高危软组织肉瘤的新辅助化疗：基于 Sarculator 的 ISG-STS 1001 随机试验风险分层分析。

Neoadjuvant chemotherapy in high-risk soft tissue sarcomas: A Sarculator-based risk stratification analysis of the ISG-STS 1001 randomized trial.

机构信息

Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Osteoncology, Bone and Soft Tissue Sarcomas, and Innovative Therapies Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.

出版信息

Cancer. 2022 Jan 1;128(1):85-93. doi: 10.1002/cncr.33895. Epub 2021 Oct 13.

DOI:10.1002/cncr.33895

PMID:34643947

Abstract

BACKGROUND

The value of neoadjuvant chemotherapy in soft tissue sarcoma (STS) is not completely understood. This study investigated the benefit of neoadjuvant chemotherapy according to prognostic stratification based on the Sarculator nomogram for STS.

METHODS

This study analyzed data from ISG-STS 1001, a randomized study that tested 3 cycles of neoadjuvant anthracycline plus ifosfamide (AI) or histology-tailored (HT) chemotherapy in adult patients with STS. The 10-year predicted overall survival (pr-OS) was estimated with the Sarculator and was stratified into higher (10-year pr-OS < 60%) and lower risk subgroups (10-year pr-OS ≥ 60%).

RESULTS

The median pr-OS was 0.63 (interquartile range [IQR], 0.51-0.72) for the entire study population, 0.62 (IQR, 0.51-0.70) for the AI arm, and 0.64 (IQR, 0.51-0.73) for the HT arm. Three- and 5-year overall survival (OS) were 0.86 (95% confidence interval [CI], 0.82-0.93) and 0.81 (95% CI, 0.71-0.86) in lower risk patients and 0.69 (95% CI, 0.70-0.85) and 0.59 (95% CI, 0.51-0.72) in the higher risk patients (log-rank test, P = .004). In higher risk patients, the 3- and 5-year Sarculator-predicted and study-observed OS rates were 0.68 and 0.58, respectively, and 0.85 and 0.66, respectively, in the AI arm (P = .04); the corresponding figures in the HT arm were 0.69 and 0.60, respectively, and 0.69 and 0.55, respectively (P > .99). In lower risk patients, the 3- and 5-year Sarculator-predicted and study-observed OS rates were 0.85 and 0.80, respectively, and 0.89 and 0.82, respectively, in the AI arm (P = .507); the corresponding figures in the HT arm were 0.87 and 0.81, respectively, and 0.86 and 0.74, respectively (P = .105).

CONCLUSIONS

High-risk patients treated with AI performed better than predicted, and this adds to the evidence for the efficacy of neoadjuvant AI in STS.

LAY SUMMARY

People affected by soft tissue sarcomas of the extremities and trunk wall are at some risk of developing metastasis after surgery. Preoperative or postoperative chemotherapy has been tested in clinical trials to reduce the chances of distant metastasis. However, study findings have not been conclusive. This study stratified the risk of metastasis for people affected by sarcomas who were included in a clinical trial testing neoadjuvant chemotherapy. Exploiting the prognostic nomogram Sarculator, it found a benefit for chemotherapy when the predicted risk, based on patient and tumor characteristics, was high.

摘要

背景

新辅助化疗在软组织肉瘤（STS）中的价值尚未完全了解。本研究根据 Sarculator 列线图对 STS 患者进行的预后分层，研究了新辅助化疗的获益。

方法

本研究分析了 ISG-STS 1001 的数据，这是一项随机研究，在 STS 成人患者中测试了 3 个周期的新辅助蒽环类药物加异环磷酰胺（AI）或基于组织学的（HT）化疗。使用 Sarculator 估计了 10 年的预测总生存（pr-OS），并根据 10 年 pr-OS 将患者分为高风险（10 年 pr-OS < 60%）和低风险亚组（10 年 pr-OS ≥ 60%）。

结果

整个研究人群的中位 pr-OS 为 0.63（四分位距 [IQR]，0.51-0.72），AI 组为 0.62（IQR，0.51-0.70），HT 组为 0.64（IQR，0.51-0.73）。低风险患者的 3 年和 5 年总生存率（OS）分别为 0.86（95%置信区间 [CI]，0.82-0.93）和 0.81（95% CI，0.71-0.86），高风险患者分别为 0.69（95% CI，0.70-0.85）和 0.59（95% CI，0.51-0.72）（对数秩检验，P =.004）。在高风险患者中，Sarculator 预测和研究观察的 3 年和 5 年 OS 率分别为 0.68 和 0.58，分别为 0.85 和 0.66，分别为 AI 组（P =.04）；HT 组的相应数据分别为 0.69 和 0.60，分别为 0.69 和 0.55（P >.99）。在低风险患者中，Sarculator 预测和研究观察的 3 年和 5 年 OS 率分别为 0.85 和 0.80，分别为 0.89 和 0.82，分别为 AI 组（P =.507）；HT 组的相应数据分别为 0.87 和 0.81，分别为 0.86 和 0.74（P =.105）。