzier E, et al. Oral Oncol. 2020 Mar;102:104439. doi: 10.1016/j.oraloncology.2019.104439. Epub 2019 Nov 2. Oral Oncol. 2020. PMID: 31685291 No abstract available.

References

    1. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012: Globocan 2012. Int J Cancer. 2015;136:E359–E386. doi:10.1002/ijc.29210 - DOI - PubMed
    1. Baxi SS, Pinheiro LC, Patil SM, Pfister DG, Oeffinger KC, Elkin EB. Causes of death in long-term survivors of head and neck cancer: Competing Mortality in HNSCC Survivors. Cancer. 2014;120(10):1507–1513. doi:10.1002/cncr.28588 - DOI - PMC - PubMed
    1. Pignon J-P, Le Maître A, Maillard E, Bourhis J. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009;92:4–14. doi:10.1016/j.radonc.2009.04.014 - DOI - PubMed
    1. Fujiwara RJT, Burtness B, Husain ZA, et al. Treatment guidelines and patterns of care in oral cavity squamous cell carcinoma: Primary surgical resection vs. nonsurgical treatment. Oral Oncol. 2017;71:129137. doi:10.1016/j.oraloncology.2017.06.013 - DOI - PubMed
    1. Busch C-J, Tribius S, Schafhausen P, Knecht R. The current role of systemic chemotherapy in the primary treatment of head and neck cancer. Cancer Treat Rev. 2015;41(3):217–221. doi:10.1016/j.ctrv.2015.02.002 - DOI - PubMed

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