Survival After Trimodality Therapy in Patients With Locally Advanced Esophagogastric Adenocarcinoma: Does Only a Complete Pathologic Response Matter?
Survival After Trimodality Therapy in Patients With Locally Advanced Esophagogastric Adenocarcinoma: Does Only a Complete Pathologic Response Matter?
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DOI：
10.1097/sla.0000000000004638
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发表时间：
2022-12-01
影响因子：
9
通讯作者：
Molena D
中科院分区：
文献类型：
--
作者：
Sihag S;Nobel T;Hsu M;De La Torre S;Tan KS;Janjigian YY;Ku GY;Tang LH;Wu AJ;Maron SB;Bains MS;Jones DR;Molena D
评估病理完全缓解（pCR）是否完全定义了治疗的主要病理反应和生存率的提高。食管胃腺癌三段式治疗后的pCR不常见，但与预后改善有关。然而，大多数临床试验和相关研究将pCR指定为主要终点。我们分析了1995年至2017年间接受三模式治疗的局部晚期食管腺癌患者的前瞻性数据库。采用Kaplan-Meier图，通过原发肿瘤床的治疗反应百分比（TR）和病理淋巴结分期（ypN0）来检测总生存期（OS）。用限制性三次样条函数的描述图研究了根据OS区分患者的TR的最佳阈值；使用Cox多变量分析对相关性进行量化。在788例患者中，中位随访时间为37.5个月（范围0.4-210.6）；中位OS为48.3个月（95% CI, 42.2-58.8）。无残余淋巴结疾病与生存率的提高独立相关（P<0.001）。90% - 99% TR和100% TR的生存曲线相似，90% TR时观察到OS改善概率的变化。在多变量分析中，与50% - 89%和<50% TR相比，90% - 99%和100% TR与OS改善独立相关。除了原发肿瘤床≥90% TR外，ypN0状态是三段式治疗主要病理反应的最强指标。这些发现可能允许将主要病理反应的定义从pCR扩展到≥90% TR和ypN0。这对今后的临床试验和相关研究具有重要意义。尽管病理完全缓解（pCR）与改善的长期生存相关，但它仅发生在20%-30%的食管胃腺癌（EAC）患者中。我们试图确定术前放化疗的主要病理反应是否超出pCR预测EAC患者的生存。治疗反应≥90%且无残留淋巴结累及与pCR相似的生存结果相关；这个阈值定义了主要的病理反应，代表了临床试验更有用的基准。
To evaluate whether pathologic complete response (pCR) exclusively defines major pathologic response to treatment with improved survival. pCR following trimodality therapy for esophagogastric adenocarcinoma is infrequent but associated with improved prognosis. Yet most clinical trials and correlative studies designate pCR as the primary endpoint. We analyzed our prospectively maintained database for patients who underwent trimodality therapy for locally advanced esophageal adenocarcinoma between 1995 and 2017. Overall survival (OS) was examined by percentage treatment response (TR) in the primary tumor bed and pathologic nodal stage (ypN0) using Kaplan-Meier plots. Optimal thresholds of TR for differentiating patients in terms of OS were investigated with descriptive plots using restricted cubic spline functions; associations were quantified using Cox multivariable analysis. Among 788 patients, median follow-up was 37.5 months (range, 0.4–210.6); median OS was 48.3 months (95% CI, 42.2–58.8). Absence of residual nodal disease was independently associated with improved survival (P<0.001). Survival curves for 90%–99% TR and 100% TR were similar, and a change in probability of improved OS was observed at 90% TR. On multivariable analysis, combining 90%–99% and 100% TR was independently associated with improved OS, compared with 50%–89% and <50% TR. ypN0 status is the strongest indicator of major pathologic response to trimodality therapy, in addition to ≥90% TR in the primary tumor bed. These findings may allow the definition of major pathologic response to be expanded, from pCR to ≥90% TR and ypN0. This has meaningful implications for future clinical trials and correlative studies. Although pathologic complete response (pCR) is associated with improved long-term survival, it occurs in only 20%–30% of patients with esophagogastric adenocarcinoma (EAC). We sought to determine whether a major pathologic response to preoperative chemoradiotherapy extends beyond pCR to predict survival in patients with EAC. Treatment response ≥90% with absence of residual lymph node involvement was associated with similar survival outcomes to pCR; this threshold defines a major pathologic response and represents a more useful benchmark for clinical trials.