Thomas Georgia, Weiss Elisabeth, Del Buono Marco Giuseppe, Moroni Francesco, West Josh, Myers Rachel, Kontos Emily, Golino Michele, Abbate Antonio, Canada Justin M
VCU Pauley Heart Center, Virginia Commonwealth University, 1200 East Broad Street, Richmond, VA, 23298, PO Box 980335, USA.
VCU Massey Cancer Center; Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA, USA.
Cardiooncology. 2024 Mar 12;10(1):15. doi: 10.1186/s40959-024-00216-2.
Contemporary radiotherapy for the treatment of lung cancer is effective in targeting tumor tissue while limiting heart exposure, yet cardiac toxicity still occurs, often becoming clinically apparent years later. Cardiorespiratory fitness (CRF) is an independent predictor of cardiovascular, cancer-related, and overall mortality and may serve as a sensitive measure of subclinical cardiac toxicity following anti-cancer treatments. Prior work has demonstrated a significant relationship between reduced CRF and impaired left-ventricular (LV) diastolic reserve in cancer survivors following thoracic radiotherapy. The purpose of this study was to assess early longitudinal changes in CRF and cardiac function in patients with lung cancer following radiotherapy.
Ten patients (69 [61-76] years, 70% female) with lung cancer without known cardiovascular disease scheduled to receive radiotherapy involving a clinically-relevant heart dose (≥ 5 Gy to > 10% of heart volume) were evaluated prior to and following treatment. Changes in CRF (peak oxygen consumption [VO], oxygen uptake efficiency slope [OUES]), cardiac function (LV ejection fraction [LVEF], rest and exercise diastolic function [diastolic functional reserve index (DFRI)]), cardiac biomarkers (N-terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity C-reactive protein [hsCRP]), and health-related quality of life (HRQOL; Functional Assessment of Cancer Therapy-General-7 [FACT-G7]) were measured.
The VO was reduced at baseline (1.245 [0.882-1.605] L·min; 70 [62-86] %-predicted) and significantly declined (1.095 [0.810-1.448] L·min, P = 0.047; 62 [56-76] %-predicted, P = 0.005) at 6.0 [3.0-6.0] months post-radiotherapy. Similarly, a significant decline in the OUES was observed (1.63 [1.27-1.88] to 1.57 [1.12-1.75], P = 0.032). Systolic cardiac function was normal at baseline and did not change following radiotherapy (LVEF; 62 [56-65]% to 66 [57-68]%, P = 0.475). The DFRI significantly declined following radiotherapy (34.9 [22.7-41.6] vs. 12.8 [3.1-35.9]). The hsCRP increased significantly from 4.4 [1.4-5.8] to 6.1 [3.7-20.7] g/L, P = 0.047 with a trend towards higher levels of NT-proBNP (65 [49-125] to 121 [88-191] pg/mL, P = 0.110). Health-related quality of life significantly decreased (FACT-G7; 21.5 [18.8-25] to 15.5 [11.5-20]; P = 0.021) post-radiotherapy.
Patients with lung cancer receiving radiotherapy with a clinically-significant heart dose experience reductions in CRF (VO, OUES) as early as six months following treatment with concurrent reductions in diastolic reserve (DFRI), HRQOL, and increases in cardiac biomarkers (NT-proBNP, hsCRP).
当代肺癌放射治疗在靶向肿瘤组织的同时能有效限制心脏受照剂量，但心脏毒性仍会发生，且往往在数年之后才在临床上显现出来。心肺适能（CRF）是心血管疾病、癌症相关死亡率及总死亡率的独立预测指标，可能作为抗癌治疗后亚临床心脏毒性的敏感指标。先前的研究表明，胸部放疗后的癌症幸存者中，CRF降低与左心室（LV）舒张储备受损之间存在显著关联。本研究的目的是评估肺癌患者放疗后CRF和心脏功能的早期纵向变化。
对10例（年龄69 [61 - 76]岁，70%为女性）无已知心血管疾病且计划接受涉及临床相关心脏剂量（≥5 Gy至＞10%心脏体积）放疗的肺癌患者在治疗前后进行评估。测量CRF（峰值摄氧量[VO]、摄氧效率斜率[OUES]）、心脏功能（左心室射血分数[LVEF]、静息和运动时舒张功能[舒张功能储备指数（DFRI）]）、心脏生物标志物（N末端脑钠肽前体[NT-proBNP]、高敏C反应蛋白[hsCRP]）以及健康相关生活质量（HRQOL；癌症治疗功能评估通用版7 [FACT-G7]）的变化。
VO在基线时降低（1.245 [0.882 - 1.6,05] L·min；预测值的70 [62 - 86]%），在放疗后6.0 [3.0 - 6.0]个月时显著下降（1.095 [0.810 - 1.448] L·min，P = 0.047；预测值的62 [56 - 76]%，P = 0.005）。同样，观察到OUES显著下降（从1.63 [1.27 - 1.88]降至1.57 [1.12 - 1.75]，P = 0.032）。收缩期心脏功能在基线时正常，放疗后无变化（LVEF；从62 [56 - 65]%至66 [57 - 68]%，P = 0.475）。放疗后DFRI显著下降（34.9 [22.7 - 41.6]对vs对12.8 [3.1 - 35.9]）。hsCRP从4.4 [1.4 - 5.8]显著升高至6.1 [3.7 - 20.7] g/L，P = 0.047，NT-proBNP有升高趋势（从65 [49 - 125]至121 [88 - 191] pg/mL，P = 0.110）。放疗后健康相关生活质量显著下降（FACT-G7；从21.5 [18.8 - 25]降至15.5 [11.5 - 20]；P = 0.021）。
接受具有临床显著心脏剂量放疗的肺癌患者在治疗后6个月时CRF（VO、OUES）即出现下降，同时舒张储备（DFRI）降低、HRQOL下降以及心脏生物标志物（NT-proBNP、hsCRP）升高。
