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Jun Guo - One of the best experts on this subject based on the ideXlab platform.
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Abstract IA16: The landscape of Mucosal Melanoma: A long way to go
Cancer Research, 2020Co-Authors: Jun GuoAbstract:Mucosal Melanoma is a rare disease, accounting for approximately 1.4% of all Caucasians’ Melanomas and 22% of Asian Melanomas, which are commonly found in the nasal cavity or sinuses, anorectum, and vulvovagina. Nearly half of the Mucosal Melanomas are amelanotic. The most common sites of metastatic disease are the liver and the lungs. The prognosis may be similar regardless of anatomic site of origin. The genetics of Mucosal Melanoma thatg originates from melanocytes within Mucosal epithelia has not been fully explored. Data suggest BRAF may occur in only 3–15% of all cases of Mucosal Melanoma. Mutations in KIT can be identified in 7–17% of all patients with Mucosal Melanoma. As to the adjuvant therapy, the only published randomized evidence supporting adjuvant therapy after resection of Mucosal Melanoma was from Lian et al. They randomized 189 patients with resected Mucosal Melanoma to observation, 1 year of high-dose IFN-α2b, or thrice-weekly chemotherapy with temozolomide plus cisplatin for six cycles. Adjuvant therapy was associated with a trend toward improved survival and HDI was less effective than temozolomide-based chemotherapy for patients with resected Mucosal Melanoma in respect to RFS. The preliminary interim analysis of a phase III trial (NCT03435302) of 204 patients with Mucosal Melanoma comparing temozolomide-based chemotherapy with HDI showed that the chemo was superior to HDI. Several clinical trials on adjuvant therapy of Mucosal Melanomas are ongoing, including NCT03178123 (a phase III trial of PD-1 inhibitors VS HDI) and NCT03241186 (phase II trial of nivolumab + ipilimumab). The clinical trials for systemic treatment of unresectable or metastatic Mucosal Melanoma were limited. A pooled analysis of the outcomes of patients with metastatic Mucosal Melanoma treated in trials either with single-agent nivolumab or the combination of ipilimumab and nivolumab compared outcomes to those of patients with cutaneous Melanoma. The ORR for Mucosal Melanoma receiving nivolumab monotherapy or nivolumab combined with ipilimumab were lower than cutaneous Melanoma, 23.3% vs. 40.9%, 37.1% vs. 60.4%. PD-1 monoclonal antibody was less effective in Mucosal Melanomas maybe because of low PD-L1 expression and tumor mutation burden (TMB). At the 2018 ASCO meeting, the results of phase II study of JS001 (PD-1 inhibitors) were reported. 128 Melanoma patients were enrolled. Subgroup analysis showed that patients with Mucosal origin were less effective (Mucosal 0%). How to increase the efficacy for the Mucosal Melanoma? As we all know, liver metastases are common in Mucosal Melanomas and difficult to handle. A phase Ic study of oncolytic virus (OrienX010) injected into liver metastases demonstrated good tolerance and efficacy in Chinese patients. The next step is to combine oncolytic virus injected into liver lesions with PD-1 antibody to improve the efficacy of liver metastasis. On the other hand, TKIs are found to have an influence on microenvironment in tumor and facilitate immunotherapy. We conducted a phase Ib study of JS001 in combination with axitinib in metastatic Mucosal Melanoma. The results were reported in ASCO 2018, which were encouraging to achieve ORR of 66.7%. Recurrent activating mutations in KIT have been identified in 15% of patients, but KIT inhibitors have not produced durable clinical responses. Patients with Mucosal Melanoma have a poor prognosis in part due to the lack of targeted therapies. Imatinib may remain the first-choice treatment option for patients with a KIT mutation. For Mucosal Melanoma patients, there is still a long way to go. Citation Format: Jun Guo. The landscape of Mucosal Melanoma: A long way to go [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr IA16.
