scholarly journals Towards Personalization in the Curative Treatment of Gastric Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Astrid E. Slagter ◽  
Marieke A. Vollebergh ◽  
Edwin P. M. Jansen ◽  
Johanna W. van Sandick ◽  
Annemieke Cats ◽  
...  

Gastric cancer is the fifth most common cancer worldwide and has a high mortality rate. In the last decades, treatment strategy has shifted from an exclusive surgical approach to a multidisciplinary strategy. Treatment options for patients with resectable gastric cancer as recommended by different worldwide guidelines, include perioperative chemotherapy, pre- or postoperative chemoradiotherapy and postoperative chemotherapy. Although gastric cancer is a heterogeneous disease with respect to patient-, tumor-, and molecular characteristics, the current standard of care is still according to a one-size-fits-all approach. In this review, we discuss the background of the different treatment strategies in resectable gastric cancer including the current standard, the specific role of radiotherapy, and describe the current areas of research and potential strategies for personalization of therapy.

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 80 ◽  
Author(s):  
Tom van den Ende ◽  
Emil ter Veer ◽  
Mélanie Machiels ◽  
Rosa Mali ◽  
Frank Abe Nijenhuis ◽  
...  

Background: Alternatives in treatment-strategies exist for resectable gastric cancer. Our aims were: (1) to assess the benefit of perioperative, neoadjuvant and adjuvant treatment-strategies and (2) to determine the optimal adjuvant regimen for gastric cancer treated with curative intent. Methods: PubMed, EMBASE, CENTRAL, and ASCO/ESMO conferences were searched up to August 2017 for randomized-controlled-trials on the curative treatment of resectable gastric cancer. We performed two network-meta-analyses (NMA). NMA-1 compared perioperative, neoadjuvant and adjuvant strategies only if there was a direct comparison. NMA-2 compared different adjuvant chemo(radio)therapy regimens, after curative resection. Overall-survival (OS) and disease-free-survival (DFS) were analyzed using random-effects NMA on the hazard ratio (HR)-scale and calculated as combined HRs and 95% credible intervals (95% CrIs). Results: NMA-1 consisted of 9 direct comparisons between strategies for OS (14 studies, n = 4187 patients). NMA-2 consisted of 16 direct comparisons between adjuvant chemotherapy/chemoradiotherapy regimens for OS (37 studies, n = 10,761) and 14 for DFS (30 studies, n = 9714 patients). Compared to taxane-based-perioperative-chemotherapy, surgery-alone (HR = 0.58, 95% CrI = 0.38–0.91) and perioperative-chemotherapy regimens without a taxane (HR = 0.79, 95% CrI = 0.58–1.15) were inferior in OS. After curative-resection, the doublet oxaliplatin-fluoropyrimidine (for one-year) was the most efficacious adjuvant regimen in OS (HR = 0.47, 95% CrI = 0.28–0.80). Conclusions: For resectable gastric cancer, (1) taxane-based perioperative-chemotherapy was the most promising treatment strategy; and (2) adjuvant oxaliplatin-fluoropyrimidine was the most promising regimen after curative resection. More research is warranted to confirm or reproach these findings.


2010 ◽  
Vol 8 (4) ◽  
pp. 417-425 ◽  
Author(s):  
Prajnan Das ◽  
Yixing Jiang ◽  
Jeffrey H. Lee ◽  
Manoop S. Bhutani ◽  
William A. Ross ◽  
...  

Most patients with localized gastric cancer require multimodality therapy. Surgery is the primary treatment for localized gastric cancer, although controversy exists about the optimal extent of lymphadenectomy in these patients. Recent studies have evaluated the role of laparoscopic surgery and endoscopic mucosal resection in selected patients. Multimodality treatment options for these patients include post-operative chemoradiation and perioperative chemotherapy. The Intergroup 0116 trial demonstrated that patients treated with surgery and post-operative chemoradiation had significantly higher overall survival compared to patients treated with surgery alone. The MAGIC trial showed that patients treated with perioperative epirubicin, cisplatin, and 5-fluorouracil had significantly higher overall survival compared to patients treated with surgery alone. Other recent trials have evaluated the roles of preoperative chemoradiation and adjuvant chemotherapy. Multidisciplinary evaluation plays a crucial role in the management of these patients.


