A Systematic Review of Radiation-Related Lymphopenia in Genito-urinary Malignancies

The impact of radiation-related lymphopenia on clinical outcomes has been reported in various solid malignancies such as high grade gliomas, head and neck cancers, thoracic malignancies and gastro-intestinal malignancies but its impact is not clearly known in the context of common genito-urinary (GU) malignancies. To better understand the effect of radiation-associated lymphopenia in prostate and bladder cancer, we undertook this systematic review of clinical studies that have studied radiation-related lymphopenia in GU malignancies. A systematic methodology search of PubMed, Embase, and Cochrane library resulted in 2125 abstracts. Ten studies fulfilled the inclusion criteria which included any prospective, retrospective study or cohort study of prostate, urinary bladder, kidney, ureter, urethra, penile cancer in humans, and radiation should be part of treatment and intent has to be in definitive or adjuvant settings. Finally the study should have data on radiation-related lymphopenia. Four studies reported on the cancer-specific outcomes related to the lymphopenia. The incidence of low lymphocyte counts were documented in all the studies. Three studies analyzed the factors associated with the Lymphocyte depletion. Pooled incidence of severe lymphopenia was 29.25% and mild to moderate lymphopenia was 60.75%. Bone marrow volume receiving 40 Gy was associated with the incidence of lymphopenia. One-third of the patients suffer from severe lymphopenia after radiation in prostate and bladder cancer. There are no clear data to support the correlation between severe lymphopenia and disease outcomes. Bone marrow dosimetry can affect the incidence and severity of lymphopenia. There is need of prospective datasets to identify the impact of radiation-related lymphopenia in GU malignancies focusing on long-term side effects, recurrence rates, and overall survival.

放疗相关淋巴细胞减少症（radiation-related lymphopenia）对临床结局的影响，已在高级别胶质瘤（high grade gliomas）、头颈部恶性肿瘤、胸部恶性肿瘤（thoracic malignancies）及胃肠道恶性肿瘤（gastro-intestinal malignancies）等多种实体恶性肿瘤（solid malignancies）中被报道，但在常见泌尿生殖系统（genito-urinary, GU）恶性肿瘤的相关研究中，其影响尚不明确。为明确放疗相关淋巴细胞减少症在前列腺癌与膀胱癌中的作用，我们针对泌尿生殖系统恶性肿瘤中放疗相关淋巴细胞减少症的临床研究开展了本次系统综述。通过对PubMed、Embase及Cochrane图书馆进行系统性方法学检索，共检索得到2125篇摘要。最终有10项研究符合纳入标准：纳入标准涵盖针对人类前列腺癌、膀胱癌、肾癌、输尿管癌、尿道癌及阴茎癌开展的前瞻性研究、回顾性研究或队列研究，且放疗需作为治疗方案的一部分，治疗意图需为根治性或辅助性治疗，且研究需包含放疗相关淋巴细胞减少症相关数据。其中4项研究报道了与淋巴细胞减少相关的肿瘤特异性结局，所有研究均记录了淋巴细胞计数降低的发生率，另有3项研究分析了淋巴细胞耗竭的相关影响因素。严重淋巴细胞减少症的合并发生率为29.25%，轻至中度淋巴细胞减少症的合并发生率为60.75%。受照剂量达40戈瑞（Gy）的骨髓体积与淋巴细胞减少症的发生相关。在前列腺癌与膀胱癌患者中，有三分之一的患者在放疗后出现严重淋巴细胞减少症。目前尚无明确数据证实严重淋巴细胞减少症与疾病结局之间存在相关性。骨髓剂量学可影响淋巴细胞减少症的发生率与严重程度。未来仍需开展前瞻性研究数据集，以明确泌尿生殖系统恶性肿瘤中放疗相关淋巴细胞减少症的影响，重点关注其长期不良反应、复发率及总生存期。