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frequent genetic aberrations in the cell cycle related genes in Mucosal Melanoma indicate the potential for targeted therapy
Journal of Translational Medicine, 2019Co-Authors: Zhiyuan Cheng, Jun Guo, Chuanliang Cui, Yan KongAbstract:Melanoma is one of the most aggressive cancers with extremely poor prognosis, and the median survival time for stage IV patients is approximately 6 to 8 months. Unlike cutaneous Melanoma, Mucosal Melanoma is a rare Melanoma subtype among Caucasian patients but its incidence remains as high as 22.6% among Chinese patients. Screening specific genetic variations is the guideline to select targeted drugs for the treatment of advanced Melanoma, whereas the genetic variation spectrum and potential therapeutic targets for Mucosal Melanoma are largely unclear. It is urgent to identify promising genetic variants for Mucosal Melanoma so as to develop effective targeted therapies for this disease. Tumor samples from 213 Chinese Mucosal Melanoma patients were involved in this study. P16INK4a/Cyclin D1/CDK4 copy number was examined using the QuantiGene Plex DNA assay and the correlation between abnormal copy number and clinicopathological parameters was analyzed. Patient-derived xenograft models (PDX) were performed to detect the effects of CDK4/6 inhibitors on the proliferation of Mucosal Melanoma cells with altered copy number of CDK4 pathway (CDK4, Cyclin D1 and P16INK4a). The molecular mechanisms of CDK4/6 inhibitors on the proliferation of Mucosal Melanoma were analyzed by RNAseq. Among the 213 samples, the amplification rate of CDK4 and CCND1 was 47.0% and 27.7%, respectively, and the deletion rate of P16INK4a was 57.7%. Patients with more than one genetic abnormality were up to 81.7%. CDK4 pathway gene copy number variation was not associated with the prognosis of patients with Mucosal Melanoma (P > 0.05). Drug sensitivity tests showed that AT7519, a broad-spectrum CDK inhibitor, and PD0332991, a specific CDK4/6 inhibitor, exhibited higher inhibitory effect on CDK4 signaling pathway abnormal Mucosal Melanoma cells-derived PDX tumors growth than CDK4 signaling pathway normal ones. RNA-seq analysis showed that CDK4 inhibitors may affect tumor proliferation through multiple signaling pathways. Abnormal copy number of cell cycle related genes is frequently found in Mucosal Melanoma. CDK4/6 inhibitors significantly suppress the PDX tumor growth with abnormal CDK4 pathway. CDK4 signaling variations predict the effectiveness of CDK4 inhibitors in Mucosal Melanoma.
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Genotyping of Mucosal Melanoma.
Chinese clinical oncology, 2014Co-Authors: Lu Si, Xuan Wang, Jun GuoAbstract:Mucosal Melanoma is rare and associated with extremely poor prognosis. Mucosal Melanoma has historically been refractory to traditional therapeutic approaches. Recently molecularly based targeted drugs show great success in Melanoma. The success of these drug strategies can be partially attributed to the identification of the genetic alterations responsible for the development and progression of metastatic Melanoma. This review will focus on genes involved in two major Mucosal Melanoma-related signaling pathways, the RAS/RAF/mitogen activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinases (PI3K)-AKT pathway, and detail the current understanding of their roles in Melanoma progression. Additional mutations in key genes, such as KIT, GNAQ and MITF, in Mucosal Melanoma will also be introduced. Finally, an overview of the current targeted therapy landscape will be provided.
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Adjuvant therapy of Mucosal Melanoma.
Chinese clinical oncology, 2014Co-Authors: Bin Lian, Jun GuoAbstract:Mucosal Melanoma is a rare subtype of Melanoma and associated with extremely poor prognosis. However, standard adjuvant therapy for Mucosal Melanoma has not been established. Some approaches have been studied to reduce the risk of recurrence in patients. These include adjuvant chemotherapy, immunotherapy, targeted therapy, and radiotherapy (RT). In this review we aim to summarize and evaluate the therapies in development.
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Treatment algorithm of metastatic Mucosal Melanoma.
