Bode-Lesniewska Beata, Dürr Hans Roland, Wang Dian, Naghavi Arash, Montreuil Julien, Fischer Tim, Ghert Michelle, Lazarides Alexander, Lindner Lars, Martin-Broto Javier, Mazza Malena, Scanferla Roberto, Studer Gabriela, Temple H Tom, Wunder Jay, Fuchs Bruno
Institute for Pathology, LUKS University Hospital, Spitalstrasse 1, 6000 Luzern, Switzerland.
Schwerpunkt Tumororthopädie, Orthopädische Klinik der LMU München, Marchionistrasse 15, 81377 Munich, Germany.
Cancers (Basel). 2025 May 26;17(11):1779. doi: 10.3390/cancers17111779.
Soft-tissue sarcomas (STSs) represent a heterogeneous group of malignancies with widely varying treatment responses and biological behaviors. While spontaneous necrosis (present at diagnosis) is recognized in established sarcoma grading systems, the prognostic significance of therapy-induced necrosis remains uncertain. Inconsistent definitions, methodological variability, and clinical confounders further complicate the interpretation of necrosis as an independent prognostic marker. This communication synthesizes findings from an international, multidisciplinary webinar hosted by the Sarcoma Academy, critically assessing the utility of therapy-induced necrosis in STS management. Discussions encompassed surgical, pathological, oncological, and radiological perspectives, emphasizing how necrosis is defined, measured, and contextualized in patient care. Heterogeneity in STS subtypes, varied treatment protocols, and sampling inconsistencies challenge the prognostic value of post-treatment necrosis. While substantial necrosis may sometimes signal effective therapy, it can also reflect the tumor's aggressive nature. The panel underscored the utility of measuring the percentage of viable tumor cells, rather than necrosis alone, to obtain a more standardized and reproducible measure of therapy response. Emerging approaches-such as radiomics, molecular profiling, immune-based analyses, and real-world evidence (RWE) protocols-offer promising avenues for refining prognostication and guiding personalized therapy in STS. A focus solely on therapy-induced necrosis is insufficient to predict outcomes in STS. Instead, a multidisciplinary framework-combining standardized pathology protocols, quantification of viable tumor cells, advanced imaging, and innovative clinical trial designs-can better capture both treatment effects and underlying tumor biology. Future collaborative studies and hybrid trial methodologies are needed to determine which STS subgroups gain the most from intensified treatments aimed at maximizing necrosis, and how to balance such interventions with surgical considerations, toxicity, and overall patient well-being.
软组织肉瘤（STSs）是一组异质性恶性肿瘤，其治疗反应和生物学行为差异很大。虽然在既定的肉瘤分级系统中已认识到自发坏死（诊断时存在），但治疗诱导坏死的预后意义仍不确定。定义不一致、方法学差异和临床混杂因素进一步使将坏死作为独立预后标志物的解释复杂化。本通讯综合了肉瘤学会主办的一次国际多学科网络研讨会的结果，批判性地评估了治疗诱导坏死在STS管理中的效用。讨论涵盖了外科、病理、肿瘤学和放射学观点，强调了在患者护理中如何定义、测量坏死并将其置于具体情境中。STS亚型的异质性、不同的治疗方案和取样不一致对治疗后坏死的预后价值提出了挑战。虽然大量坏死有时可能表明治疗有效，但它也可能反映肿瘤的侵袭性。专家小组强调，测量存活肿瘤细胞的百分比，而不是仅测量坏死，以获得更标准化和可重复的治疗反应测量方法的效用。新兴方法，如放射组学、分子谱分析、基于免疫的分析和真实世界证据（RWE）方案，为完善STS的预后评估和指导个性化治疗提供了有希望的途径。仅关注治疗诱导坏死不足以预测STS的结果。相反，一个多学科框架，结合标准化病理方案、存活肿瘤细胞定量、先进成像和创新临床试验设计，可以更好地捕捉治疗效果和潜在肿瘤生物学。未来需要开展合作研究和采用混合试验方法，以确定哪些STS亚组能从旨在最大化坏死的强化治疗中获益最多，以及如何在手术考虑、毒性和患者总体福祉之间平衡此类干预措施。
