YTHDF1 promotes the osteolytic bone metastasis of breast cancer via inducing EZH2 and CDH11 translation.

Bone metastasis is common in breast cancer and more effective therapies are required, however, its molecular mechanism is poorly understood. Additionally, the role of the m6A reader YTHDF1 in bone metastasis of breast cancer has not been reported. Here, we reveal that the increased expression of YTHDF1 is clinically correlated with breast cancer bone metastases. YTHDF1 promotes migration, invasion, and osteoblast adhesion and induces osteoclast differentiation of cancer cells in vitro and vivo. Mechanically, RNA-seq, MeRIP-seq and RIP-seq analysis, and molecular biology experiments demonstrate that YTHDF1 translationally enhances EZH2 and CDH11 expression by reading m6A-enriched sites of their transcripts. Moreover, adeno-associated virus (AAV) was used to deliver shYTHDF1 (shYTHDF1-AAV) in intratibial injection models, eliciting a significant suppressive effect on breast cancer bone metastatic formation and osteolytic destruction. Overall, we uncovered that YTHDF1 promotes osteolytic bone metastases of breast cancer by inducing EZH2 and CDH11 translation.

Osteosarcoma-targeted Cu and Ce based oxide nanoplatform for NIR II fluorescence/magnetic resonance dual-mode imaging and ros cascade amplification along with immunotherapy.

BACKGROUND: As the lethal bone tumor, osteosarcoma often frequently occurs in children and adolescents with locally destructive and high metastasis. Distinctive kinds of nanoplatform with high therapeutical effect and precise diagnosis for osteosarcoma are urgently required. Multimodal optical imaging and programmed treatment, including synergistic photothermal-chemodynamic therapy (PTT-CDT) elicits immunogenetic cell death (ICD) is a promising strategy that possesses high bio-imaging sensitivity for accurate osteosarcoma delineating as well as appreciable therapeutic efficacy with ignorable side-effects. METHODS AND RESULTS: In this study, mesoporous Cu and Ce based oxide nanoplatform with Arg-Gly-Asp (RGD) anchoring is designed and successfully constructed. After loading with indocyanine green, this nanoplatform can be utilized for precisely targeting and efficaciously ablating against osteosarcoma via PTT boosted CDT and the closely following ICD stimulation both in vitro and in vivo. Besides, it provides off-peak fluorescence bio-imaging in the second window of near-infrared region (NIR II, 1000-1700 nm) and Magnetic resonance signal, serves as the dual-mode contrast agents for osteosarcoma tissue discrimination. CONCLUSION: Tumor targeted Cu&Ce based mesoporous nanoplatform permits efficient osteosarcoma suppression and dual-mode bio-imaging that opens new possibility for effectively diagnosing and inhibiting the clinical malignant osteosarcoma.

Hypoxic Exosomal circPLEKHM1-Mediated Crosstalk between Tumor Cells and Macrophages Drives Lung Cancer Metastasis.

Intercellular communication often relies on exosomes as messengers and is critical for cancer metastasis in hypoxic tumor microenvironment. Some circular RNAs (circRNAs) are enriched in cancer cell-derived exosomes, but little is known about their ability to regulate intercellular communication and cancer metastasis. Here, by systematically analyzing exosomes secreted by non-small cell lung cancer (NSCLC) cells, a hypoxia-induced exosomal circPLEKHM1 is identified that drives NSCLC metastasis through polarizing macrophages toward to M2 type. Mechanistically, exosomal circPLEKHM1 promoted PABPC1-eIF4G interaction to facilitate the translation of the oncostatin M receptor (OSMR), thereby promoting macrophage polarization for cancer metastasis. Importantly, circPLEKHM1-targeted therapy significantly reduces NSCLC metastasis in vivo. circPLEKHM1 serves as a prognostic biomarker for metastasis and poor survival in NSCLC patients. This study unveils a new circRNA-mediated mechanism underlying how cancer cells crosstalk with macrophages within the hypoxic tumor microenvironment to promote metastasis, highlighting the importance of exosomal circPLEKHM1 as a prognostic biomarker and therapeutic target for lung cancer metastasis.