Chinese clinical oncology, 2014Co-Authors: Xuan Wang, Jun GuoAbstract:Mucosal Melanoma is usually considered as the most aggressive and treatment-resistant subtype of Melanoma. The unsatisfactory results of standard clinical therapies for metastatic Melanoma highlight the needs for effective new therapeutic strategies. Recent successes in the development of new therapies for metastatic Melanoma, such as inhibitors for mitogen-activated protein kinase (MAPK) pathway and blocking antibodies against cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) or programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway, have yielded promising results, expanding the continually evolving landscape of therapeutic options for patients with this disease. In this chapter we review chemotherapies, immunotherapies, targeted therapies and angiogenesis therapies in metastatic Mucosal Melanoma and discuss their implications.
Chuanliang Cui - One of the best experts on this subject based on the ideXlab platform.
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frequent genetic aberrations in the cell cycle related genes in Mucosal Melanoma indicate the potential for targeted therapy
Journal of Translational Medicine, 2019Co-Authors: Zhiyuan Cheng, Jun Guo, Chuanliang Cui, Yan KongAbstract:Melanoma is one of the most aggressive cancers with extremely poor prognosis, and the median survival time for stage IV patients is approximately 6 to 8 months. Unlike cutaneous Melanoma, Mucosal Melanoma is a rare Melanoma subtype among Caucasian patients but its incidence remains as high as 22.6% among Chinese patients. Screening specific genetic variations is the guideline to select targeted drugs for the treatment of advanced Melanoma, whereas the genetic variation spectrum and potential therapeutic targets for Mucosal Melanoma are largely unclear. It is urgent to identify promising genetic variants for Mucosal Melanoma so as to develop effective targeted therapies for this disease. Tumor samples from 213 Chinese Mucosal Melanoma patients were involved in this study. P16INK4a/Cyclin D1/CDK4 copy number was examined using the QuantiGene Plex DNA assay and the correlation between abnormal copy number and clinicopathological parameters was analyzed. Patient-derived xenograft models (PDX) were performed to detect the effects of CDK4/6 inhibitors on the proliferation of Mucosal Melanoma cells with altered copy number of CDK4 pathway (CDK4, Cyclin D1 and P16INK4a). The molecular mechanisms of CDK4/6 inhibitors on the proliferation of Mucosal Melanoma were analyzed by RNAseq. Among the 213 samples, the amplification rate of CDK4 and CCND1 was 47.0% and 27.7%, respectively, and the deletion rate of P16INK4a was 57.7%. Patients with more than one genetic abnormality were up to 81.7%. CDK4 pathway gene copy number variation was not associated with the prognosis of patients with Mucosal Melanoma (P > 0.05). Drug sensitivity tests showed that AT7519, a broad-spectrum CDK inhibitor, and PD0332991, a specific CDK4/6 inhibitor, exhibited higher inhibitory effect on CDK4 signaling pathway abnormal Mucosal Melanoma cells-derived PDX tumors growth than CDK4 signaling pathway normal ones. RNA-seq analysis showed that CDK4 inhibitors may affect tumor proliferation through multiple signaling pathways. Abnormal copy number of cell cycle related genes is frequently found in Mucosal Melanoma. CDK4/6 inhibitors significantly suppress the PDX tumor growth with abnormal CDK4 pathway. CDK4 signaling variations predict the effectiveness of CDK4 inhibitors in Mucosal Melanoma.
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Postoperative radiotherapy in resected sinonasal Mucosal Melanoma.
Journal of Clinical Oncology, 2019Co-Authors: Li Zhou, Xuan Wang, Bin Lian, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Yan Kong, Lili Mao, Xieqiao YanAbstract:e21059Background: Mucosal Melanoma is rare but highly aggressive. Sinonasal Melanoma comprised approximately 26% of the whole Mucosal Melanoma. Complete surgery plus postoperative radiotherapy is o...
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Mucosal Melanoma staging and classification: Firstly established.
Journal of Clinical Oncology, 2019Co-Authors: Bin Lian, Li Zhou, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Xin Song, Xiaoshi Zhang, Lili MaoAbstract:e21008Background: Mucosal Melanomas (MM) have a significantly worse survival outcome than cutaneous Melanoma. The current staging rules for cutaneous Melanoma do not apply to Mucosal Melanoma. Our ...