Author(s):  
Yoon-Koo Kang ◽  
Changhoon Yoo

Overview: After much debate, adjuvant therapy has become the standard of care worldwide for resected localized gastric cancer. However, geographic differences exist in standard adjuvant treatments: postoperative chemoradiation in North America, perioperative chemotherapy in the United Kingdom, and postoperative chemotherapy in East Asia. Now that D2 gastrectomy has been recognized as the optimal surgery for localized gastric cancer in the West as well as in Asia, the standard adjuvant treatments used in the West may need to be reconsidered. One of the most important issues in adjuvant therapy for localized gastric cancer is how to improve the clinical outcomes of current standard treatments. Recent Cancer and Leukemia Group B (CALGB) and AMC studies suggest that simply intensifying chemotherapy by adding more agents or prolonging treatment duration is insufficient. However, new strategies like early initiation of chemotherapy and/or intraperitoneal chemotherapy may further improve the current standard adjuvant therapy. In the era of targeted therapy, the role of biologic agents for gastric cancer should also be explored in the adjuvant setting. With a deeper understanding of the molecular biology of gastric cancer, adjuvant therapy for patients with localized gastric cancer can be optimized and individualized.


2018 ◽  
Vol 154 (6) ◽  
pp. S-1258
Author(s):  
Brooke Vuong ◽  
Ahmed Dehal ◽  
Amanda Graff-Baker ◽  
Trevan Fischer ◽  
Shrawan G. Gaitonde ◽  
...  

2021 ◽  
Vol 10 (15) ◽  
pp. 3372
Author(s):  
Tsuyoshi Takeda ◽  
Takashi Sasaki ◽  
Takeshi Okamoto ◽  
Naoki Sasahira

Periampullary cancers are often diagnosed at advanced stages and can cause both biliary and duodenal obstruction. As these two obstructions reduce patients’ performance status and quality of life, appropriate management of the disease is important. Combined malignant biliary and duodenal obstruction is classified according to the location and timing of the duodenal obstruction, which also affect treatment options. Traditionally, surgical bypass (gastrojejunostomy and hepaticojejunostomy) has been performed for the treatment of unresectable periampullary cancer. However, it has recently been substituted by less invasive endoscopic procedures due to its high morbidity and mortality. Thus, endoscopic double stenting (transpapillary stenting and enteral stenting) has become the current standard of care. Limitations of transpapillary stenting include its technical difficulty and the risk of duodenal-biliary reflux. Recently, endoscopic ultrasound-guided procedures have emerged as a novel platform and have been increasingly utilized in the management of biliary and duodenal obstruction. As the prognosis of periampullary cancer has improved due to recent advances in chemotherapy, treatment strategies for biliary and duodenal obstruction are becoming more important. In this article, we review the treatment strategies for combined malignant biliary and duodenal obstruction based on the latest evidence.


Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1304
Author(s):  
Evangelos Koustas ◽  
Eleni-Myrto Trifylli ◽  
Panagiotis Sarantis ◽  
Nikolaos I. Kontolatis ◽  
Christos Damaskos ◽  
...  

Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. The three entirely variable entities have distinct epidemiology, molecular characteristics, prognosis, and strategies for clinical management. However, many gastric tumors appear to be resistant to current chemotherapeutic agents. Moreover, a significant number of gastric cancer patients, with a lack of optimal treatment strategies, have reduced survival. In recent years, multiple research data have highlighted the importance of autophagy, an essential catabolic process of cytoplasmic component digestion, in cancer. The role of autophagy as a tumor suppressor or tumor promoter mechanism remains controversial. The multistep nature of the autophagy process offers a wide array of targetable points for designing novel chemotherapeutic strategies. The purpose of this review is to summarize the current knowledge regarding the interplay between gastric cancer development and the autophagy process and decipher the role of autophagy in this kind of cancer. A plethora of different agents that direct or indirect target autophagy may be a novel therapeutic approach for gastric cancer patients.


