scholarly journals A New Role of Vemurafenib as a Neoadjuvant Treatment of Axillary and Brain Melanoma Metastases

2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Idit Melnik ◽  
Michal Lotem ◽  
Boris Yoffe

Vemurafenib is approved by the FDA for the management of unresectable or metastatic melanoma. However, its role as a neoadjuvant therapy has not been determined. We present the first documented case in which vemurafenib induced complete tumor necrosis of both lymph node and brain metastases within one month or less, an outcome that indicated that the patient was a good candidate for excisional surgery.

2021 ◽  
Author(s):  
Ulrich Ronellenfitsch ◽  
Nika Maximov ◽  
Juliane Friedrichs ◽  
Jorg Kleeff

BACKGROUND The lymph node yield is an important surrogate parameter for assessing the oncological radicality of the resection of gastrointestinal carcinomas and a prognostic factor in these diseases. It remains unclear if and to what extent neoadjuvant chemotherapy, radiotherapy or chemoradiotherapy, which have become established treatments for carcinoma of the esophagus, stomach, and rectum and are increasingly used in pancreatic carcinoma, affect the lymph node yield. OBJECTIVE This systematic review with meta-analysis is conducted with the aim of summarizing the available evidence regarding the oncological surrogate marker lymph node yield in patients with gastrointestinal carcinomas undergoing surgery after neoadjuvant treatment compared to those operated without neoadjuvant therapy. METHODS Studies comparing oncological resection of esophageal, stomach, pancreatic and rectal carcinoma with and without prior neoadjuvant therapy are eligible for inclusion regardless of study design. Publications will be identified with a defined search strategy in the electronic databases PubMed and Cochrane Library. The primary endpoint of the analysis is the number of lymph nodes identified in the resected specimen. Secondary endpoints include number of harvested metastatic lymph nodes, operation time, postoperative complications, pTNM staging, and overall and recurrence-free survival time. Using suitable statistical methods, the endpoints between patients with and without neoadjuvant therapy as well as in defined subgroups (neoadjuvant chemotherapy, neoadjuvant radiotherapy, neoadjuvant chemoradiotherapy, and esophageal, gastric, pancreatic, and rectal cancer) will be compared. RESULTS As of October 2021, we started with the data collection. CONCLUSIONS This systematic review with meta-analysis is conducted with the aim of summarizing the available evidence regarding the oncological surrogate marker lymph node yield in patients with gastrointestinal carcinomas undergoing surgery after neoadjuvant treatment compared to those operated without neoadjuvant therapy. CLINICALTRIAL This systematic review is registered at PROSPERO, ID: 218459.


2016 ◽  
Vol 70 (7) ◽  
pp. 584-592 ◽  
Author(s):  
Zhaomin Xu ◽  
Mariana E Berho ◽  
Adan Z Becerra ◽  
Christopher T Aquina ◽  
Bradley J Hensley ◽  
...  

AimsLymph node yield (LNY) is used as a marker of adequate oncological resection. The American Joint Committee on Cancer (AJCC) currently recommends that at least 12 nodes are necessary to confirm node-negative disease for rectal cancer. A LNY of 12 is not always achieved, particularly in patients who have undergone neoadjuvant treatment. This study attempts to examine factors associated with LNY and its prognostic impact following neoadjuvant chemoradiation in rectal cancer.MethodsThe 2006–2011 National Cancer Data Base was queried for patients with clinical stage I–III rectal cancer who underwent a proctectomy. Suboptimal LNY was defined as <12 lymph nodes examined. A mixed-effects multinomial logistic regression model was used to identify independent factors associated with LNY. Mixed-effects Cox proportional hazards models were used to estimate the adjusted effect of LNY on 5-year overall survival.Results25 447 patients met inclusion criteria. Overall, 62% of the cohort received neoadjuvant chemoradiation and 32% had suboptimal LNY. The median LNY for patients who received neoadjuvant therapy was 13 (IQR: 9–18) and for patients who did not receive neoadjuvant therapy was 15 (IQR: 12–21). After risk adjustment, there was a 3.5-fold difference in the rate of suboptimal LNY among individual hospitals (27%–95%). Suboptimal LNY was independently associated with an 18% increased hazard of death among patients who did not receive neoadjuvant treatment and a 20% increased hazard of death among those who did receive neoadjuvant treatment when controlled for adjuvant treatment, staging, proximal/distal margins and other patient factors.ConclusionsSuboptimal LNY is independently associated with worse overall survival regardless of neoadjuvant therapy, pathological staging and patient factors in rectal cancer. This finding underlies the importance and challenge of an optimal lymph node evaluation for prognostication, especially for patients receiving neoadjuvant therapy.