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Chemotherapy, biochemotherapy and anti-VEGF therapy in metastatic Mucosal Melanoma
Chinese clinical oncology, 2014Co-Authors: Chuanliang Cui, Bixia Tang, Jun GuoAbstract:Mucosal Melanomas arise from melanocytes located at various Mucosal membranes, which demonstrate a clear demographic and ethnic disparity. This subtype of Melanoma has more aggressive course and poorer prognosis than other subsets of Melanomas. Due to their rarity, there is no well-established protocol of staging and treatment of Mucosal Melanomas. Significant advances have been achieved in novel immunotherapeutic and specific targeted agents for metastatic Melanomas. For Mucosal Melanoma patients especially without known gene mutation, anti-angiogenic therapy combined with chemotherapy or other targeted drugs has shown promising efficacy, either as first- or second-line treatment. In some subset analysis, patients with Mucosal Melanoma, harboring wild type BRAF , might get more clinical and survival benefits than cutaneous ones. Therefore it is rational to further study these therapeutic strategies in the group of Mucosal Melanoma. Chemotherapy or biochemotherapy only showed limited efficacy without significant survival improvement, but larger sample size study is still required. Herein we presented a comprehensive review of chemotherapy/biochemotherapy and anti-vascular endothelial growth factor (anti-VEGF) therapy in metastatic Mucosal Melanoma.
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phase ii randomized trial comparing high dose ifn α2b with temozolomide plus cisplatin as systemic adjuvant therapy for resected Mucosal Melanoma
Clinical Cancer Research, 2013Co-Authors: Bin Lian, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Yan Kong, Lili Mao, Bixia Tang, Jun GuoAbstract:Purpose: Mucosal Melanoma is rare and associated with extremely poor prognosis. However, standard adjuvant therapy for Mucosal Melanoma has not been established. We conducted a randomized phase II clinical trial in patients with resected Mucosal Melanoma to compare the efficacy and safety of high-dose IFN-α2b (HDI) and temozolomide-based chemotherapy as adjuvant therapy. Experimental Design: Patients with Mucosal Melanoma in stage II/III after surgery were randomized into three groups: observation group (group A, surgery alone), HDI group (group B, treated with 15 × 10 6 U/m 2 /d IFN-α2b, followed by 9 × 10 6 U IFN-α2b), and temozolomide (200 mg/m 2 /d) plus cisplatin (75 mg/m 2 ) group (group C). The endpoints were relapse-free survival (RFS), overall survival (OS), and toxicities. Results: One hundred and eighty-nine patients were enrolled and finally analyzed. With a median follow-up of 26.8 months, the median RFS was 5.4, 9.4, and 20.8 months for group A, B, and C, respectively. Estimated median OS for group A, B, and C was 21.2, 40.4, and 48.7 months, respectively. Patients treated with temozolomide plus cisplatin showed significant improvements in RFS ( P P Conclusion: Both temozolomide-based chemotherapy and HDI are effective and safe as adjuvant therapies for resected Mucosal Melanoma as compared with observation alone. However, HDI tends to be less effective than temozolomide-based chemotherapy for patients with resected Mucosal Melanoma in respect to RFS. The temozolomide plus cisplatin regimen might be a better choice for patients with resected Mucosal Melanoma. Clin Cancer Res; 19(16); 4488–98. ©2013 AACR .
Bin Lian - One of the best experts on this subject based on the ideXlab platform.
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Mucosal Melanoma staging and classification: Firstly established.
Journal of Clinical Oncology, 2019Co-Authors: Bin Lian, Li Zhou, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Xin Song, Xiaoshi Zhang, Lili MaoAbstract:e21008Background: Mucosal Melanomas (MM) have a significantly worse survival outcome than cutaneous Melanoma. The current staging rules for cutaneous Melanoma do not apply to Mucosal Melanoma. Our ...
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Postoperative radiotherapy in resected sinonasal Mucosal Melanoma.
Journal of Clinical Oncology, 2019Co-Authors: Li Zhou, Xuan Wang, Bin Lian, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Yan Kong, Lili Mao, Xieqiao YanAbstract:e21059Background: Mucosal Melanoma is rare but highly aggressive. Sinonasal Melanoma comprised approximately 26% of the whole Mucosal Melanoma. Complete surgery plus postoperative radiotherapy is o...
