Predictors of Liver Toxicity Following Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma.

PURPOSE: To identify risk factors associated with a decline in liver function after stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma. METHODS AND MATERIALS: Data were analyzed from patients with hepatocellular carcinoma treated on clinical trials of 6-fraction SBRT. Liver toxicity was defined as an increase in Child-Pugh (CP) score ≥2 three months after SBRT. Clinical factors, SBRT details, and liver dose-volume histogram (DVH) parameters were tested for association with toxicity using logistic regression. CP class B patients were analyzed separately. RESULTS: Among CP class A patients, 101 were evaluable, with a baseline score of A5 (72%) or A6 (28%). Fifty-three percent had portal vein thrombus. The median liver volume was 1286 cc (range, 766-3967 cc), and the median prescribed dose was 36 Gy (range, 27-54 Gy). Toxicity was seen in 26 patients (26%). Thrombus, baseline CP of A6, and lower platelet count were associated with toxicity on univariate analysis, as were several liver DVH-based parameters. Absolute and spared liver volumes were not significant. On multivariate analysis for CP class A patients, significant associations were found for baseline CP score of A6 (odds ratio [OR], 4.85), lower platelet count (OR, 0.90; median, 108 × 109/L vs 150 × 109/L), higher mean liver dose (OR, 1.33; median, 16.9 Gy vs 14.7 Gy), and higher dose to 800 cc of liver (OR, 1.11; median, 14.3 Gy vs 6.0 Gy). With 13 CP-B7 patients included or when dose to 800 cc of liver was replaced with other DVH parameters (eg, dose to 700 or 900 cc of liver) in the multivariate analysis, effective volume and portal vein thrombus were associated with an increased risk. CONCLUSIONS: Baseline CP scores and higher liver doses (eg, mean dose, effective volume, doses to 700-900 cc) were strongly associated with liver function decline 3 months after SBRT. A lower baseline platelet count and portal vein thrombus were also associated with an increased risk.

Systemic inflammation is an independent predictive marker of clinical outcomes in mucosal squamous cell carcinoma of the head and neck in oropharyngeal and non-oropharyngeal patients.

BACKGROUND: Currently there are very few biomarkers to identify head and neck squamous cell carcinoma (HNSCC) cancer patients at a greater risk of recurrence and shortened survival. This study aimed to investigate whether a marker of systemic inflammation, the neutrophil-to-lymphocyte ratio (NLR), was predictive of clinical outcomes in a heterogeneous cohort of HNSCC cancer patients. METHODS: We performed a retrospective analysis to identify associations between NLR and clinicopathological features to recurrence free survival (RFS) and overall survival (OS). Univariate analysis was used to identify associations and selected variables were included in multivariable Cox regression analysis to determine predictive value. RESULTS: A total of 145 patients with stage I-IV HNSCC that had undergone radiotherapy were analysed. Seventy-six of these patients had oropharyngeal cancer and 69 had non-oropharyngeal HNSCC and these populations were analysed separately. NLR was not associated to any clinicopathological variable. On univariate analysis, NLR showed associations with RFS and OS in both sub-populations. Multivariable analysis showed patients with NLR > 5 had shortened OS in both sub-populations but NLR > 5 only predicted RFS in oropharyngeal patients. Poor performance status predicted OS in both sub-populations and current smokers had shortened OS and RFS in non-oropharyngeal patients. CONCLUSIONS: The results show patients with NLR > 5 predict for shorter overall survival. Further prospective validation studies in larger cohorts are required to determine the clinical applicability of NLR for prognostication in HNSCC patients.

Neutrophil-to-lymphocyte ratio in head and neck cancer.

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) is an index of systemic inflammatory burden in malignancy. An elevated NLR has been associated with poor prognosis in a number of cancer sites. We investigated its role in a cohort of patients with locally advanced head and neck cancer. METHODS: Eligible patients had primary mucosal squamous cell carcinoma treated with chemoradiotherapy and a minimum follow-up of 12 months (unless deceased). NLR was analysed as <5 vs. ≥5 and above and below the median. The primary endpoint was overall survival (OS) and secondary endpoints metastasis free survival and locoregional relapse free survival. Actuarial Kaplan-Meier statistics and log rank test were used. Univariate analysis for age (continuous), Eastern Cooperative Oncology Group performance status (0 vs. 1), gender (male vs. female), smoking (yes vs. no), American Joint Committee on Cancer stage (III vs. IV) and NLR (<5 vs. ≥5 and <3.3 vs. ≥3.3) were performed. RESULTS: Forty-six patients were included in this analysis. Median NLR was 3.3 (0.4-22.8). After a median follow-up of 34 months (13-47 months), the 2-year estimated OS, metastasis free survival and locoregional relapse free survival for NLR <5 vs. ≥5 were 89% vs. 61% (p = 0.017), 84% vs. 64% (p = 0.083) and 81% vs. 70% (p = 0.17) respectively. On univariate analysis NLR ≥5 (p = 0.025), older age (p = 0.01) and ECOG 1 (p = 0.025) were significant for OS. CONCLUSION: In this cohort of locally advanced head and neck cancer patients treated with chemoradiotherapy, pre-treatment NLR ≥5 was prognostic for mortality. Further studies are required to confirm these results and to assess the interaction with other prognostic factors.

Outcomes following definitive stereotactic body radiotherapy for patients with Child-Pugh B or C hepatocellular carcinoma.

PURPOSE: To report outcomes in patients with Child-Pugh B or C (CP B/C) hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: A prospective study of SBRT was developed for patients with CP B7 or B8 unresectable HCC, <10 cm. Selected ineligible patients (e.g. CP>B8, >10 cm) treated off-study from 2004 to July 2012 were also reviewed. Patients were excluded if they were treated as a bridge-to-liver-transplant. RESULTS: 29 patients with CP B/C HCC were treated with SBRT (median dose 30 Gy in 6 fractions) from 2004 to December 2012. The majority had CP B7 liver function (69%) and portal vein tumor thrombosis (76%). The median survival was 7.9 months (95% CI: 2.8-15.1). Survival was significantly better in patients with CP=B7 and AFP≤4491 ng/mL. Of 16 evaluable patients, 63% had a decline in CP score by ≥2 points at 3 months. CONCLUSION: SBRT is a treatment option for selected HCC patients with small HCCs and modestly impaired (CP B7) liver function.