Department of Surgery, Section Surgical Oncology, Leiden University Medical Center, Leiden, The Netherlands,
Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
Gerontology. 2024;70(4):337-350. doi: 10.1159/000536471. Epub 2024 Jan 29.
Esophageal cancer is the seventh most common cancer worldwide and typically tends to manifest at an older age. Marked heterogeneity in time-dependent functional decline in older adults results in varying grades of clinically manifest patient fitness or frailty. The biological age-related adaptations that accompany functional decline have been shown to modulate the non-malignant cells comprising the tumor microenvironment (TME). In the current work, we studied the association between biological age and TME characteristics in patients with esophageal adenocarcinoma.
We comparatively assessed intratumoral histologic stroma quantity, tumor immune cell infiltrate, and blood leukocyte and thrombocyte count in 72 patients stratified over 3 strata of biological age (younger <70 years, fit older ≥70 years, and frail older adults ≥70 years), as defined by a geriatric assessment.
Frailty in older adults was predictive of decreased intratumoral stroma quantity (B = -14.66% stroma, p = 0.022) relative to tumors in chronological-age-matched fit older adults. Moreover, in comparison to younger adults, frail older adults (p = 0.032), but not fit older adults (p = 0.302), demonstrated a lower blood thrombocyte count at the time of diagnosis. Lastly, we found an increased proportion of tumors with a histologic desert TME histotype, comprising low stroma quantity and low immune cell infiltration, in frail older adults.
Our results illustrate the stromal-reprogramming effects of biological age and provide a biological underpinning for the clinical relevance of assessing frailty in patients with esophageal adenocarcinoma, further justifying the need for standardized geriatric assessment in geriatric cancer patients.
食管癌是全球第七大常见癌症，通常在老年时发病。老年人随时间推移的功能下降存在明显异质性，导致不同程度的临床明显患者体能或虚弱。伴随功能下降的生物学年龄相关适应性已被证明可调节构成肿瘤微环境（TME）的非恶性细胞。在目前的工作中，我们研究了生物学年龄与食管腺癌患者 TME 特征之间的关联。
我们比较评估了 72 名患者的肿瘤内组织学基质数量、肿瘤免疫细胞浸润以及白细胞和血小板计数，这些患者根据老年评估分为 3 个生物学年龄层（年轻<70 岁、体能较好的≥70 岁和虚弱的≥70 岁）。
与同龄体能较好的老年人相比，虚弱的老年人肿瘤内基质数量减少（B=-14.66%基质，p=0.022），这是衰老的预测指标。此外，与年轻人相比，虚弱的老年人（p=0.032）而不是体能较好的老年人（p=0.302）在诊断时血小板计数较低。最后，我们发现虚弱的老年人中存在更多具有组织学沙漠 TME 组织学类型的肿瘤，其特征是基质数量低和免疫细胞浸润低。
我们的结果说明了生物学年龄的基质重编程效应，并为评估食管腺癌患者虚弱的临床相关性提供了生物学基础，进一步证明了在老年癌症患者中进行标准化老年评估的必要性。