2020 ◽  
Author(s):  
Thuy Thi Nguyen ◽  
Guillaume Gapihan ◽  
Pauline Tetu ◽  
Frédéric Pamoukdjian ◽  
Morad El Bouchtaoui ◽  
...  

Abstract Background: Melanoma brain metastases are the main cause of specific death among patients with metastatic melanoma. The biology of melanoma brain metastases remains largely to be deciphered, as there have been only a few genomic studies on brain metastatic samples. In this study, melanoma metastatic lymph nodes were used with the aim to identify biomarkers associated with the occurrence of brain metastases. Methods: Fifty-one patients with melanoma lymph node metastasis and a median follow-up of 48 months were included in the development cohort. Transcriptomic data were obtained from these metastatic lymph nodes and patients who developed brain metastases and those who did not were compared. Recommendations for tumour marker prognostic studies (REMARK recommendations) were followed.Results: From transcriptomic data, we identified PROM2 which was significantly overexpressed in metastatic lymph nodes of patients who developed brain metastases compared to those who did not. Using immunohistochemistry with two different anti-PROM2 antibodies, a PROM2 score was developed for metastatic lymph nodes. Using a cut-off of 5, a PROM2 mean score ≥5 was significantly associated with an increased risk of brain metastases and an increased hazard risk of death by 4.These results were confirmed in an internal validation cohort of 50 additional patients with melanoma lymph node metastases.Conclusions: In this study, we identified PROM2 expression as a biomarker predictive of the occurrence of distant metastases, particularly brain metastases, among patients with stage III melanoma. Our findings open new perspectives to validate PROM2 as a useful biomarker for clinical trials in the adjuvant setting, and as a potential biotarget for the treatment of metastatic melanoma.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16549-e16549
Author(s):  
Yuzhou Zhao ◽  
Guangsen Han ◽  
Jing Zhuang ◽  
Zhimeng Li ◽  
Gangcheng Wang ◽  
...  

e16549 Background: Neoadjuvant chemotherapy for patients with locally advanced gastric and gastroesophageal junction adenocarcinoma (GC/GEJC) can improve the overall survival without increasing operation risk. Nowadays, immunotherapy has become a new promising neoadjuvant treatment. Therefore, we intended to evaluate the safety and efficacy of camrelizumab (anti-PD-1 antibody) combined with FOLFOX as the neoadjuvant therapy for patients with locally advanced GC/GEJC who received D2 radical gastrectomy. Methods: Patients who were diagnosed as resectable locally advanced GC/GEJC received the neoadjuvant treatment of camrelizumab and FOLFOX every 2 weeks for 4 cycles. Imaging evaluation was performed in 2-4 weeks after neoadjuvant therapy. Patients who had no progression disease (PD) were recruited. Eligible patients underwent gastrectomy with D2 lymph node dissection through laparotomy or laparoscopic surgery. The primary end points were safety and R0 resection rate. Results: From July 24 2019 to January 31 2020, 15 patients were recruited. The mean age was 57 years. A total of 10(67%) were males and 5(33%) were females. According to AJCC 8th, cT3 and cT4 were confirmed in 7(47%) patients and 8(53%) patients, N1 and N2 in 7(47%) patients and 8(53%) patients, respectively. During operation, intraperitoneal metastases were found in 2 patients. Of the 13 surgeries, only 2 were laparoscopic and the others were laparotomy. The surgical procedures included Roux-en-Y (9, 69.2%), Billroth II (1, 7.7%) and jejunum interposition (3, 23.1%). Thirteen patients underwent gastrectomy with D2 lymph node dissection and all of them were confirmed R0 resection by postoperative pathology results. The mean lymph node yield was 44.1±13.2 nodes, positive lymph node yield was 1.8±2.8 nodes. Duration time of surgery was 186.5±45.5 minutes, mean blood loss was 219.2±109 ml during the operation. Mean hospital stays were 13.2±2.4 days. Only 1 patient experienced grade 3 pneumonia. Neither serious intraoperative complications nor immune-related adverse events both prior and post operation were observed. There was no treatment-related death. Conclusions: Camrelizumab combined with FLOFOX as neoadjuvant treatment for patients with locally advanced GC/GEJC showed acceptable toxicity and promising efficacy with low complications and mortality. Clinical trial information: NCT03939962 .


