Pretreatment Lymphocyte Count Predicts Benefit From Concurrent Chemotherapy With Radiotherapy in Oropharyngeal Cancer

James M Price; Hitesh B Mistry; Guy Betts; Eleanor J Cheadle; Lynne Dixon; Kate Garcez; Tim Illidge; Zsuzsanna Iyizoba-Ebozue; Lip Wai Lee; Andrew McPartlin; Robin J D Prestwich; Savvas Papageorgiou; Dylan J Pritchard; Andrew Sykes; Catharine M West; David J Thomson

doi:10.1200/JCO.21.01991

Pretreatment Lymphocyte Count Predicts Benefit From Concurrent Chemotherapy With Radiotherapy in Oropharyngeal Cancer

James M Price, Hitesh B Mistry, Guy Betts, Eleanor J Cheadle, Lynne Dixon, Kate Garcez, Tim Illidge, Zsuzsanna Iyizoba-Ebozue, Lip Wai Lee, Andrew McPartlin, Robin J D Prestwich, Savvas Papageorgiou, Dylan J Pritchard, Andrew Sykes, Catharine M West, David J Thomson

Research output: Contribution to journal › Article › peer-review

Abstract

PURPOSE: There is a need to refine the selection of patients with oropharyngeal squamous cell carcinoma (OPSCC) for treatment de-escalation. We investigated whether pretreatment absolute lymphocyte count (ALC) predicted overall survival (OS) benefit from the addition of concurrent chemotherapy to radical radiotherapy.

PATIENTS AND METHODS: This was an observational study of consecutive OPSCCs treated by curative-intent radiotherapy, with or without concurrent chemotherapy (n = 791) with external, independent validation from a separate institution (n = 609). The primary end point was OS at 5 years. Locoregional control (LRC) was assessed using competing risk regression as a secondary end point. Previously determined prognostic factors were used in a multivariable Cox proportional hazards model to assess the prognostic importance of ALC and the interaction between ALC and cisplatin chemotherapy use.

RESULTS: Pretreatment ALC was prognostic for 5-year OS on multivariable analysis (hazard ratio [HR] 0.64; 95% CI, 0.42 to 0.98; P = .04). It also predicted benefit from the use of concurrent cisplatin chemotherapy, with a significant interaction between cisplatin chemotherapy and pretreatment ALC (likelihood ratio test, P = .04): higher ALC count reduced the 5-year OS benefit compared with radiotherapy alone (HR 2.53; 95% CI, 1.03 to 6.19; P = .043). This was likely driven by an effect on LRC up to 5 years (interaction subdistribution HR 2.29; 95% CI, 0.68 to 7.71; P = .094). An independent validation cohort replicated the OS (HR 2.53; 95% CI, 0.98 to 6.52; P = .055) and LRC findings (interaction subdistribution HR 3.43; 95% CI, 1.23 to 9.52; P = .018).

CONCLUSION: For OPSCC, the pretreatment ALC is prognostic for OS and also predicts benefit from the addition of cisplatin chemotherapy to radiotherapy. These findings require prospective evaluation, and could inform the selection of good prognosis patients for a de-escalation trial.

Original language	English
Pages (from-to)	JCO2101991
Journal	Journal of clinical oncology : official journal of the American Society of Clinical Oncology
DOIs	https://doi.org/10.1200/JCO.21.01991
Publication status	E-pub ahead of print - 6 Apr 2022

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Manchester Cancer Research Centre

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10.1200/JCO.21.01991

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Price, J. M., Mistry, H. B., Betts, G., Cheadle, E. J., Dixon, L., Garcez, K., Illidge, T., Iyizoba-Ebozue, Z., Lee, L. W., McPartlin, A., Prestwich, R. J. D., Papageorgiou, S., Pritchard, D. J., Sykes, A., West, C. M., & Thomson, D. J. (2022). Pretreatment Lymphocyte Count Predicts Benefit From Concurrent Chemotherapy With Radiotherapy in Oropharyngeal Cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, JCO2101991. Advance online publication. https://doi.org/10.1200/JCO.21.01991

