Sarcomas are rare, heterogeneous mesenchymal neoplasms with various subtypes, each exhibiting unique genetic characteristics. Although studies have been conducted to improve the treatment for sarcomas, the specific development from normal somatic cells to sarcoma cells is still unclear and needs further research. The diagnosis of sarcomas depends heavily on the pathological examination, which is yet a difficult work and requires expert analysis. Advanced treatment like precise medicine optimizes the efficacy of treatment and the prognosis of sarcoma patients, yet, in sarcomas, more studies should be done to put such methods in clinical practice. The revolution of advanced technology has pushed the multi-omics approach to the front, and more could be learnt in sarcomas with such methods. Multi-omics combines the character of each omics techniques, analyzes the mechanism of tumor cells from different levels, which makes up for the shortage of single-omics, and gives us an integrated picture of bioactivities inside tumor cells. Multi-omics research of sarcomas has reached appreciable progress in recent years, leading to a better understanding of the mutation, proliferation, and metastasis of sarcomas. With the help of multi-omics approach, novel biomarkers were found, with promising effects in improving the process of diagnosis, prognosis anticipation, and treatment decision. By analyzing large amounts of biological features, subtype clustering could be done in a better precision, which may be useful in the clinical procedure. In this review, we summarized recent discoveries using multi-omics approach in sarcomas, discussed their merits and challenges, and concluded with future perspectives of the sarcoma research.

Opinion statementMelanoma is caused by a variety of somatic mutations, and among these mutations, BRAF mutation occurs most frequently and has routinely been evaluated as a critical diagnostic biomarker in clinical practice. The introduction of targeted agents for BRAF-mutant melanoma has significantly improved overall survival in a large proportion of patients. However, there is BRAF inhibitor resistance in most patients, and its mechanisms are complicated and need further clarification. Additionally, treatment approaches to overcome resistance have evolved rapidly, shifting from monotherapy to multimodality treatment, which has dramatically improved patient outcomes in clinical trials and practice. This review highlights the mechanisms of BRAF inhibitor resistance in melanoma and discusses the current state of its therapeutic approaches that can be further explored in clinical practice.

Background BRAF V600 mutation is the most common oncogenic alternation in melanoma and is visible in around 50% of cutaneous and 10%–15% of acral or mucosal subtypes. Currently, immunotherapy with anti‐PD‐1 blockade and dual‐targeted therapy with Dabrafenib plus trametinib (D + T) target therapy have been approved as adjuvant therapies for Stage III melanoma with BRAF V600 mutation. According to their phase III clinical trials, 3‐year recurrence‐free survival (RFS) is around 60% for both types of treatment. However, early disease control was slightly more effective with targeted therapy than immunotherapy. With different drug approval deadlines in China, anti‐PD1 monotherapy, D + T combination, and Vemurafenib (V) monotherapy have all been used in real clinical practice as adjuvant settings for stage III BRAF‐mut melanoma in recent years. We conducted this retrospective study to evaluate the efficacy of different treatments in the Chinese melanoma population. Methods Patients who underwent radical surgery and were diagnosed as Stage III melanoma harboring BRAF V600 mutation by pathological report were retrospectively identified at Fudan University Shanghai Cancer Center from January 2017 to December 2021. Patients with mucosal melanoma, or with follow‐up of <6 months, or receiving other adjuvant treatment were excluded. Pearson's chi‐squared test or Fisher's exact test was performed for univariable analysis of the different adjuvant groups. Log‐rank analysis was used to identify prognostic factors for relapse‐free survival (RFS). Results Ninety‐three patients with resected stage III melanoma with BRAF V600E mutation were identified in our study, including 25 patients receiving adjuvant anti‐PD‐1 immunotherapy (PD‐1), 25 receiving adjuvant D + T, 23 receiving V, and 20 patients with observation‐only (OBS). There were no statistical differences between treatment groups in baseline characteristics including age, gender, subtypes, primary thickness, ulceration, and nodal involvement. Median relapse‐free survival (RFS) time was not reached in the D + T group, 15 months in the V group, 15 months in the PD‐1 group, and 10 months in the OBS group, respectively. Compared to OBS, all three other groups showed a tendency to benefit from RFS, while only D + T achieved a statistical difference (p = 0.002). However, compared to D + T, anti‐PD‐1 monotherapy also showed significantly worse relapse control (p = 0.032). Conclusions For Chinese stage III melanoma with BRAF mutation, both novel targeted therapy and immunotherapy showed potential benefits in relapse‐free survival compared to observation only. Dual‐targeted D + T therapy may still be the best choice for adjuvant therapy because anti‐PD‐1 monotherapy has failed to report equivalent efficacy in real‐world practice.

Background Sentinel node biopsy (SNB) has become a critical part of standard surgical treatment for melanoma with no metastatic evidence. According to MSLT-II and DeCOG-SLT trials, for patients with positive sentinel nodes, immediate complete lymph node dissection (CLND) didn’t bring further benefit for patients’ survival. Argument remains among Chinese population with domination of acral subtypes whether CLND can be omitted. This study aims to investigate the impact of immediate CLND for SN positivity on relapse-free survival (RFS) in Chinese melanoma patients.Material and Methods Patients with acral or cutaneous melanoma of clinical stage I-II receiving SNB procedure and then detected with nodal micrometastasis were retrospectively identified at Fudan University Cancer Center (FUSCC) from January 2017 to December 2021. Clinicopathologic features and prognostic factors for RFS were analyzed.Results Among 381 patients who received SNB in the last five years, 130 (34%) cases with positive SN micrometastasis detected were identified in our study. 99 patients underwent immediate CLND while the other patients received observation alone. Among patients received CLND, the NSN positive rate was 22.2%. There were slightly less N1 stage in the CLND group compared to the non-CLND group, although the difference didn’t reach statistical significance (P = 0.075). There was no significant difference in RFS between the two groups (P = 0.184).Conclusions Immediate CLND didn’t bring further RFS benefit after an observation for Chinese melanoma with SN micrometastasis in real clinical practice, even for patients with acral subtype or more tumor burden such as thick Breslow invasion and ulceration.