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.

Impact of the peripheral blood inflammatory indices and modified nomogram-revised risk index on survival of Extranodal Nasal-Type Natural Killer/T-Cell lymphoma

“…In this study, albumin was associated with OS and PFS, and patients with lower albumin had a poor prognosis. Lymphocytes can strengthen the immune surveillance ability and suppress the proliferation, invasion, and metastasis of tumour cells and have been used to predict the prognosis of patients with many types of tumours, such as oropharyngeal cancer, melanoma, and skin cancer [ 21 , 22 , 23 , 24 ]. Serum monocyte levels can reflect the formation of tumour-associated macrophages (TAMs) in the tumour microenvironment [ 25 ].…”

Prognostic value of absolute lymphocyte count in oral cavity squamous cell carcinoma

“…The studies looking at predictivity of ALC in head and neck have been more discordant. When looking at oropharyngeal cancer, lower pretreatment ALC was prognostic for worse overall survival, but studies in nasopharyngeal carcinoma (NPC) showed that pretreatment ALC was not predictive marker for survival 12,13,18 . However, the NPC studies did show that treatment‐related lymphopenia, high NLR, and high platelet lymphocyte ratio (PLR) was associated with worse survival 12,13 …”

“…When looking at oropharyngeal cancer, lower pretreatment ALC was prognostic for worse overall survival, but studies in nasopharyngeal carcinoma (NPC) showed that pretreatment ALC was not predictive marker for survival. 12,13,18 However, the NPC studies did show that treatment-related lymphopenia, high NLR, and high platelet lymphocyte ratio (PLR) was associated with worse survival. 12,13 This study evaluates the prognostic value of pretreatment ALC in oral cavity cancers with regards to both recurrence and survival.…”

Predicting tumour radiosensitivity to deliver precision radiotherapy

“…In PACIFIC, patients derived a PFS benefit from the anti-PD-1 antibody durvalumab after chemoradiotherapy (HR 0.55, 95% CI 0.45-0.68), which was more pronounced in those with PD-L1-high tumours (HR 0.41, 95% CI 0.26-0.65) 146 . The pretreatment absolute lymphocyte count has prognostic value as a biomarker of immune function and also predicts for benefit from the addition of radiotherapy to chemotherapy in oropharyngeal carcinoma 151 and to immunotherapy in various solid tumour types 152 . Although this area of investigation is currently very active, at the time of writing none of the above immune biomarkers has been translated into clinical practice 153 .…”