Leukocytosis and neutrophilia predicts outcome in anal cancer

Schernberg, Antoine; Escande, Alexandre; Campo, Eleonor Rivin del; Ducreux, Michel; Goèré, Diane; Chargari, Cyrus; Deutsch, Éric

doi:10.1016/j.radonc.2016.12.009

Cited by 53 publications

(68 citation statements)

References 32 publications

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“…Also, a combined leukocyte-CEA score revealed that classified patients into three risk groups showed strong correlation with clinical outcome. Our data are in line to previous reports indicating an unfavorable role of peripheral blood leukocytosis and neutrophilia in the context of inflammation in different malignancies, [12][13][14][15][16][17][18]21 including rectal cancer. 22,23 With regard to NLR, a pooled analysis of retrospective studies indicated a negative predictive impact in rectal cancer.…”

Section: <0001supporting

confidence: 93%

“…11 Although several groups have reported the unfavorable prognostic impact of peripheral blood leukocytosis and/or neutrophilia in patients with various malignancies, also in the context of neutrophil-to-lymphocyte ratio (NLR), these studies were limited by their retrospective nature, inhomogeneous treatment regimens and small patient numbers. [12][13][14][15][16][17][18] In the present secondary analysis, we examined the prognostic role of peripheral blood leukocytes and neutrophils together with other markers, including hemoglobin, platelets, lactate dehydrogenase (LDH) and carcinoembryonic antigen (CEA), in a large cohort of patients with rectal cancer (n = 1,236) treated within the CAO/ARO/AIO-04 phase 3 randomized trial. 19 In that trial, the addition of oxaliplatin to 5-FU-based preoperative CRT resulted in a significant improvement of the primary endpoint, DFS, compared to the standard arm.…”

Section: Introductionmentioning

confidence: 99%

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Leukocytosis and neutrophilia as independent prognostic immunological biomarkers for clinical outcome in the CAO/ARO/AIO‐04 randomized phase 3 rectal cancer trial

Diefenhardt

Hofheinz

Martin

et al. 2019

Intl Journal of Cancer

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Peripheral blood leukocytosis and neutrophilia reflect cancer inflammation and have been proposed as prognostic immunological biomarkers in various malignancies. However, previous studies were limited by their retrospective nature and small patient numbers. Baseline peripheral blood leukocytes, neutrophils, hemoglobin, platelets, lactate dehydrogenase and carcinoembryonic antigen (CEA) were correlated with clinicopathologic characteristics, and clinical outcome in 1236 patients with rectal cancer treated with 5‐FU‐based preoperative chemoradiotherapy (CRT) alone or with oxaliplatin followed by surgery and adjuvant chemotherapy within the CAO/ARO/AIO‐04 randomized phase 3 trial. Multivariable analyses were performed using Cox regression models. After a median follow‐up of 50 months, baseline leukocytosis remained an independent adverse prognostic factor for disease‐free survival (DFS; HR 1.457; 95% CI 1.163–1.825; p = 0.001), distant metastasis (HR 1.696; 95% CI 1.266–2.273; p < 0.001) and overall survival (OS; HR 1.716; 95% CI 1.264–2.329; p = 0.001) in multivariable analysis. Similar significant findings were observed for neutrophilia and high CEA levels. Conversely, treatment‐induced leukopenia correlated with favorable DFS (p = 0.037), distant metastasis (p = 0.028) and OS (p = 0.012). Intriguingly, addition of oxaliplatin to 5‐FU CRT resulted in a significant DFS improvement only in patients with neutrophilia and leukocytosis (p = 0.028 and p = 0.002). Our findings have important clinical implications and provide high‐level evidence on the adverse prognostic role of leukocytes and neutrophils, and the impact of chemotherapy in the context of these biomarkers. These data could help guide patient stratification and should be further validated within prospective studies.

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Section: <0001supporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Leukocytosis and neutrophilia as independent prognostic immunological biomarkers for clinical outcome in the CAO/ARO/AIO‐04 randomized phase 3 rectal cancer trial

Diefenhardt

Hofheinz

Martin

et al. 2019

Intl Journal of Cancer

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“…Laboratory findings of patients were examined more than 2 times prior to treatment without any evidence of infection (Cho et al, ). TRL was defined as at least 2 separated occasions of leukocytosis exceeding number of white blood cell count>10,000/μl without any evidence of infection (Mabuchi et al, ; Schernberg, Escande, et al, ). The neutrophil–lymphocyte ratio was defined as the absolute neutrophil count divided by the absolute lymphocyte count.…”

