Huang Lin, Qin Changlong, Pu Dan, Liu Yanyang, Bassi Massimiliano, Käsmann Lukas, Li Lu
Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Thoracic Surgery Unit, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
Transl Lung Cancer Res. 2022 Aug;11(8):1713-1721. doi: 10.21037/tlcr-22-572.
Despite significant recent advances in characterizing the molecular pathogenesis of undifferentiated small round cell sarcoma (USRCS), rare cases without reported gene alterations remain unclassified. To date, the efficacy and prognostic biomarker of immunotherapy in the treatment of unresectable USRCS has not been demonstrated, especially when these cases occurring in uncommon thoracic visceral organs with a novel gene fusion.
We report a case of locally advanced and unresectable USRCS of the lung (cT4N1M0) with SDCCAG8-AKT3 fusion identified by RNA-based next-generation sequencing (NGS). He initially admitted to our hospital chiefly complained of cough and dyspnea without any intervention. Imaging examinations, positron emission tomography/computed tomography (PET/CT), tumor biopsy, and a series of molecular tests based on tumor specimens were conducted for diagnosis. The molecular tests supplied more information delineating the case's molecular characteristics including mutation, CD274 amplification, high tumor mutational burden (TMB-H), and high microsatellite instability (MSI-H). Multiple immunofluorescence (mIF) staining further revealed a specific immune-microenvironment phenotype with a 100% programmed death ligand 1 (PD-L1) expression and type II tumor immunity in the microenvironment (type II TIME) of this case. This 31-year-old non-smoking male received vincristine sulfate, dactinomycin, and cyclophosphamide (VAC) regimen chemotherapy combined with pembrolizumab and sequential radiotherapy. He had maintained a partial response (PR) according to response evaluation criteria in solid tumors (RECIST) 1.1 and a good quality of life for almost 14 months except for mild loss of appetite and hair loss after chemotherapy to the latest follow-up date.
Our study showed a rare case of lung USRCS harboring a novel SDCCAG8-AKT3 fusion. And we indicated that a comprehensive treatment including the combination of systemic VAC chemotherapy and anti-programmed cell death protein 1 (PD-1) immunotherapy, and sequential radiotherapy could be considered for similar cases, prophylactic managements of chemotherapy-related myelosuppression and urotoxicity should be administrated along with chemotherapy as well. Tumor immune microenvironment analysis and gene sequencing are recommended to obtain more prognostic biomarkers in addition to routine pathologic examinations in diagnosis and treatment of USRCS.
尽管最近在未分化小圆细胞肉瘤（USRCS）分子发病机制的研究方面取得了重大进展，但仍有罕见病例未报告基因改变，无法分类。迄今为止，免疫疗法在不可切除的USRCS治疗中的疗效和预后生物标志物尚未得到证实，尤其是当这些病例发生在具有新型基因融合的罕见胸内脏器时。
我们报告了一例经基于RNA的二代测序（NGS）鉴定为SDCCAG8-AKT3融合的局部晚期且不可切除的肺USRCS（cT4N1M0）病例。他最初因咳嗽和呼吸困难入院，未接受任何干预。进行了影像学检查、正电子发射断层扫描/计算机断层扫描（PET/CT）、肿瘤活检以及一系列基于肿瘤标本的分子检测以明确诊断。分子检测提供了更多关于该病例分子特征的信息，包括突变、CD274扩增、高肿瘤突变负荷（TMB-H）和高微卫星不稳定性（MSI-H）。多重免疫荧光（mIF）染色进一步揭示了一种特定的免疫微环境表型，该病例的微环境中程序性死亡配体1（PD-L1）表达率为100%，且为II型肿瘤免疫（II型肿瘤免疫微环境）。这位31岁的不吸烟男性接受了硫酸长春新碱、放线菌素D和环磷酰胺（VAC）方案化疗联合帕博利珠单抗及序贯放疗。截至最新随访日期，根据实体瘤疗效评价标准（RECIST）1.1，他维持了部分缓解（PR），生活质量良好，化疗后除了有轻微食欲减退和脱发外，已持续近14个月。
我们的研究展示了一例罕见的携带新型SDCCAG8-AKT3融合的肺USRCS病例。我们指出，对于类似病例可考虑采用包括全身VAC化疗联合抗程序性细胞死亡蛋白1（PD-1）免疫疗法及序贯放疗的综合治疗方案，同时化疗时应采取预防化疗相关骨髓抑制和尿路毒性的管理措施。除了在USRCS的诊断和治疗中进行常规病理检查外，建议进行肿瘤免疫微环境分析和基因测序以获得更多预后生物标志物。