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Adjuvant therapy of Mucosal Melanoma.
Chinese clinical oncology, 2014Co-Authors: Bin Lian, Jun GuoAbstract:Mucosal Melanoma is a rare subtype of Melanoma and associated with extremely poor prognosis. However, standard adjuvant therapy for Mucosal Melanoma has not been established. Some approaches have been studied to reduce the risk of recurrence in patients. These include adjuvant chemotherapy, immunotherapy, targeted therapy, and radiotherapy (RT). In this review we aim to summarize and evaluate the therapies in development.
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phase ii randomized trial comparing high dose ifn α2b with temozolomide plus cisplatin as systemic adjuvant therapy for resected Mucosal Melanoma
Clinical Cancer Research, 2013Co-Authors: Bin Lian, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Yan Kong, Lili Mao, Bixia Tang, Jun GuoAbstract:Purpose: Mucosal Melanoma is rare and associated with extremely poor prognosis. However, standard adjuvant therapy for Mucosal Melanoma has not been established. We conducted a randomized phase II clinical trial in patients with resected Mucosal Melanoma to compare the efficacy and safety of high-dose IFN-α2b (HDI) and temozolomide-based chemotherapy as adjuvant therapy. Experimental Design: Patients with Mucosal Melanoma in stage II/III after surgery were randomized into three groups: observation group (group A, surgery alone), HDI group (group B, treated with 15 × 10 6 U/m 2 /d IFN-α2b, followed by 9 × 10 6 U IFN-α2b), and temozolomide (200 mg/m 2 /d) plus cisplatin (75 mg/m 2 ) group (group C). The endpoints were relapse-free survival (RFS), overall survival (OS), and toxicities. Results: One hundred and eighty-nine patients were enrolled and finally analyzed. With a median follow-up of 26.8 months, the median RFS was 5.4, 9.4, and 20.8 months for group A, B, and C, respectively. Estimated median OS for group A, B, and C was 21.2, 40.4, and 48.7 months, respectively. Patients treated with temozolomide plus cisplatin showed significant improvements in RFS ( P P Conclusion: Both temozolomide-based chemotherapy and HDI are effective and safe as adjuvant therapies for resected Mucosal Melanoma as compared with observation alone. However, HDI tends to be less effective than temozolomide-based chemotherapy for patients with resected Mucosal Melanoma in respect to RFS. The temozolomide plus cisplatin regimen might be a better choice for patients with resected Mucosal Melanoma. Clin Cancer Res; 19(16); 4488–98. ©2013 AACR .
Yan Kong - One of the best experts on this subject based on the ideXlab platform.
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frequent genetic aberrations in the cell cycle related genes in Mucosal Melanoma indicate the potential for targeted therapy
Journal of Translational Medicine, 2019Co-Authors: Zhiyuan Cheng, Jun Guo, Chuanliang Cui, Yan KongAbstract:Melanoma is one of the most aggressive cancers with extremely poor prognosis, and the median survival time for stage IV patients is approximately 6 to 8 months. Unlike cutaneous Melanoma, Mucosal Melanoma is a rare Melanoma subtype among Caucasian patients but its incidence remains as high as 22.6% among Chinese patients. Screening specific genetic variations is the guideline to select targeted drugs for the treatment of advanced Melanoma, whereas the genetic variation spectrum and potential therapeutic targets for Mucosal Melanoma are largely unclear. It is urgent to identify promising genetic variants for Mucosal Melanoma so as to develop effective targeted therapies for this disease. Tumor samples from 213 Chinese Mucosal Melanoma patients were involved in this study. P16INK4a/Cyclin D1/CDK4 copy number was examined using the QuantiGene Plex DNA assay and the correlation between abnormal copy number and clinicopathological parameters was analyzed. Patient-derived xenograft models (PDX) were performed to detect the effects of CDK4/6 inhibitors on the proliferation of Mucosal Melanoma cells with altered copy number of CDK4 pathway (CDK4, Cyclin D1 and P16INK4a). The molecular mechanisms of CDK4/6 inhibitors on the proliferation of Mucosal Melanoma were analyzed by RNAseq. Among the 213 samples, the amplification rate of CDK4 and CCND1 was 47.0% and 27.7%, respectively, and the deletion rate of P16INK4a was 57.7%. Patients with more than one genetic abnormality were up to 81.7%. CDK4 pathway gene copy number variation was not associated with the prognosis of patients with Mucosal Melanoma (P > 0.05). Drug sensitivity tests showed that AT7519, a broad-spectrum CDK inhibitor, and PD0332991, a specific CDK4/6 inhibitor, exhibited higher inhibitory effect on CDK4 signaling pathway abnormal Mucosal Melanoma cells-derived PDX tumors growth than CDK4 signaling pathway normal ones. RNA-seq analysis showed that CDK4 inhibitors may affect tumor proliferation through multiple signaling pathways. Abnormal copy number of cell cycle related genes is frequently found in Mucosal Melanoma. CDK4/6 inhibitors significantly suppress the PDX tumor growth with abnormal CDK4 pathway. CDK4 signaling variations predict the effectiveness of CDK4 inhibitors in Mucosal Melanoma.