Wide resection and extensive reconstruction of soft tissue sarcomas in the upper limb. A case report.

INTRODUCTION: Upper limb soft tissue sarcomas are extremely rare and can be misdiagnosed as benign, leading to unplanned excisions. Unplanned excisions and local recurrences pose significant challenges for the subsequent treatment of patients. PRESENTATION OF CASE: A patient with a forearm soft tissue sarcoma who underwent unplanned excisions and experienced multiple recurrences. In the most recent treatment, she underwent wide tumor excision combined with thigh free flap transplantation for reconstruction. The reconstruction surgery successfully addressed the extensive soft tissue defect. During the three-year follow-up, there was no tumor recurrence observed, alongside the restoration of upper arm function. DISCUSSION: Challenges and considerations in the treatment of soft tissue sarcomas (STS) are discussed. CONCLUSION: Unplanned excisions and local recurrences of upper limb soft tissue sarcomas present significant challenges for surgery. Patients should be referred to specialized cancer centers for multidisciplinary diagnosis and treatment.

Soft-tissue reconstruction with pedicled vertical rectus abdominis myocutaneous flap after total or high sacrectomy for giant sacral tumor.

BACKGROUND: The large soft-tissue defect after total or high sacrectomy for giant sacral tumor induces high incidence of wound complications. It remains a huge challenge to reconstruct the soft-tissue defect and achieve the preferred clinical outcome. METHODS: A total of 27 patients undergoing one-stage total or high sacrectomy for giant sacral tumors between 2016 and 2021 in a tertiary university hospital were retrospectively reviewed. Participants were divided into two groups. Thirteen patients underwent a pedicled vertical rectus abdominis myocutaneous (VRAM) flap reconstruction, whereas 14 patients underwent a conventional wound closure. Patient's clinical characteristics, surgical duration, postoperative complications, and outcomes were compared between the two groups. RESULTS: Patients in VRAM and non-VRAM groups were similar in baseline characteristics. The mean tumor size was 12.85 cm (range: 10-17 cm) in VRAM group and 11.79 cm (range: 10-14.5 cm) in non-VRAM group (P = 0.139). The most common giant sacral tumor is chordoma. Patients in VRAM group had a shorter length of drainage (9.85 vs 17.14 days), postoperative time in bed (5.54 vs 17.14 days), and total length of stay (19.46 vs 33.36 days) compared with patients in non-VRAM group. Patients in the VRAM group had less wound infection and debridement than patients in non-VRAM group (15.4% vs 57.1%, P < 0.001). CONCLUSIONS: This study demonstrates the advantages of pedicled VRAM flap reconstruction of large soft-tissue defects after high or total sacrectomy using the anterior-posterior approach. This choice of reconstruction is better than direct wound closure in terms of wound infection, length of drainage, and total length of stay.

PARVB promotes malignant melanoma progression and is enhanced by hypoxic conditions.

Beta-Parvin (PARVB) is an actin-binding protein with functionality in extracellular matrix binding. Recent studies suggest its potential as a biomarker for various cancers, given its role in governing several malignancies. Yet, its involvement and modulatory mechanisms in malignant melanoma remain under-explored.  In this research, we undertook a comprehensive pan-cancer analysis centered on PARVB. We probed its aberrant expression and prognostic implications, and assessed correlations between PARVB expression and immunocyte infiltration. This expression was subsequently corroborated using clinical samples. Both in vitro and in vivo, we discerned the functional ramifications of PARVB on melanoma. Furthermore, we scrutinized how HIF-1α/2α modulates PARVB and initiated a preliminary investigation into potential downstream pathways influenced by PARVB. Our results illuminate that elevated PARVB expression manifests across various tumors and significantly influences the prognosis of multiple cancers, emphasizing its peculiar expression and prognostic relevance in melanoma. Augmented PARVB levels were inversely proportional to immunocyte penetration in melanoma. Silencing PARVB curtailed cellular proliferation, migration, and invasion in vitro and decelerated tumor expansion in vivo. Notably, hypoxic conditions, triggering HIF-1α/2α activation, appear to elevate PARVB expression by anchoring to the hypoxia-specific responsive element within the PARVB promoter. Enhanced PARVB levels seem intertwined with the activation of cellular proliferation circuits and the damping of inflammatory trajectories. Collectively, these revelations posit PARVB as a potential prognostic indicator and therapeutic linchpin for malignant melanoma.

