放疗早期循环淋巴细胞计数与小儿髓母细胞瘤复发相关。
Circulating Lymphocyte Counts Early During Radiation Therapy Are Associated With Recurrence in Pediatric Medulloblastoma.
机构信息
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
出版信息
Int J Radiat Oncol Biol Phys. 2021 Jul 15;110(4):1044-1052. doi: 10.1016/j.ijrobp.2021.01.035. Epub 2021 Feb 5.
PURPOSE
Decreased peripheral lymphocyte counts are associated with survival after radiation therapy (RT) in several solid tumors, although they appear late during or after the radiation course and often correlate with other clinical factors. Here we investigate if absolute lymphocyte counts (ALCs) are independently associated with recurrence in pediatric medulloblastoma early during RT.
METHODS AND MATERIALS
We assessed 202 patients with medulloblastoma treated between 2000 and 2016 and analyzed ALC throughout therapy, focusing on both early markers (ALC during week 1 - ALC; grade 3+ Lymphopenia during week 2 - Lymphopenia) and late markers (ALC nadir). Uni- and multivariable regressions were used to assess association of clinical and treatment variables with ALC and of ALC with recurrence.
RESULTS
Thirty-six recurrences were observed, with a median time to recurrence of 1.6 years (range, 0.2-10.3) and 7.1 years median follow-up. ALC during RT was associated with induction chemotherapy (P < .001), concurrent carboplatin (P = .009), age (P = .01), and high-risk status (P = .05). On univariable analysis, high-risk disease (hazard ratio = 2.0 [1.06-3.9]; P = .03) and M stage≥1 (hazard ratio = 2.2 [1.1-4.4]) were associated with recurrence risk, as was lower ALC early during RT (ALC, hazard ratio = 0.28 [0.12-0.65]; P = .003; Lymphopenia, hazard ratio = 2.27 [1.1-4.6]; P = .02). Neither baseline ALC nor nadir correlated with outcome. These associations persisted when excluding carboplatin and pre-RT chemotherapy patients, and in the multivariable analysis accounting for confounders lymphocyte counts remained significant (ALC, hazard-ratio = 0.23 [0.09-0.57]; P = .002; Lymphopenia, hazard-ratio = 2.3 [1.1-4.8]; P = .03).
CONCLUSIONS
ALC during weeks 1 and 2 of RT was associated with recurrence, and low ALC is an independent prognostic factor in medulloblastoma. Strategies to mitigate the risk of radiation-induced lymphopenia should be considered.
目的
在几种实体瘤中，外周淋巴细胞计数减少与放射治疗（RT）后的生存相关，尽管它们在放射治疗过程中或之后晚期出现，且常与其他临床因素相关。在此，我们研究了在 RT 早期，绝对淋巴细胞计数（ALC）是否与小儿髓母细胞瘤的复发独立相关。
方法和材料
我们评估了 202 例 2000 年至 2016 年间接受治疗的髓母细胞瘤患者，并分析了整个治疗过程中的 ALC，重点关注早期标志物（第 1 周的 ALC-ALC；第 2 周的 3 级+淋巴细胞减少症-淋巴细胞减少症）和晚期标志物（ALC 最低点）。采用单变量和多变量回归来评估临床和治疗变量与 ALC 的关系，以及 ALC 与复发的关系。
结果
观察到 36 例复发，中位复发时间为 1.6 年（范围为 0.2-10.3），中位随访时间为 7.1 年。RT 期间的 ALC 与诱导化疗（P<0.001）、同期卡铂（P=0.009）、年龄（P=0.01）和高危状态（P=0.05）相关。单变量分析显示，高危疾病（危险比=2.0[1.06-3.9]；P=0.03）和 M 期≥1（危险比=2.2[1.1-4.4]）与复发风险相关，RT 早期的 ALC 较低也与复发风险相关（ALC，危险比=0.28[0.12-0.65]；P=0.003；淋巴细胞减少症，危险比=2.27[1.1-4.6]；P=0.02）。基线 ALC 或最低点均与结局无关。当排除卡铂和 RT 前化疗患者时，这些关联仍然存在，且在多变量分析中，考虑混杂因素后，淋巴细胞计数仍具有显著性（ALC，危险比=0.23[0.09-0.57]；P=0.002；淋巴细胞减少症，危险比=2.3[1.1-4.8]；P=0.03）。
结论
RT 第 1 周和第 2 周的 ALC 与复发相关，低 ALC 是髓母细胞瘤的独立预后因素。应考虑减轻放疗引起的淋巴细胞减少症风险的策略。
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