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Background and purpose: Surgery alone is not enough to get satisfied outcome for locally high-risk soft tissue sarcoma (STS). We retrospectively assessed the short-term efficacy and safety of preoperative radiotherapy followed by surgery in patients with locally high-risk STS. Methods: Data from consecutive patients treated with preoperative radiotherapy at Fudan University Shanghai Cancer Center from February 2021 to June 2022 were reviewed. The data included clinical characteristics, radiotherapy regimes, radiological images and pathology slides. The target volumes of radiotherapy were delineated on computed tomography (CT) simulation images with reference to fused magnetic resonance imaging (MRI) images slides by slides. All the patients received radiotherapy planned with intensity-modulated radiotherapy (IMRT). Counting data was presented as percentages. The rates of radiological response (complete response, partial response, stable disease, progressive disease, objective response and disease control), pathological response [near-pathologic complete response (near-pCR), defined as ≥90% non-viable tumor cells] and toxicities (acute skin toxicity and major wound complications occurring within 120 d of surgery) were analyzed. Results: Forty-one patients received radiotherapy before surgery, among them 33 patients were eligible: 31 for radiological assessment and 28 for pathological assessment. The median age was 53 years. Thirty (90.0%) cases were histologically classified as Grade 3. Six (19.4%) patients achieved partial response, and 1 patient had progressive disease after radiotherapy. None got complete response. The objective response rate was 19.4%, and the disease control rate was 96.8%. Near-pCR was found in 8 (28.6%) patients. Excluding patients receiving chemotherapy previously, the near-pCR rate was 34.8% (8/23). Grade 1 and 2 skin injuries were found on 33.3% (11/33) and 3.0% (1/33) patients. No grade 3 and 4 skin injury occurred. Major wound complications within 120 d of surgery occured in 1 (3.3%) patient. Conclusion: Preoperative radiotherapy facilitated with fused MRI images and IMRT has good short-term efficacy and tolerable acute toxicities for locally high-risk STS.

Background and purpose: For cutaneous and acral malignant melanoma, sentinel lymph node biopsy (SLNB) is an effective tool to evaluate the situation of regional lymph node metastasis and to determine the pathological stage. As an important part of the standard procedure for surgical diagnosis and treatment, SLNB has been recommended in major guidelines and already has a ten-year clinical application. Since the introduction of targeted therapy and immune therapy for malignant melanoma in 2017, the prognosis of patients has been significantly improved. This study aimed to collect the clinical data of Chinese malignant melanoma cases in recent five years so as to discover, in the era of new drug treatment, the significance of sentinel lymph node (SLN) status in clinical application and its influence on survival outcome. Methods: Data of 381 patients with histologically diagnosed malignant melanoma were retrospectively collected from 2017 to 2021 in Fudan University Shanghai Cancer Center. SLNB was performed with wide resection of the primary lesion for each case, and follow-ups of at least 6 months were taken afterwards. Lymphoscintigraphy or methylene blue dye was applied for identification of SLN. Results: A total of 381 patients were included. The mean Breslow thickness was 3.10 mm, among the 381 patients, 69.8% with acral lesion, 59.7% with ulceration, 34.6% with positive SLN, and the median relapse-free survival (RFS) was 17 months. Patient’s survival was significantly influenced by SLN status. Patients with more than 2 biopsied SLN had significantly better RFS in subgroups of N1a stage and T4 stage. There was no significant difference in RFS between patients who received complete lymph node dissection (CLND) and those who did no, and the latter even showed better RFS in subgroups of SLN biopsied number >2 and SLN micrometastasis diameter

Background and purpose: The prognosis of malignant melanoma (MM) in China and Asia is significantly worse than that of European and American populations, mainly because acral melanoma (AM) is inferior to cutaneous melanoma (CM) in terms of biological behavior, clinical features, prognosis, and efficacy of drugs (mainly immunotherapy). Certain changes have occurred in the last 5 years in the choice of surgical and drug-adjuvant treatment for MM. This study retrospectively analyzed the survival outcomes of Chinese CM and AM patients after surgical treatment in a single cancer center for the past five years. Methods:Data of melanoma patients undergoing surgical treatment were retrospectively collected from 2017 to 2021 in Fudan University Shanghai Cancer Center. The basic clinical characteristics, pathological features, lymph node tumor burden and survival information were carefully collected from medical document. Patients with mucosal subtype, unknown primary sites, or follow-up less than 6 months were excluded. Survival analysis and multivariable Cox regression analysis were performed to explore prognosis and associated risk factors. Results:Totally 585 patients were enrolled, including 397 AM and 188 CM patients. The median age was 59 (19-89) years, and 54% were female. AM and CM patients differed in gender, age, primary tumor location, gene mutation distribution and adjuvant therapy, but not in tumor burden associated factors including the Breslow thickness, ulceration and lymph node involvment. The median follow-up time was 24 months, and the median relapse-free survival (mRFS) was 36 months, with 1-year and 2-year RFS of 75.6% and 61.2%, respectively. However, there was no statistically significant difference in prognosis between the two subtypes. Primary ulceration (HR=2.265, 95% CI: 1.257-4.080), NRAS mutation (HR=1.816, 95% CI: 1.211-2.725) and advanced N stage (HR of N1, N2 and N3 versus N0 were 1.850, 4.085 and 4.191, respectively) were independent prognostic risk factors for RFS in AM; while the protective factors were female (HR=0.636, 95% CI: 0.433-0.933) and upper extremity primary lesions (HR=0.259, 95% CI: 0.105-0.639). Independent risk factors for RFS in CM included primary ulceration (HR=4.073, 95% CI: 1.718-9.654), and later N stage (HR=5.482, 95% CI: 2.385-12.601 for N3 stage). Conclusion: High tumor burden of primay lesion still deteriorates overall outcomes for both AM and CM, while harboring NRAS mutation might suggest even worse outcome for AM.

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. [ABSTRACT FROM AUTHOR]