Essential genes analysis reveals small ribosomal subunit protein eS28 may be a prognostic factor and potential vulnerability in osteosarcoma.

Background: Osteosarcoma, the most common primary malignant bone tumor, is currently treated with surgery combined with chemotherapy, but the limited availability of targeted drugs contributes to a poor prognosis. Identifying effective therapeutic targets is crucial for improving the prognosis of osteosarcoma patients. Methods: We screened the DepMap database to identify essential genes as potential therapeutic targets for osteosarcoma. Gene Set Enrichment Analysis (GSEA) was employed to elucidate the biological roles of these essential genes. Promising candidates were filtered through univariate and multivariate Cox analyses, as well as Kaplan-Meier survival analyses using the GSE21257-OSA and TARGET-OSA datasets. The functional role of the target gene was assessed through cell experiments. Additionally, an in situ nude mice model was established to observe the gene's function, and RNA sequencing was utilized to explore the underlying molecular mechanism. Results: A total of 934 essential genes were identified based on their effects (Chronos) using the DepMap database. These genes were primarily enriched in the ribosome pathway according to GSEA analysis. Among them, 195 genes were associated with the ribosome pathway. Rps28, Rps7, and Rps25 were validated as promising candidates following univariate and multivariate Cox analyses of the TARGET-OSA and GSE21257-OSA datasets. Kaplan-Meier survival analyses indicated Rps28 represented an especially promising target, with high expression correlating with poor prognosis. Knockdown of small ribosomal subunit protein eS28, the protein of Rps28, inhibited proliferation, migration, and invasion in both in vitro and in vivo experiments. Silencing RPS28 affected the MAPK signaling pathway in osteosarcoma. Conclusion: In summary, Rps28 has been identified as an essential gene for osteosarcoma cell survival and eS28 may serve as a potential vulnerability in osteosarcoma.

Single-cell profiling of the microenvironment in human bone metastatic renal cell carcinoma.

Bone metastasis is of common occurrence in renal cell carcinoma with poor prognosis, but no optimal treatment approach has been established for bone metastatic renal cell carcinoma. To explore the potential therapeutic targets for bone metastatic renal cell carcinoma, we profile single cell transcriptomes of 6 primary renal cell carcinoma and 9 bone metastatic renal cell carcinoma. We also include scRNA-seq data of early-stage renal cell carcinoma, late-stage renal cell carcinoma, normal kidneys and healthy bone marrow samples in the study to better understand the bone metastasis niche. The molecular properties and dynamic changes of major cell lineages in bone metastatic environment of renal cell carcinoma are characterized. Bone metastatic renal cell carcinoma is associated with multifaceted immune deficiency together with cancer-associated fibroblasts, specifically appearance of macrophages exhibiting malignant and pro-angiogenic features. We also reveal the dominance of immune inhibitory T cells in the bone metastatic renal cell carcinoma which can be partially restored by the treatment. Trajectory analysis showes that myeloid-derived suppressor cells are progenitors of macrophages in the bone metastatic renal cell carcinoma while monocytes are their progenitors in primary tumors and healthy bone marrows. Additionally, the infiltration of immune inhibitory CD47+ T cells is observed in bone metastatic tumors, which may be a result of reduced phagocytosis by SIRPA-expressing macrophages in the bone microenvironment. Together, our results provide a systematic view of various cell types in bone metastatic renal cell carcinoma and suggest avenues for therapeutic solutions.

[Retracted] MicroRNA-493 inhibits the proliferation and invasion of osteosarcoma cells through directly targeting specificity protein 1.

[This retracts the article DOI: 10.3892/ol.2018.8268.].

Surgical resection of soft tissue metastasis in cancers: A single-center study of 77 cases over a 7-year period.

