Background: Incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rising rapidly in many western countries due to Human papillomavirus (HPV) and tobacco smoking, with a considerable overlap. Immunotherapy directed at the PD1/PD-L1 axis have shown promise in head and neck cancer and other cancer types. PD-L1 expression may indicate a poorer prognosis, and at the same time indicate a possible benefit of anti-PD-L1 immunotherapeutic agents. The primary aim of this study was to establish the prognostic effect of PD-L1 expression after primary curative radiotherapy alone. Material and methods: A cohort of 303 OPSCC patients treated with primary, curative intended radiotherapy was established. PD-L1 expression was evaluated by immunohistochemistry on formalin fixed, paraffin embedded tissue sections. PD-L1 positivity was defined as a Combined Positive Score (CPS) !1, indicating staining of either tumor cells, lymphocytes or macrophages. Results: Median follow-up was 5.3 years. With 199 deaths, there was no difference in overall survival between patients with PD-L1þ and PD-L1À tumors (adjusted hazard ratio [aHR] and 95% confidence interval [CI]: 1.0 [0.71-1.4]). Also, locoregional failure was similar between the two groups (aHR 1.1 [CI: 0.68 À 1.7]). Tumors were PD-L1þ in 76% of cases, significantly more among HPV p16þ tumors (82% vs. 70%, p ¼ .01). Interestingly, higher prevalence of PD-L1þ expression was seen in HPV p16þ patients with <10 pack-years of tobacco-smoking (93%) compared to HPV p16þ smokers (76%) or HPV p16-negative patients (70%) (p ¼ .003). Conclusion: PD-L1 expression had no prognostic significance in OPSCC patients treated with primary radiotherapy alone. A substantial proportion of OPSCC tumors show PD-L1 overexpression, especially in HPV p16þ tumors in patients with little or no smoking history.
PurposeSoft tissue sarcoma (STS) patients may experience post-treatment cardiotoxicity, yet no population-based data exist. We examined the incidence of left ventricular ejection fraction (LVEF) decline, heart failure, and cardiac death following STS diagnosis among adults, using Danish patient registries and medical record review.Patients and methodsLVEF decline was examined in a regional cohort of STS patients diagnosed during 1997–2011 in Western Denmark for whom cardiac imaging data were available. LVEF decline was defined as an absolute decline from baseline to follow-up of 10% or more, or, where baseline imaging was not available, a decline below the lower limit of normal (or 40%) for a follow-up LVEF. Heart failure and cardiac death were investigated in a national Danish cohort of all STS patients diagnosed from 2000 to 2009. We followed patients from STS diagnosis until heart failure, cardiac death, emigration or December 31, 2012 (whichever occurred first).ResultsThe incidence rate of LVEF decline for the regional cohort with follow-up data (N=100, five events) or baseline and follow-up measurements (N=75, 19 events) was 16.8 (95% confidence interval [CI]: 7.0–40.3) and 108 (95% CI: 69–170), respectively, per 1,000 person-years. In the national cohort (N=1,187), the incidence of heart failure (40 events) and cardiac death (15 events) was 7.3 (95% CI: 5.4–10.0) and 2.7 (95% CI: 1.6–4.5), respectively, per 1,000 person-years. The strongest predictors of heart failure were doxorubicin treatment (hazard ratio [HR] =2.2, 95% CI: 0.5–10.2) and pre-existing cardiovascular disease (HR=6.3, 95% CI: 0.98–40.6).ConclusionLVEF decline occurred more frequently compared to heart failure or cardiac death in a nationally representative cohort of Danish STS patients.
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