Section: Methodsmentioning

confidence: 99%

“…Clinical characteristics of patients were reviewed, including age at diagnosis (>60 years old), sex, history of smoking (≥20 pack‐years), alcohol consumption (≥1 drink/day), Karnofsky performance status (≤80), Charlson's comorbidity index (Etienne et al, ), tumor site and extent and gross node and extranodal extension involvement, and postoperative treatment. The reference limits of baseline biomarkers in laboratory findings were defined from previous reports and our institutional normal ranges as TRL (white blood cell count > 10,000/μl; Mabuchi et al, ; Schernberg, Escande, et al, ), anemia (<11 g/dl in both genders) (Holgersson et al, ), hypoalbuminemia (<3.5 g/dl; Park, Kim, et al, ; Park, Roh, et al, ), hypoproteinemia (<6.0 g/dl; Park, Roh, et al, ), neutrophilia (>7,500/μl; Schernberg, Escande, et al, ), lymphocytopenia (<1,000/μl; Schernberg, Moureau‐Zabotto, et al, ), monocytosis (>1,000/μl; Schernberg, Moureau‐Zabotto, et al, ), thrombophilia (>350 × 10 3 /μl; Holgersson et al, ; Schernberg, Moureau‐Zabotto, et al, ), neutrophil–lymphocyte ratio (>2.5) (Cho et al, ), platelet–lymphocyte ratio (>200) (Park, Roh, et al, ), and monocyte–lymphocyte ratio (>0.5) (Cho et al, ). Pathological factors of patients included tumor site (others/oral tongue) and extent, size (≤2/2.1–4/>4 cm) (Amin et al, ; Edge et al, ), invasion depth (≤5/5.1–10/>10 cm; Amin et al, ), differentiation (well/moderately/poorly), perineural and lymphovascular invasion (Geweiler, Inhestern, Berndt, & Guntinas‐Lichius, ), and resection margins (involved).…”

Section: Methodsmentioning

confidence: 99%

“…Abnormally increased numbers of white blood cells in circulating blood, diagnosed as tumor-related leukocytosis (TRL), are associated with poor therapeutic response and survival outcomes in patients with solid tumors (Granger & Kontoyiannis, 2009). TRL caused by the overexpression of hematological growth factors displays an aggressive feature resistant to radiotherapy or chemoradiotherapy among patients with uterine cervical (Cho, Kim, Yoon, Kim, & Kim, 2016), anal (Schernberg, Escande, et al, 2017a), esophageal (Schernberg, Moureau-Zabotto, et al, 2017b), or non-small-cell lung cancer (Holgersson et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Tumor‐related leukocytosis predictive of recurrence and survival in patients with oral cavity squamous cell carcinoma

et al. 2019

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Objective To evaluate the prognostic values of tumor‐related leukocytosis (TRL) as a reliable biomarker predictive of recurrence and survival after definitive surgery for oral cavity squamous cell carcinoma (OSCC). Materials and methods This retrospective study involved 322 patients who underwent tumor extirpation combined with neck dissection for treatment‐naïve OSCC between 2006 and 2014. Multivariate binary logistic regression analyses were used to analyze the relationship between TRL and pathological variables. Cox proportional hazard regression analyses were used to find associations between factors and disease‐free survival (DFS) or overall survival (OS). Results TRL was significantly related to advanced disease status, tumor size, invasion depth, poor differentiation, and T and N classifications, resulting in increased post‐treatment recurrence rate, particularly in the distant site. Multivariate logistic regression analyses showed that only the T classification was significantly associated with baseline TRL (p = 0.018). Multivariate analyses also showed that the tumor depth of invasion, pathological N classification, extranodal extension, and TRL remained the independent variables predictive of DFS and OS (all p < 0.05). TRL was related to a more than twofold increased risk of post‐treatment recurrence and mortality. Conclusions TRL is associated with advanced tumor disease and increased recurrence and mortality in OSCC patients.

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Prediction of pharyngocutaneous fistula and survival after salvage laryngectomy for laryngohypopharyngeal carcinoma

et al. 2019

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Background This study examined the risk factors of pharyngocutaneous fistula development and poor survival after salvage laryngectomy. Methods Binary logistic regression analyses were carried out to analyze the relationship between post‐salvage fistula development and variables. Univariate and multivariate Cox proportional hazard regression analyses were performed to evaluate prognostic factors associated with disease‐free survival (DFS) and overall survival (OS) after salvage laryngectomy. Results Multivariate analyses showed that previous radiotherapy and pre‐salvage tracheostomy were the independent variables predictive of post‐salvage fistula development (all P < .05). The 5‐year DFS and OS rates were 58.8% and 45.9%, respectively. Multivariate analyses showed that nodal positivity at salvage remained the independent factor predictive of both DFS (hazard ratio [HR] 2.83, P = .002) and OS (HR 2.22, P = .006). Conclusions Fistula development after salvage laryngectomy might be predicted by a history of radiotherapy or tracheostomy. Post‐salvage survival is associated with nodal positivity at salvage. Condensed Abstract This study examined the risk factors of pharyngocutaneous fistula development and survival in 103 patients who underwent salvage laryngectomy. Previous radiotherapy and tracheostomy were the independent variables predictive of post‐salvage fistula development, and nodal positivity at salvage was the independent factor predictive of both disease‐free survival and overall survival.

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Leukocytosis and neutrophilia predicts outcome in anal cancer

Cited by 53 publications

References 32 publications

Leukocytosis and neutrophilia as independent prognostic immunological biomarkers for clinical outcome in the CAO/ARO/AIO‐04 randomized phase 3 rectal cancer trial

Leukocytosis and neutrophilia as independent prognostic immunological biomarkers for clinical outcome in the CAO/ARO/AIO‐04 randomized phase 3 rectal cancer trial

Tumor‐related leukocytosis predictive of recurrence and survival in patients with oral cavity squamous cell carcinoma

Prediction of pharyngocutaneous fistula and survival after salvage laryngectomy for laryngohypopharyngeal carcinoma

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