INTRODUCTION: Soft tissue metastasis (STM) of cancers, encompassing skeletal muscle and subcutaneous tissue metastasis, is less common due to unique homeostatic conditions. With longer life expectancy and the advent of new imaging modalities, clinical physicians will increasingly encounter and manage such cases. This study retrospectively reviewed cases of STM in visceral cancers who underwent surgery at Fudan University Shanghai Cancer Center over a 7-year period. METHODS: Data were collected through a comprehensive review of medical records, including demographic variables, primary tumor characteristics, surgical data, tumor pathology, and outcomes. Survival analysis was performed using Kaplan-Meier curves. RESULTS: The study included 77 cases with a median follow-up period of 854 days. The most common primary tumor sites were the lung (11) and breast (10). The abdominal wall was the most frequent site of metastasis. The combination of visceral metastasis, age over 52 years, and a history of primary tumor correlates with a poorer prognosis. Surgical-related metastases are associated with a higher degree of differentiation. Additionally, we have identified a better prognosis for patients with cancer of unknown primary (CUP) exhibiting potential resectable soft tissue metastases. CONCLUSION: The combination of visceral metastasis, age over 52 years, and a history of primary tumor suggest a poorer prognosis. While no significant impact on survival was observed for patients with lymph node metastasis. Surgical-related metastases are associated with a higher degree of differentiation. CUP patients with potentially resectable soft tissue metastases should be considered for surgical intervention.

Establishment of a staging system for visceral sarcoma.

BACKGROUND: Visceral sarcoma is a rare malignancy with a poor prognosis. However, there is no recommended prognostic staging system for the malignant disease. METHOD: We analyzed the data of patients diagnosed with primary soft tissue sarcoma (STS) of the abdomen and thoracic visceral organs between 2006 and 2017 at our hospital. Prognostic factors (size, tumor grade, and lymph node metastasis) were analyzed in our cohort (n = 203) and the SEER validation cohort (n = 5826). RESULTS: Tumor size, grade, and lymph node metastasis were important prognostic factors for visceral sarcoma in both our and the SEER cohorts. Based on these prognostic factors, we established a new staging system for visceral sarcoma, by which patients could be stratified into clinically meaningful and non-overlapping stages in both our cohort and the SEER validation series. Moreover, the area under the curve (AUC) value of the staging system for 5-year survival was 0.84 (95% CI: 0.78-0.89) in our series and 0.80 (95% CI: 0.79-0.81) in SEER series, respectively. In addition, compared with the widely used FIGO staging system for female genital sarcoma, the visceral sarcoma staging system could more effectively and reliably stratify patients into four different prognostic groups. CONCLUSIONS: The visceral sarcoma staging system is applicable for STS of the abdomen and thoracic visceral organs and is better than the current FIGO staging system for female genital sarcoma and should be incorporated into the AJCC Cancer Staging Manual.

IOX1 epigenetically enhanced photothermal therapy of 3D-printing silicene scaffolds against osteosarcoma with favorable bone regeneration.

Osteosarcoma (OS) is the third most common malignancy in adolescence. Currently, the treatments of OS confront great obstacles of tumor recurrence and critical bone defects after surgery, severely affecting the survival rates and living qualities of patients. Hence, it is urged to develop distinct biomaterials with both efficient tumor therapeutic and osteogenic functions. Although photothermal therapy (PTT) has aroused expanding interest, characterizing negligible invasiveness and high spatiotemporal adjustment, few studies discussed its drawbacks, such as thermal injury to adjacent normal tissue and exceeded laser power density, implying that focusing on sensitizing OS to PTT instead of simply elevating the laser power density may be a fresh way to enhance the PTT efficacy and attenuate the side/adverse effects. Herein, we successfully constructed 3D-printing silicene bioactive glass scaffolds with preferable PTT efficacy at the second near-infrared (NIR-II) biowindow and outstanding osteogenic biofunctions owing to the release of bioactive elements during degradation. Impressively, a histone demethylase inhibitor, IOX1, was introduced before PTT to sensitize OS to thermal therapy and minimize the side/adverse effects. This work offered a distinctive paradigm for optimizing the PTT efficacy of osteogenic scaffolds against OS with epigenetic modulation agents.

Prognostic value of the number of biopsied sentinel lymph nodes for Chinese patients with melanoma: A single-center retrospective study.

