Prognostic significance of neutrophil‐to‐lymphocyte ratio in HPV status era for oropharyngeal cancer

Fanetti, Giuseppe; Alterio, Daniela; Marvaso, Giulia; Gandini, Sara; Rojas, Damaris Patricia; Gobitti, Carlo; Minatel, Emilio; Revelant, Alberto; Caroli, Angela; Francia, C.; Alessandro, Ombretta; Pepa, Matteo; Gugliandolo, Simone Giovanni; Starzyńska, Anna; Polesel, Jerry; Vaccher, Emanuela; Rocca, Maria Cossu; Tagliabue, Marta; Ansarin, Mohssen; Lupato, Valentina; Giacomarra, Vittorio; Paoli, Antonino De; Orecchia, Roberto; Franchin, Giovanni; Jereczek‐Fossa, Barbara Alicja

doi:10.1111/odi.13366

Cited by 18 publications

(21 citation statements)

References 36 publications

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“…Three other studies assessing the NLR reported prognostic significance, but dichotomized NLR values solely on the sample median. [29][30][31] Furthermore, in two studies, event rates were low and CIs were large, 30,31 and in the other, 45% of patients received induction chemotherapy, potentially confounding results. 29 Strengths of our study were the larger sample size, including discovery and validation cohorts, excluding cases treated with induction chemotherapy, and analyzing ALC as a continuous variable.…”

Section: Discussionmentioning

confidence: 96%

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

Price

Mistry

Betts

et al. 2022

JCO

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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.

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Section: Discussionmentioning

confidence: 96%

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

Price

Mistry

Betts

et al. 2022

JCO

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“…As a consequence, unlike other studies reporting an association between a high NLR and poor outcome in HNSCC 2 and laryngeal cancer, 21 this ratio was not associated with outcome in the present series. However, other authors have failed to identify an association between preoperative NLR and DFS both in laryngeal 22 and oropharyngeal SCC 23 . Interestingly, in a series of patients with HNSCC, it was observed that the prognostic capability of NLR mostly depended on the number of neutrophils with the lymphocytes contributing limitedly 2 .…”

Section: Discussionmentioning

confidence: 97%

“…However, other authors have failed to identify an association between preoperative NLR and DFS both in laryngeal 22 and oropharyngeal SCC. 23 Interestingly, in a series of patients with HNSCC, it was observed that the prognostic capability of NLR mostly depended on the number of neutrophils with the lymphocytes contributing limitedly. 2 In this regard, it should also be considered that use of steroids is more frequent in laryngeal cancer, to reduce oedema and improve breathing, and possibly associated with a transient increase in neutrophil count.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of H‐index in patients surgically treated for squamous cell carcinoma of the larynx

Boscolo‐Rizzo

Zanelli

Giudici

et al. 2021

Laryngoscope Investig Oto

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Objective Recently, a novel host‐related index, the Host‐index (H‐index), including both inflammatory and nutritional markers, has been described and observed to stratify prognosis in patients with squamous cell carcinoma (SCC) of the oral cavity more accurately than other host‐related indexes This study aimed to investigate the prognostic performance of the H‐index using pretreatment blood tests in patients receiving up‐front surgery for SCC of the larynx. Methods This retrospective observational study included a multicenter series of consecutive patients with SCC of the larynx diagnosed between 1 January 2009 and 31 July 2018, whose pretreatment blood tests were available and included the parameters necessary for the calculation of neutrophil to lymphocyte ratio (NLR) and the H‐index. Their association with disease‐free survival (DFS) and overall survival (OS) was measured. Results A total of 231 patients were eligible for the present analysis (median [range] age, 68 [37‐96] years; 191 [82.7%] men). The median follow‐up was 73 months. In multivariable Cox proportional hazards regression models, increasing age (adjusted hazard ratio [aHR], 1.07 per year; 95% CI, 1.04‐1.09), advanced pT stage (aHR = 1.71 95% CI: 1.07‐2.71), and having close or positive surgical margins (aHR = 2.01; 95% CI: 1.21‐3.33) were significantly associated with poor OS. Among blood parameters, a higher neutrophil count was a strong predictor of both worse DFS (aHR for recurrence/death = 2.34; 95% CI: 1.24‐4.40) and OS (aHR for death = 2.67; 95% CI: 1.51‐4.71). Among inflammatory blood indexes, while NLR was not significantly associated with DFS or OS, patients with H‐index ≥8.37 showed a higher aHR for both recurrence/death (2.82; 95% CI: 1.65‐4.79) and death (2.22; 95% CI: 1.26‐3.89). Conclusion In conclusion, the present study confirms the prognostic value of pretreatment H‐index, an easily measurable inflammatory and nutritional index, in patients with SCC of the larynx. Level of Evidence III