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Postoperative radiotherapy in resected sinonasal Mucosal Melanoma.
Journal of Clinical Oncology, 2019Co-Authors: Li Zhou, Xuan Wang, Bin Lian, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Yan Kong, Lili Mao, Xieqiao YanAbstract:e21059Background: Mucosal Melanoma is rare but highly aggressive. Sinonasal Melanoma comprised approximately 26% of the whole Mucosal Melanoma. Complete surgery plus postoperative radiotherapy is o...
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phase ii randomized trial comparing high dose ifn α2b with temozolomide plus cisplatin as systemic adjuvant therapy for resected Mucosal Melanoma
Clinical Cancer Research, 2013Co-Authors: Bin Lian, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Yan Kong, Lili Mao, Bixia Tang, Jun GuoAbstract:Purpose: Mucosal Melanoma is rare and associated with extremely poor prognosis. However, standard adjuvant therapy for Mucosal Melanoma has not been established. We conducted a randomized phase II clinical trial in patients with resected Mucosal Melanoma to compare the efficacy and safety of high-dose IFN-α2b (HDI) and temozolomide-based chemotherapy as adjuvant therapy. Experimental Design: Patients with Mucosal Melanoma in stage II/III after surgery were randomized into three groups: observation group (group A, surgery alone), HDI group (group B, treated with 15 × 10 6 U/m 2 /d IFN-α2b, followed by 9 × 10 6 U IFN-α2b), and temozolomide (200 mg/m 2 /d) plus cisplatin (75 mg/m 2 ) group (group C). The endpoints were relapse-free survival (RFS), overall survival (OS), and toxicities. Results: One hundred and eighty-nine patients were enrolled and finally analyzed. With a median follow-up of 26.8 months, the median RFS was 5.4, 9.4, and 20.8 months for group A, B, and C, respectively. Estimated median OS for group A, B, and C was 21.2, 40.4, and 48.7 months, respectively. Patients treated with temozolomide plus cisplatin showed significant improvements in RFS ( P P Conclusion: Both temozolomide-based chemotherapy and HDI are effective and safe as adjuvant therapies for resected Mucosal Melanoma as compared with observation alone. However, HDI tends to be less effective than temozolomide-based chemotherapy for patients with resected Mucosal Melanoma in respect to RFS. The temozolomide plus cisplatin regimen might be a better choice for patients with resected Mucosal Melanoma. Clin Cancer Res; 19(16); 4488–98. ©2013 AACR .
Zhihong Chi - One of the best experts on this subject based on the ideXlab platform.
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Postoperative radiotherapy in resected sinonasal Mucosal Melanoma.
Journal of Clinical Oncology, 2019Co-Authors: Li Zhou, Xuan Wang, Bin Lian, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Yan Kong, Lili Mao, Xieqiao YanAbstract:e21059Background: Mucosal Melanoma is rare but highly aggressive. Sinonasal Melanoma comprised approximately 26% of the whole Mucosal Melanoma. Complete surgery plus postoperative radiotherapy is o...
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Mucosal Melanoma staging and classification: Firstly established.