BACKGROUND: Sentinel lymph node biopsy (SLNB) helps to determine accurate pathological stages and facilitates strategies for regional disease control in melanoma. However, whether the number of biopsied sentinel lymph nodes (SLNs) influences the patients' survival is rarely investigated. METHODS: Acral or cutaneous melanoma patients with no history of nodal disease who received SLNB in Fudan University Shanghai Cancer Center (FUSCC) from January 1, 2017, to December 31, 2021 were retrospectively enrolled. Clinicopathological variables including Breslow index, ulceration, number of positive SLNs, SLN/non-SLN status were analyzed. The pathologic nodal (pN) stage and pathological stage were defined. RESULTS: A total of 381 eligible patients were enrolled in this study, of whom 132 (34.7%) patients were diagnosed with SLN-positive. The median number of biopsied SLNs was 2 (range: 1 to 20). Different numbers of biopsied SLNs did not influence the release-free survival (RFS) of the general patients. However, patients with >2 SLNs had a longer RFS than those with 1-2 SLNs in T4, N1a group and those who rejected complete lymph node dissection (CLND). CONCLUSIONS: In patients with T4 melanomas, N1a melanomas and those that did not undergo a CLND, the prognosis of those with three or more SLNs retrieved seemed to be improved.

Does primary tumor resection improve survival for patients with sarcomas of pelvic bones, sacrum, and coccyx who have metastasis at diagnosis ?

BACKGROUND: Recent studies demonstrated that primary tumor resection (PTR) improves survival of patients with metastatic bone sarcomas. However, it remains quite unclear regarding the role of PTR in the treatment of sarcomas of pelvic bones with synchronous metastasis at diagnosis. METHODS: Using the Surveillance, Epidemiology, and End Results Program, we enrolled a total of 385 patients with sarcomas of pelvic bones, sacrum, and coccyx who have metastasis at initial diagnosis, including 139 patients with osteosarcoma, 176 with Ewing sarcoma, and 70 with chondrosarcoma. Association between PTR and disease-specific survival (DSS) were investigated using the univariable and multivariable Cox regression models. Hazard ratio (HR) and 95% confidence interval (CI) were reported. Representative institutional PTR strategies and clinical outcomes for patients with metastatic pelvic sarcomas from our cancer center were displayed. RESULTS: The usage rate of PTR was 28.1% (39/139) in osteosarcoma, 13.6% (24/176) in Ewing sarcoma, and 41.4% (29/70) in chondrosarcoma with synchronous metastatic lesions. PTR was not associated with an improved DSS for metastatic pelvic osteosarcoma (HR = 0.686, 95% CI = 0.430 ~ 1.094, P = 0.113) and Ewing sarcoma (HR = 0.580, 95% CI = 0.291 ~ 1.154, P = 0.121). The use of PTR was associated with an improved DSS for metastatic pelvic chondrosarcoma (HR = 0.464, 95% CI = 0.225 ~ 0.954, P = 0.037). CONCLUSION: Primary lesion resection may provide a survival benefit for metastatic chondrosarcoma, but not for osteosarcoma and Ewing sarcoma of pelvic bones, sacrum, and coccyx. This population-based study recommends an active surgical intervention for metastatic chondrosarcoma while non-surgical treatment for metastatic osteosarcoma and Ewing sarcoma of the pelvis in terms of survival improvement.

Prediction of nonsentinel lymph node metastasis in acral melanoma with positive sentinel lymph nodes.

BACKGROUND: Metastasis in a nonsentinel lymph node (non-SLN) is an unfavorable independent prognostic factor in cutaneous melanoma (CM). Recent data did suggest potential value of completion lymph node dissection (CLND) in CM patients with non-SLN metastasis. Prediction of non-SLN metastasis assists clinicians in deciding on adjuvant therapy without CLND. We analyzed risk factors and developed a prediction model for non-SLN status in acral melanoma (AM). METHODS: This retrospective study enrolled 656 cases of melanoma who underwent sentinel lymph node biopsy at Fudan University Shanghai Cancer Center from 2009 to 2017. We identified 81 SLN + AM patients who underwent CLND. Clinicopathologic data, including SLN tumor burden and non-SLN status were examined with Cox and Logistics regression models. RESULTS: Ulceration, Clark level, number of deposits in the SLN (NumDep) and maximum size of deposits (MaxSize) are independent risk factors associated with non-SLN metastases. We developed a scoring system that combines ulceration, the cutoff values of Clark level V, MaxSize of 2 mm, and NumDep of 5 to predict non-SLN metastasis with an efficiency of 85.2% and 100% positive predictive value in the high-rank group (scores of 17-24). CONCLUSIONS: A scoring system that included ulceration, Clark level, MaxSize, and NumDep is reliable and effective for predicting non-SLN metastasis in SLN-positive AM.

