Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
Department of Gastrointestinal Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
World J Surg Oncol. 2021 Nov 15;19(1):324. doi: 10.1186/s12957-021-02441-w.
In the Response Evaluation Criteria for Solid Tumors (RECIST) diagnostic criteria, the concepts of progression by preexisting disease (PPL) and progression by new metastases (PNM) have been proposed to distinguish between the progression types of cancer refractory to treatment. According to the tumor biology of cancer progression forms, the "PPL" form indicates invasion, and the "PNM" form indicates metastasis. On the other hand, recent studies have focused on the clinical importance of inflammatory markers as indicators of the systemic tumor immune response. In particular, absolute lymphocyte count (ALC) is an indicator of the host's immune response. Thus, we developed a new measure that combined progression form with ALC. In this study, we clinically validated the combined assessment of progression form and ALC in eribulin chemotherapy.
From August 2011 to April 2019, a total of 486 patients with locally advanced or metastatic breast cancer (MBC) underwent treatment. In this study, only 88 patients who underwent chemotherapy using eribulin were included. The antitumor effect was evaluated based on the RECIST criteria, version 1.1. To measure ALC, peripheral blood samples collected before eribulin treatment were used. The cut-off value for ALC in this study was 1500/μl, based on previous studies.
The PPL group (71 patients, 80.7%) had significantly longer progression-free survival (PFS) (p = 0.022, log-rank) and overall survival (OS) (p < 0.001, log-rank) than the PNM group (17 patients, 19.3%). In the 51 patients with ALC < 1500/μl, the PPL group had a significantly better prognosis than the PNM group (PFS: p = 0.035, OS: p < 0.001, log-rank, respectively). On the other hand, in the 37 patients with ALC ≥ 1500/μl, the PPL group had a better OS compared with the PNM group (p = 0.055, log-rank), but there was no significant difference in PFS between the two groups (p = 0.541, log-rank). Furthermore, multivariate analysis that validated the effect of OS showed that high ORR and "high-ALC and PPL" were factors for a good prognosis (p < 0.001, HR = 0.321; p = 0.036, HR = 0.290).
The progression form of PNM had a worse prognosis than PPL in patients treated with eribulin. In breast cancer patients with eribulin chemotherapy, good systemic immune status, such as ALC ≥ 1500/μl, was associated with less progression, particularly metastasis, and better prognosis. Furthermore, the biomarker "high-ALC (ALC ≥ 1500/μl) and PPL" was particularly useful as a prognostic marker following eribulin chemotherapy.
在实体瘤反应评估标准（RECIST）诊断标准中，提出了预先存在疾病（PPL）进展和新转移（PNM）进展的概念，以区分治疗耐药性癌症的进展类型。根据癌症进展形式的肿瘤生物学，“PPL”形式表示侵袭，而“PNM”形式表示转移。另一方面，最近的研究侧重于炎症标志物作为全身肿瘤免疫反应的临床重要性。特别是，绝对淋巴细胞计数（ALC）是宿主免疫反应的指标。因此，我们开发了一种新的方法，将进展形式与 ALC 相结合。在这项研究中，我们在艾立布林化疗中对进展形式和 ALC 的联合评估进行了临床验证。
从 2011 年 8 月至 2019 年 4 月，共有 486 名局部晚期或转移性乳腺癌（MBC）患者接受了治疗。在这项研究中，仅纳入了 88 名接受艾立布林化疗的患者。根据 RECIST 标准 1.1 评估抗肿瘤疗效。为了测量 ALC，使用艾立布林治疗前采集的外周血样。本研究中 ALC 的截断值为 1500/μl，基于先前的研究。
PPL 组（71 例，80.7%）无进展生存期（PFS）（p = 0.022，对数秩）和总生存期（OS）（p < 0.001，对数秩）明显长于 PNM 组（17 例，19.3%）。在 ALC < 1500/μl 的 51 例患者中，PPL 组的预后明显优于 PNM 组（PFS：p = 0.035，OS：p < 0.001，对数秩）。另一方面，在 ALC≥1500/μl 的 37 例患者中，PPL 组的 OS 明显优于 PNM 组（p = 0.055，对数秩），但两组的 PFS 无显著差异（p = 0.541，对数秩）。此外，验证 OS 效果的多变量分析表明，高 ORR 和“高 ALC 和 PPL”是良好预后的因素（p < 0.001，HR = 0.321；p = 0.036，HR = 0.290）。
与接受艾立布林治疗的患者相比，PNM 进展形式的预后比 PPL 差。在接受艾立布林化疗的乳腺癌患者中，良好的全身免疫状态，如 ALC≥1500/μl，与进展，特别是转移减少和预后改善相关。此外，生物标志物“高 ALC（ALC≥1500/μl）和 PPL”作为艾立布林化疗后的预后标志物特别有用。