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Lihua Tang ◽  
Wei Zhang ◽  
Bing Su ◽  
Bo Yu

Metastatic melanoma, the primary cause of skin cancer-related death, warrants new therapeutic approaches that target the regulatory machinery at molecular level. While long noncoding RNAs (lncRNAs) are dysregulated in a number of cancer types, limited data are available on the expression and function of lncRNAs in melanoma metastasis. The primary objective of this study was to investigate the role of 6 metastasis-related lncRNAs in pairs of primary melanoma and matched lymph node metastatic tissues. Among the tested lncRNAs, HOTAIR was the most highly expressed in lymph node metastasis. The role of HOTAIR in melanoma cell motility and invasion was further evaluated by knocking down HOTAIR with siRNAs. Knockdown of HOTAIR resulted in the reduction of motility and invasion of human melanoma cell line A375, as assessed by wound healing assay and Matrigel-based invasion assay. siHOTAIR also suppressed the degradation of gelatin matrix, suggesting that HOTAIR promotes gelatinase activity. Together, our study shows that HOTAIR is overexpressed in metastatic tissue, which is associated with the ability of HOTAIR to promote melanoma cell motility and invasion. These data indicate that lncRNAs may be involved in the metastasis of melanoma and provide support for further evaluation of lncRNAs in melanoma.


2021 ◽  
Author(s):  
Shuguang Zhu ◽  
Haibo Li ◽  
Jianwen Zhang ◽  
Chunhui Qiu ◽  
Tianxing Dai ◽  
...  

Abstract Prognosis of ICC with lymph node metastasis is poor. And the feasibility of operation is uncertain, which is a contraindication in NCCN guidelines. In addition, in the neoadjuvant therapy of ICC, the role of immunotherapy is not clear. We describe a case of ICC with lymph node metastasis was successfully treated with neoadjuvant therapy.


Author(s):  
Eliza Hagens ◽  
Karina Tukanova ◽  
Sara Jamel ◽  
Mark van Berge Henegouwen ◽  
George B Hanna ◽  
...  

Summary Introduction The prognostic value of histomorphologic regression in primary esophageal cancer has been previously established, however the impact of lymph node (LN) response on survival still remains unclear. The aim of this review was to assess the prognostic significance of LN regression or downstaging following neoadjuvant therapy for esophageal cancer. Methods An electronic search was performed to identify articles evaluating LN regression or downstaging after neoadjuvant therapy. Random effects meta-analyses were performed to assess the influence of regression in the LNs and nodal downstaging on overall survival. Histomorphologic tumor regression in LNs was defined by the absence of viable cells or degree of fibrosis on histopathologic examination. Downstaged LNs were defined as pN0 nodes by the tumor, node, and metastasis classification, which were positive prior to treatment neoadjuvant. Results Eight articles were included, three of which assessed tumor regression (number of patients = 292) and five assessed downstaging (number of patients = 1368). Complete tumor regression (average rate of 29.1%) in the LNs was associated with improved survival, although not statistically significant (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.26–1.06; P = 0.17). LNs downstaging (average rate of 32.2%) was associated with improved survival compared to node positivity after neoadjuvant treatment (HR = 0.41, 95%CI = 0.22–0.77; P = 0.005). Discussion The findings of this meta-analysis have shown a survival benefit in patients with LN downstaging and are suggestive for considering LN downstaging to ypN0 as an additional prognostic marker in staging and in the comparative evaluation of differing neoadjuvant regimens in clinical trials. No statistically significant effect of histopathologic regression in the LNs on long-term survival was seen.


2021 ◽  
Author(s):  
Mahshid Kashkoulibehroozi ◽  
Shirin Tahereh Haghighi ◽  
Zhale Mohsenifar

UNSTRUCTURED Background: Rectal tumors are important malignancies and prediction of prognosis after neoadjuvant therapy is important to improve the prognosis process. The purpose of this study was to determine therole ofneoadjuvant therapy in lymph node regression and primary rectal tumor as well as its association with prognosis. Methods and materials: In this descriptive study, 40 consecutive patients with rectal tumor who were referred toTaleghani Hospital for surgery from 2011 to 2018 were enrolled. Moreover, theneoadjuvant therapy role in lymph node regression and primary rectal tumor was determined as well as its association with prognosis. Results: The results of this study demonstrate that there was no tumor regression in 20% of patients and it wasalso less than 25%, 25-50%, 50-75%, and complete in 22.5%, 35%, 20%, and 2.5% of the patients,respectively. The lymph node regression was complete in 5% of the patients and it wasalso less than 25% in 20% and more than 25% in 50% of them. In addition, it was with no regression in 25% of the patients. The lymph node regression was related to N stage (P=0.018), primary tumor regression grade (P=0.001), yPT (P=0.008), and yPN (P=0.020); however, it was not related to prognosis (P > 0.05). Conclusions: Totally, according to the obtained results, it can be concluded thatneoadjuvant therapy plays a good role in lymph node regression and primary rectal tumor, but it has no association with prognosis. Keywords:Neoadjuvant therapy, Lymph node regression, Primary rectal tumor, Prognosis


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