Implant failure and revision strategies after total spondylectomy for spinal tumors.

Background: Although there have been several risk factors reported for implant failure (IF), little consensus exists. Potential applicable measures to protect patients from IF are relatively few. This study aimed to discover new risk factors for IF and explore potential protective measures from IF after total spondylectomy for spinal tumors. Methods: A total of 145 patients undergoing total spondylectomy for thoracic and lumbar spinal tumors between 2010 and 2021 were included from three tertiary university hospitals. Patient demographic and surgical characteristics and follow-up outcomes were collected. Results: During a mean follow-up of 53.77 months (range, 12 to 149 months), 22 of 145 patients (15.17%) developed IF. Patients undergoing thoracolumbar junctional region (T12/L1) resection were more likely to develop IF compared to those undergoing surgery at other vertebral levels (HR = 21.622, 95% CI = 3.567-131.084, P = 0.001). Patients undergoing titanium mesh cage reconstruction were more likely to develop IF compared to patients undergoing expandable titanium cage reconstruction (HR = 8.315, 95% CI = 1.482-46.645, P = 0.016). Patients with bone cement augmentation around the cage were less likely to develop IF compared to those not receiving bone cement augmentation (HR = 0.015, 95% CI = 0.002-0.107, P < 0.001). Of the 22 patients with IF, 14 (63.63%) accepted personalized revision surgery. Conclusion: The use of an expandable cage and the use of bone cement augmentation around the anterior column support cage are protective measures against IF after total spondylectomy.

Optimal timing of re-excision in synovial sarcoma patients: Immediate intervention versus waiting for local recurrence.

BACKGROUND: To investigate the difference in efficacy of re-excision in synovial sarcoma patients with and without residual tumor following unplanned excision, and to compare the prognostic outcomes of immediate re-excision versus waiting for local recurrence. METHOD: This study included synovial sarcoma patients who underwent re-excision at our center between 2009 and 2019, categorized into groups based on unplanned excision and local recurrence. Analyzed endpoints included overall survival (OS), local recurrence-free survival (LRFS), and distant relapse-free survival (DRFS). Prognostic factors associated with these three different survival outcomes were analyzed through the use of Kaplan-Meier curves and Cox regression approaches. RESULT: In total, this study incorporated 109 synovial sarcoma patients, including 32 (29.4%) with no residual tumor tissue identified after re-excision, 31 (28.4%) with residual tumor tissue after re-excision, and 46 (42.2%) with local recurrence after initial excision. Patients were assessed over a median 52-month follow-up period. The respective 5-year OS, 5-year LRFS, and 5-year DRFS rates were 82.4%, 76.7%, and 74.2% for the nonresidual group, 80.6%, 80.4%, and 77.3% for the residual tumor tissue group, and 63.5%, 50.7%, and 46.3% for the local recurrence group. There was no significant difference in OS of nonresidual group and residual group patients after re-excision (p = 0.471). Concurrent or sequential treatment with chemotherapy and radiotherapy significantly reduced the risk of metastasis and mortality when compared with noncombined chemoradiotherapy, and was more effective in the local recurrence group (p < 0.05). CONCLUSION: Prompt and adequate re-excision is crucial for patients with synovial sarcoma who undergo initial inadequate tumor excision, and their prognosis is significantly better compared with patients who delay re-excision until local recurrence.

A real-world study of adjuvant anti-PD -1 immunotherapy on stage III melanoma with BRAF, NRAS, and KIT mutations.