@article{1878cfac815d4e0bb3c51ccc0403cf54,

title = "Pretreatment Lymphocyte Count Predicts Benefit From Concurrent Chemotherapy With Radiotherapy in Oropharyngeal Cancer",

abstract = "PURPOSE: There is a need to refine the selection of patients with oropharyngeal squamous cell carcinoma (OPSCC) for treatment de-escalation. We investigated whether pretreatment absolute lymphocyte count (ALC) predicted overall survival (OS) benefit from the addition of concurrent chemotherapy to radical radiotherapy.PATIENTS AND METHODS: This was an observational study of consecutive OPSCCs treated by curative-intent radiotherapy, with or without concurrent chemotherapy (n = 791) with external, independent validation from a separate institution (n = 609). The primary end point was OS at 5 years. Locoregional control (LRC) was assessed using competing risk regression as a secondary end point. Previously determined prognostic factors were used in a multivariable Cox proportional hazards model to assess the prognostic importance of ALC and the interaction between ALC and cisplatin chemotherapy use.RESULTS: Pretreatment ALC was prognostic for 5-year OS on multivariable analysis (hazard ratio [HR] 0.64; 95% CI, 0.42 to 0.98; P = .04). It also predicted benefit from the use of concurrent cisplatin chemotherapy, with a significant interaction between cisplatin chemotherapy and pretreatment ALC (likelihood ratio test, P = .04): higher ALC count reduced the 5-year OS benefit compared with radiotherapy alone (HR 2.53; 95% CI, 1.03 to 6.19; P = .043). This was likely driven by an effect on LRC up to 5 years (interaction subdistribution HR 2.29; 95% CI, 0.68 to 7.71; P = .094). An independent validation cohort replicated the OS (HR 2.53; 95% CI, 0.98 to 6.52; P = .055) and LRC findings (interaction subdistribution HR 3.43; 95% CI, 1.23 to 9.52; P = .018). CONCLUSION: For OPSCC, the pretreatment ALC is prognostic for OS and also predicts benefit from the addition of cisplatin chemotherapy to radiotherapy. These findings require prospective evaluation, and could inform the selection of good prognosis patients for a de-escalation trial.",

author = "Price, {James M} and Mistry, {Hitesh B} and Guy Betts and Cheadle, {Eleanor J} and Lynne Dixon and Kate Garcez and Tim Illidge and Zsuzsanna Iyizoba-Ebozue and Lee, {Lip Wai} and Andrew McPartlin and Prestwich, {Robin J D} and Savvas Papageorgiou and Pritchard, {Dylan J} and Andrew Sykes and West, {Catharine M} and Thomson, {David J}",

year = "2022",

month = apr,

day = "6",

doi = "10.1200/JCO.21.01991",

language = "English",

pages = "JCO2101991",

journal = "Journal of clinical oncology : official journal of the American Society of Clinical Oncology",

issn = "0732-183X",

publisher = "American Society of Clinical Oncology",

}

Price, JM, Mistry, HB, Betts, G, Cheadle, EJ, Dixon, L, Garcez, K, Illidge, T, Iyizoba-Ebozue, Z, Lee, LW, McPartlin, A, Prestwich, RJD, Papageorgiou, S, Pritchard, DJ, Sykes, A, West, CM & Thomson, DJ 2022, 'Pretreatment Lymphocyte Count Predicts Benefit From Concurrent Chemotherapy With Radiotherapy in Oropharyngeal Cancer', Journal of clinical oncology : official journal of the American Society of Clinical Oncology, pp. JCO2101991. https://doi.org/10.1200/JCO.21.01991

TY - JOUR

T1 - Pretreatment Lymphocyte Count Predicts Benefit From Concurrent Chemotherapy With Radiotherapy in Oropharyngeal Cancer