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“…The ratio of circulating peripheral blood neutrophils in relation to lymphocytes has been suggested as a potential prognostic marker for many cancers including OPSCC [ 43 , 44 ]. A high circulating neutrophil to lymphocyte ratio (NLR) has been found for both HPV-positive and HPV-negative OPSCC [ 45 ]. In HPV-positive OPSCC, a high NLR was associated with higher T classification, lower 5-year overall survival and disease-free survival [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Increased Abundance of Tumour-Associated Neutrophils in HPV-Negative Compared to HPV-Positive Oropharyngeal Squamous Cell Carcinoma Is Mediated by IL-1R Signalling

Al-Sahaf

Hendawi

Ollington

et al. 2021

Front. Oral. Health

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The incidence of human papillomavirus (HPV)-associated cancer is increasing and HPV is now implicated in the aetiology of more than 60% of all oropharyngeal squamous cell carcinomas (OPSCC). In OPSCC, innate immune cells such as neutrophils and macrophages generally correlate with poor prognosis, whilst adaptive immune cells, such as lymphocytes, tend to correlate with improved prognosis. This may, in part, be due to differences in the immune response within the tumour microenvironment leading to the recruitment of specific tumour-associated leukocyte sub-populations. In this study, we aimed to examine if differences exist in the levels of infiltrated leukocyte sub-populations, with particular emphasis on tumour-associated neutrophils (TAN), and to determine the mechanism of chemokine-induced leukocyte recruitment in HPV-positive compared to HPV-negative OPSCC. Immunohistochemical analysis showed that HPV-negative OPSCC contained significantly more neutrophils than HPV-positive tumours, whilst levels of CD68+ macrophages and CD3+ lymphocytes were similar. Using a 3D tissue culture model to represent tumour-stromal interactions, we demonstrated that HPV-negative tumour-stromal co-cultures expressed significantly higher levels of CXCL8, leading to increased neutrophil recruitment compared to their HPV-positive counterparts. HPV-negative OPSCC cells have previously been shown to express higher levels of IL-1 than their HPV-positive counterparts, indicating that this cytokine may be responsible for driving increased chemokine production in the HPV-negative 3D model. Inhibition of IL-1R in the tumour-stromal models using the receptor-specific antagonist, anakinra, dramatically reduced chemokine secretion and significantly impaired neutrophil and monocyte recruitment, suggesting that this tumour-stromal response is mediated by the IL-1/IL-1R axis. Here, we identify a mechanism by which HPV-negative OPSCC may recruit more TAN than HPV-positive OPSCC. Since TAN are associated with poor prognosis in OPSCC, our study identifies potential therapeutic targets aimed at redressing the chemokine imbalance to reduce innate immune cell infiltration with the aim of improving patient outcome.

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Prognostic significance of neutrophil‐to‐lymphocyte ratio in HPV status era for oropharyngeal cancer

Cited by 18 publications

References 36 publications

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

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

Prognostic value of H‐index in patients surgically treated for squamous cell carcinoma of the larynx

Increased Abundance of Tumour-Associated Neutrophils in HPV-Negative Compared to HPV-Positive Oropharyngeal Squamous Cell Carcinoma Is Mediated by IL-1R Signalling

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