BACKGROUND: Melanoma frequently harbors BRAF, NRAS, or KIT mutations which influence both tumor development and treatment strategies. For example, it is still controversial whether adjuvant anti-PD-1 monotherapy or BRAF/MEK inhibitors may better improve the survival for resected BRAF-mutant melanoma. Furthermore, outcomes for melanoma with NRAS and KIT mutation receiving adjuvant immunotherapy remain unclear. METHODS: One hundred seventy-four stage III melanoma patients who underwent radical surgery in Fudan University Shanghai Cancer Center (FUSCC) during January 2017 to December 2021 were included in this real-world study. Patients were followed up until death or May 30th, 2022. Pearson's chi-squared test or Fisher's exact test was performed for univariable analysis of the different category groups. Log-rank analysis was used to identify the prognostic factors for disease-free survival (DFS). RESULTS: There were 41 (23.6%) patients with BRAF mutation, 31 (17.8%) with NRAS mutation, 17 (9.8%) with KIT mutation, and 85 (48.9%) wild-type patients without either genomic alteration of those three genes. Most ( n = 118, 67.8%) of them were acral melanoma, while 45 (25.9%) were cutaneous subtype, and 11 were (6.3%) primary unknown. Among them, 115 (66.1%) patients received pembrolizumab or toripalimab monotherapy as adjuvant therapy; 22 (12.6%) patients received high-dose interferon (IFN), and 37 (21.3%) patients were just for observation. There was no statistical difference in clinicopathologic factors between anti-PD-1 group and IFN/OBS group. Of all the enrolled patients, anti-PD-1 group had a better DFS than IFN/OBS group ( p = 0.039). In anti-PD-1 group, patients with BRAF or NRAS mutations had poorer DFS than wild-type group. No survival difference was found among patients harboring different gene mutations in IFN/OBS group. In wild-type patients, anti-PD-1 group had a better DFS than IFN/OBS group ( p = 0.003), while no survival benefits were found for patients with BRAF, NRAS, or KIT mutations. CONCLUSION: Although anti-PD-1 adjuvant therapy provides a better DFS in the general population and in wild-type patients, patients with BRAF, KIT or, especially, NRAS mutation may not benefit further from immunotherapy than conventional IFN treatment or observation.

Survival impact of immediate complete lymph node dissection for Chinese acral and cutaneous melanoma with micrometastasis in sentinel nodes: a retrospective study.

Sentinel node biopsy (SNB) has become a critical part of standard surgical treatment for melanoma with no clinical metastatic evidence. However, for patients with a positive sentinel node, the MSLT-II and DeCOG-SLT trials have shown that immediate complete lymph node dissection (CLND) does not bring further survival benefits. There is still an argument among the Chinese population dominated by acral subtypes on whether CLND can be omitted. Thus, this study aims to investigate the impact of immediate CLND on relapse-free survival (RFS) in Chinese melanoma patients with a positive sentinel node. Patients with acral or cutaneous melanoma of clinical Stages I-II who received SNB procedure and were detected with nodal micrometastasis were retrospectively collected at Fudan University Cancer Center (FUSCC) from January 2017 to December 2021. The clinicopathologic features and prognostic factors for RFS were analyzed. Out of 381 patients who received SNB in the past 5 years, 130 (34%) cases with SN micrometastasis detected were included in this study. Ninety-nine patients underwent immediate CLND while the other 31 patients received observation alone. Among patients who received CLND, the non-SN(NSN)-positive rate was 22.2%. Most of the clinicopathologic factors were balanced well between the CLND and non-CLND groups. However, more patients in the CLND group were detected with BRAF and NRAS mutation (P = 0.006) and received adjuvant PD-1 monotherapy (P = 0.042) as well. There were slightly fewer N1 patients in the CLND group, although the difference did not reach statistical significance (P = 0.075). The study found no significant difference in RFS between the two groups (P = 0.184). Even for patients with the acral subtype (P = 0.925), primary T4 lesion (P = 0.769), or presence of ulceration (P = 0.249), immediate CLND did not bring more survival benefits. Immediate CLND did not bring further RFS benefit for Chinese melanoma patients with SN micrometastasis in real-world clinical practice, even for patients with acral subtype or more tumor burden such as thick Breslow invasion and ulceration.