2020 ◽  
Vol 15 (7) ◽  
pp. 607-613 ◽  
Author(s):  
Haiping Liu ◽  
Yiqian Liu ◽  
Xiaochuan Zhang ◽  
Xiaodong Wang

Gastric cancer (GC) is the fourth-most common cancer in the world, with an estimated 1.034 million new cases in 2015, and the third-highest cause of cancer deaths, estimated at 785,558, in 2014. Early diagnosis and treatment greatly affect the survival rate in patients with GC: the 5‐year survival rate of early GC reaches 90%‐95%, while the mortality rate significantly increases if GC develops to the late stage. Recently, studies for the role of RhoA in the diseases have become a hot topic, especially in the development of tumors. A study found that RhoA can regulate actin polymerization, cell adhesion, motor-myosin, cell transformation, and the ability to participate in the activities of cell movement, proliferation, migration, which are closely related to the invasion and metastasis of tumor cells. However, the specific role of RhoA in tumor cells remains to be studied. Therefore, our current study aimed to briefly review the role of RhoA in GC, especially for its associated signaling pathways involved in the GC progression.


2021 ◽  
Vol 22 (2) ◽  
pp. 587
Author(s):  
Alexandru Oprita ◽  
Stefania-Carina Baloi ◽  
Georgiana-Adeline Staicu ◽  
Oana Alexandru ◽  
Daniela Elise Tache ◽  
...  

Nowadays, due to recent advances in molecular biology, the pathogenesis of glioblastoma is better understood. For the newly diagnosed, the current standard of care is represented by resection followed by radiotherapy and temozolomide administration, but because median overall survival remains poor, new diagnosis and treatment strategies are needed. Due to the quick progression, even with aggressive multimodal treatment, glioblastoma remains almost incurable. It is known that epidermal growth factor receptor (EGFR) amplification is a characteristic of the classical subtype of glioma. However, targeted therapies against this type of receptor have not yet shown a clear clinical benefit. Many factors contribute to resistance, such as ineffective blood–brain barrier penetration, heterogeneity, mutations, as well as compensatory signaling pathways. A better understanding of the EGFR signaling network, and its interrelations with other pathways, are essential to clarify the mechanisms of resistance and create better therapeutic agents.


2021 ◽  
Vol 14 ◽  
pp. 175628482110244
Author(s):  
Vanessa Wookey ◽  
Axel Grothey

Colorectal cancer (CRC) is the third most common cancer type in both men and women in the USA. Most patients with CRC are diagnosed as local or regional disease. However, the survival rate for those diagnosed with metastatic disease remains disappointing, despite multiple treatment options. Cancer therapies for patients with unresectable or metastatic CRC are increasingly being driven by particular biomarkers. The development of various immune checkpoint inhibitors has revolutionized cancer therapy over the last decade by harnessing the immune system in the treatment of cancer, and the role of immunotherapy continues to expand and evolve. Pembrolizumab is an anti-programmed cell death protein 1 immune checkpoint inhibitor and has become an essential part of the standard of care in the treatment regimens for multiple cancer types. This paper reviews the increasing evidence supporting and defining the role of pembrolizumab in the treatment of patients with unresectable or metastatic CRC.


2021 ◽  
Vol 14 (1) ◽  
pp. 51
Author(s):  
Brinda Balasubramanian ◽  
Simran Venkatraman ◽  
Kyaw Zwar Myint ◽  
Tavan Janvilisri ◽  
Kanokpan Wongprasert ◽  
...  

Cholangiocarcinoma (CCA), a group of malignancies that originate from the biliary tract, is associated with a high mortality rate and a concerning increase in worldwide incidence. In Thailand, where the incidence of CCA is the highest, the socioeconomic burden is severe. Yet, treatment options are limited, with surgical resection being the only form of treatment with curative intent. The current standard-of-care remains adjuvant and palliative chemotherapy which is ineffective in most patients. The overall survival rate is dismal, even after surgical resection and the tumor heterogeneity further complicates treatment. Together, this makes CCA a significant burden in Southeast Asia. For effective management of CCA, treatment must be tailored to each patient, individually, for which an assortment of targeted therapies must be available. Despite the increasing numbers of clinical studies in CCA, targeted therapy drugs rarely get approved for clinical use. In this review, we discuss the shortcomings of the conventional clinical trial process and propose the implementation of a novel concept, co-clinical trials to expedite drug development for CCA patients. In co-clinical trials, the preclinical studies and clinical trials are conducted simultaneously, thus enabling real-time data integration to accurately stratify and customize treatment for patients, individually. Hence, co-clinical trials are expected to improve the outcomes of clinical trials and consequently, encourage the approval of targeted therapy drugs. The increased availability of targeted therapy drugs for treatment is expected to facilitate the application of precision medicine in CCA.


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