scholarly journals Role of debulking surgery in combination with immune therapy: A successfully treated case of locally advanced mucosal melanoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Takahiro Kimura ◽  
Takayuki Takahama ◽  
Tomoko Wakasa ◽  
Shiori Adachi ◽  
Yusaku Akashi ◽  
...  
2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21517-e21517
Author(s):  
Xin Liu ◽  
Shiyu Jiang ◽  
Xiaowei Zhang ◽  
Feng Jin ◽  
Jun Cao ◽  
...  

e21517 Background: Mucosal melanoma is rare and has distinct clinical and genetic features. Even with advances in targeted and immune therapy, the survival of patients with advanced or recurrent mucosal melanomas remains poor. The standard treatment remains controversial and we conducted this real-world study aimed to test continuous intravenous Endostar infusion plus chemotherapy in patients with advanced or recurrent mucosal melanoma in the first-line setting. Methods: In total, all 43 patients with advanced or recurrent mucosal melanoma treated at Fudan University Shanghai Cancer Center between April 2017 and August 2020 were retrospectively included. Patients received dacarbazine plus cisplatin or temozolomide plus cisplatin regimens per the investigators’ preference. Endostar (105 mg/m2) was administered with continuous infusion for 168 hours (Civ 168h). Results: Of the 43 patients, 72.1% had metastatic disease, and 27.9% had locally advanced disease. The most common primary site was the gastrointestinal tract (51.2%), followed by the sinonasal tract (32.6%) and genitourinary tract (14.0%). The most commonly observed mutation was NRAS (23.1%), followed by BRAF (7.7%) and CKIT (5.1%). An objective response was observed in 12 (30.0%) of the 40 evaluable patients, and disease control was achieved in 31 (77.5%) patients. With a median follow-up of 17.6 months, the median progression-free survival (PFS) and overall survival (OS) were 4.9 and 15.3 months, respectively. Multivariate analysis indicated a high lymphocyte-to-monocyte ratio (LMR) was significantly correlated with favorable PFS (p = 0.012, hazard ratio [HR] 0.28, 95% CI: 0.10-0.76). Additionally, a high LMR (p = 0.023, HR 0.29, 95% CI: 0.10-0.84) and BRAF/KIT/RAS mutation (p = 0.028, HR 0.24, 95% CI: 0.07-0.86) were independently correlated with prolonged OS. Toxicity was manageable overall. Conclusions: Continuous Endostar infusion in combination with chemotherapy was effective and safe for the treatment of advanced or recurrent mucosal melanoma. Additionally, a high LMR was correlated with favorable PFS and OS in this patient population.


2020 ◽  
Vol 27 ◽  
Author(s):  
Ramarao Malla ◽  
Mohammad Amjad Kamal

: Cervical cancer (CC) is the fourth leading cancer in women in the age group 15-44 globally. Experimental as well as epidemiological studies identified that type16 and 18 HPV cause 70% of precancerous cervical lesions as well as cervical cancer worldwide by bringing about genetic as well as epigenetic changes in the host genome. The insertion of the HPV genome triggers various defense mechanisms including the silencing of tumor suppressor genes as well as activation of oncogenes associated with cancer metastatic pathway. E6 and E7 are small oncoproteins consisting of 150 and 100 amino acids respectively. These oncoproteins affect the regulation of the host cell cycle by interfering with p53 and pRb. Further these oncoproteins adversely affect the normal functions of the host cell by binding to their signaling proteins. Recent studies demonstrated that E6 and E7 oncoproteins are potential targets for CC. Therefore, this review discusses the role of E6 and E7 oncoproteins in metastasis and drug resistance as well as their regulation, early oncogene mediated signaling pathways. This review also uncovers the recent updates on molecular mechanisms of E6 and E7 mediated phytotherapy, gene therapy, immune therapy, and vaccine strategies as well as diagnosis through precision testing. Therefore, understanding the potential role of E6/E7 in metastasis and drug resistance along with targeted treatment, vaccine, and precision diagnostic strategies could be useful for the prevention and treatment of cervical cancer.


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1468
Author(s):  
Damiënne Marcus ◽  
Relinde I. Y. Lieverse ◽  
Carmen Klein ◽  
Amir Abdollahi ◽  
Philippe Lambin ◽  
...  

Radiotherapy (RT) has been shown to interfere with inflammatory signals and to enhance tumor immunogenicity via, e.g., immunogenic cell death, thereby potentially augmenting the therapeutic efficacy of immunotherapy. Conventional RT consists predominantly of high energy photon beams. Hypofractionated RT regimens administered, e.g., by stereotactic body radiation therapy (SBRT), are increasingly investigated in combination with cancer immunotherapy within clinical trials. Despite intensive preclinical studies, the optimal dose per fraction and dose schemes for elaboration of RT induced immunogenic potential remain inconclusive. Compared to the scenario of combined immune checkpoint inhibition (ICI) and RT, multimodal therapies utilizing other immunotherapy principles such as adoptive transfer of immune cells, vaccination strategies, targeted immune-cytokines and agonists are underrepresented in both preclinical and clinical settings. Despite the clinical success of ICI and RT combination, e.g., prolonging overall survival in locally advanced lung cancer, curative outcomes are still not achieved for most cancer entities studied. Charged particle RT (PRT) has gained interest as it may enhance tumor immunogenicity compared to conventional RT due to its unique biological and physical properties. However, whether PRT in combination with immune therapy will elicit superior antitumor effects both locally and systemically needs to be further investigated. In this review, the immunological effects of RT in the tumor microenvironment are summarized to understand their implications for immunotherapy combinations. Attention will be given to the various immunotherapeutic interventions that have been co-administered with RT so far. Furthermore, the theoretical basis and first evidences supporting a favorable immunogenicity profile of PRT will be examined.


Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3711
Author(s):  
François Montagne ◽  
Florian Guisier ◽  
Nicolas Venissac ◽  
Jean-Marc Baste

Non-small cell lung cancers (NSCLC) are different today, due to the increased use of screening programs and of innovative systemic therapies, leading to the diagnosis of earlier and pre-invasive tumors, and of more advanced and controlled metastatic tumors. Surgery for NSCLC remains the cornerstone treatment when it can be performed. The role of surgery and surgeons has also evolved because surgeons not only perform the initial curative lung cancer resection but they also accompany and follow-up patients from pre-operative rehabilitation, to treatment for recurrences. Surgery is personalized, according to cancer characteristics, including cancer extensions, from pre-invasive and local tumors to locally advanced, metastatic disease, or residual disease after medical treatment, anticipating recurrences, and patients’ characteristics. Surgical management is constantly evolving to offer the best oncologic resection adapted to each NSCLC stage. Today, NSCLC can be considered as a chronic disease and surgery is a valuable tool for the diagnosis and treatment of recurrences, and in palliative conditions to relieve dyspnea and improve patients’ comfort.


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