AU - Price, James M

AU - Mistry, Hitesh B

AU - Betts, Guy

AU - Cheadle, Eleanor J

AU - Dixon, Lynne

AU - Garcez, Kate

AU - Illidge, Tim

AU - Iyizoba-Ebozue, Zsuzsanna

AU - Lee, Lip Wai

AU - McPartlin, Andrew

AU - Prestwich, Robin J D

AU - Papageorgiou, Savvas

AU - Pritchard, Dylan J

AU - Sykes, Andrew

AU - West, Catharine M

AU - Thomson, David J

PY - 2022/4/6

Y1 - 2022/4/6

N2 - PURPOSE: There is a need to refine the selection of patients with oropharyngeal squamous cell carcinoma (OPSCC) for treatment de-escalation. We investigated whether pretreatment absolute lymphocyte count (ALC) predicted overall survival (OS) benefit from the addition of concurrent chemotherapy to radical radiotherapy.PATIENTS AND METHODS: This was an observational study of consecutive OPSCCs treated by curative-intent radiotherapy, with or without concurrent chemotherapy (n = 791) with external, independent validation from a separate institution (n = 609). The primary end point was OS at 5 years. Locoregional control (LRC) was assessed using competing risk regression as a secondary end point. Previously determined prognostic factors were used in a multivariable Cox proportional hazards model to assess the prognostic importance of ALC and the interaction between ALC and cisplatin chemotherapy use.RESULTS: Pretreatment ALC was prognostic for 5-year OS on multivariable analysis (hazard ratio [HR] 0.64; 95% CI, 0.42 to 0.98; P = .04). It also predicted benefit from the use of concurrent cisplatin chemotherapy, with a significant interaction between cisplatin chemotherapy and pretreatment ALC (likelihood ratio test, P = .04): higher ALC count reduced the 5-year OS benefit compared with radiotherapy alone (HR 2.53; 95% CI, 1.03 to 6.19; P = .043). This was likely driven by an effect on LRC up to 5 years (interaction subdistribution HR 2.29; 95% CI, 0.68 to 7.71; P = .094). An independent validation cohort replicated the OS (HR 2.53; 95% CI, 0.98 to 6.52; P = .055) and LRC findings (interaction subdistribution HR 3.43; 95% CI, 1.23 to 9.52; P = .018). CONCLUSION: For OPSCC, the pretreatment ALC is prognostic for OS and also predicts benefit from the addition of cisplatin chemotherapy to radiotherapy. These findings require prospective evaluation, and could inform the selection of good prognosis patients for a de-escalation trial.

AB - PURPOSE: There is a need to refine the selection of patients with oropharyngeal squamous cell carcinoma (OPSCC) for treatment de-escalation. We investigated whether pretreatment absolute lymphocyte count (ALC) predicted overall survival (OS) benefit from the addition of concurrent chemotherapy to radical radiotherapy.PATIENTS AND METHODS: This was an observational study of consecutive OPSCCs treated by curative-intent radiotherapy, with or without concurrent chemotherapy (n = 791) with external, independent validation from a separate institution (n = 609). The primary end point was OS at 5 years. Locoregional control (LRC) was assessed using competing risk regression as a secondary end point. Previously determined prognostic factors were used in a multivariable Cox proportional hazards model to assess the prognostic importance of ALC and the interaction between ALC and cisplatin chemotherapy use.RESULTS: Pretreatment ALC was prognostic for 5-year OS on multivariable analysis (hazard ratio [HR] 0.64; 95% CI, 0.42 to 0.98; P = .04). It also predicted benefit from the use of concurrent cisplatin chemotherapy, with a significant interaction between cisplatin chemotherapy and pretreatment ALC (likelihood ratio test, P = .04): higher ALC count reduced the 5-year OS benefit compared with radiotherapy alone (HR 2.53; 95% CI, 1.03 to 6.19; P = .043). This was likely driven by an effect on LRC up to 5 years (interaction subdistribution HR 2.29; 95% CI, 0.68 to 7.71; P = .094). An independent validation cohort replicated the OS (HR 2.53; 95% CI, 0.98 to 6.52; P = .055) and LRC findings (interaction subdistribution HR 3.43; 95% CI, 1.23 to 9.52; P = .018). CONCLUSION: For OPSCC, the pretreatment ALC is prognostic for OS and also predicts benefit from the addition of cisplatin chemotherapy to radiotherapy. These findings require prospective evaluation, and could inform the selection of good prognosis patients for a de-escalation trial.

U2 - 10.1200/JCO.21.01991

DO - 10.1200/JCO.21.01991

M3 - Article

C2 - 35385334

SN - 0732-183X

SP - JCO2101991

JO - Journal of clinical oncology : official journal of the American Society of Clinical Oncology

JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology

ER -

Pretreatment Lymphocyte Count Predicts Benefit From Concurrent Chemotherapy With Radiotherapy in Oropharyngeal Cancer

Abstract

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