Journal of Clinical Oncology, 2019Co-Authors: Bin Lian, Li Zhou, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Xin Song, Xiaoshi Zhang, Lili MaoAbstract:e21008Background: Mucosal Melanomas (MM) have a significantly worse survival outcome than cutaneous Melanoma. The current staging rules for cutaneous Melanoma do not apply to Mucosal Melanoma. Our ...
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Analysis of TSC1 mutation spectrum in Mucosal Melanoma.
Journal of cancer research and clinical oncology, 2017Co-Authors: Jie Dai, Huan Tang, Junya Yan, Zhihong ChiAbstract:Mucosal Melanoma is a relatively rare subtype of Melanoma for which no clearly established therapeutic strategy exists. The genes of the mTOR signalling pathway have drawn great attention as key targets for cancer treatment, including Melanoma. In this study, we aimed to investigate the mutation status of the upstream mTOR regulator TSC1 and evaluated its correlation with the clinicopathological features of Mucosal Melanoma. We collected 91 Mucosal Melanoma samples for detecting TSC1 mutations. All the coding exons of TSC1 were amplified by PCR and subjected to Sanger sequencing. Expression level of TSC1 encoding protein (hamartin) was detected by immunohistochemistry. The activation of mTOR pathway was determined by evaluating the phosphorylation status of S6RP and 4E-BP1. The overall mutation frequency of TSC1 was found to be 17.6% (16/91 patients). TSC1 mutations were more inclined to occur in advanced Mucosal Melanoma (stages III and IV). In the 16 patients with TSC1 mutations, 14 different mutations were detected, affecting 11 different exons. TSC1 mutations were correlated with upregulation of S6RP phosphorylation but were unrelated to 4E-BP1 phosphorylation or hamartin expression. Mucosal Melanoma patients with TSC1 mutations had a worse outcome than patients without TSC1 mutations (24.0 versus 34.0 months, P = 0.007). Our findings suggest that TSC1 mutations are frequent in Mucosal Melanoma. TSC1 mutations can activate the mTOR pathway through phospho-S6RP and might be a poor prognostic predictor of Mucosal Melanoma. Our data implicate the potential significance of TSC1 mutations for effective and specific drug therapy for Mucosal Melanoma.
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phase ii randomized trial comparing high dose ifn α2b with temozolomide plus cisplatin as systemic adjuvant therapy for resected Mucosal Melanoma
Clinical Cancer Research, 2013Co-Authors: Bin Lian, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Yan Kong, Lili Mao, Bixia Tang, Jun GuoAbstract:Purpose: Mucosal Melanoma is rare and associated with extremely poor prognosis. However, standard adjuvant therapy for Mucosal Melanoma has not been established. We conducted a randomized phase II clinical trial in patients with resected Mucosal Melanoma to compare the efficacy and safety of high-dose IFN-α2b (HDI) and temozolomide-based chemotherapy as adjuvant therapy. Experimental Design: Patients with Mucosal Melanoma in stage II/III after surgery were randomized into three groups: observation group (group A, surgery alone), HDI group (group B, treated with 15 × 10 6 U/m 2 /d IFN-α2b, followed by 9 × 10 6 U IFN-α2b), and temozolomide (200 mg/m 2 /d) plus cisplatin (75 mg/m 2 ) group (group C). The endpoints were relapse-free survival (RFS), overall survival (OS), and toxicities. Results: One hundred and eighty-nine patients were enrolled and finally analyzed. With a median follow-up of 26.8 months, the median RFS was 5.4, 9.4, and 20.8 months for group A, B, and C, respectively. Estimated median OS for group A, B, and C was 21.2, 40.4, and 48.7 months, respectively. Patients treated with temozolomide plus cisplatin showed significant improvements in RFS ( P P Conclusion: Both temozolomide-based chemotherapy and HDI are effective and safe as adjuvant therapies for resected Mucosal Melanoma as compared with observation alone. However, HDI tends to be less effective than temozolomide-based chemotherapy for patients with resected Mucosal Melanoma in respect to RFS. The temozolomide plus cisplatin regimen might be a better choice for patients with resected Mucosal Melanoma. Clin Cancer Res; 19(16); 4488–98. ©2013 AACR .