scholarly journals Combined Therapy of Locally Advanced Oesophageal and Gastro–Oesophageal Junction Adenocarcinomas: State of the Art and Aspects of Predictive Factors

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4591
Author(s):  
Milan Vošmik ◽  
Jindřich Kopecký ◽  
Stanislav John ◽  
Ondřej Kubeček ◽  
Petr Lochman ◽  
...  
Keyword(s):  
Predictive Factors ◽  
Combined Therapy ◽  
Treatment Options ◽  
Locally Advanced ◽  
Predictive Biomarkers ◽  
Preoperative Chemoradiotherapy ◽  
Current Treatment ◽  
Her2 Status ◽  
Perioperative Chemotherapy ◽  
Optimal Treatment Strategy

The following main treatment approaches are currently used in locally advanced adenocarcinomas of the oesophagus and gastrooesophageal junction (GOJ): preoperative chemoradiotherapy and surgery, and perioperative chemotherapy and surgery. While preoperative chemoradiotherapy is used primarily in oesophageal tumours, perioperative chemotherapy is the treatment of choice in Western countries for gastric cancer. The optimal treatment strategy for GOJ adenocarcinoma is still not clear. In comparison to other malignancies, biomarkers are used as predictive factors in distal oesophageal and GOJ adenocarcinomas in a very limited way, and moreover, only in metastatic stages (e.g., HER2 status, or microsatellite instability status). The aim of the article is to provide an overview of current treatment options in locally advanced adenocarcinomas of oesophagus and GOJ based on the latest evidence, including the possible potential of predictive biomarkers in optimizing treatment.

Is There a Precise Adjuvant Therapy for Esophagogastric Carcinoma?

2018 ◽  
pp. 280-291 ◽  
Author(s):  
Elizabeth Cartwright ◽  
Florence K. Keane ◽  
Peter C. Enzinger ◽  
Theodore Hong ◽  
Ian Chau
Keyword(s):  
Clinical Trials ◽  
Treatment Options ◽  
Locally Advanced ◽  
Predictive Biomarkers ◽  
Standard Of Care ◽  
Global Consensus ◽  
Esophagogastric Cancer ◽  
Genetic Features ◽  
Related Mortality ◽  
Optimal Treatment Strategy

Esophagogastric cancer remains a leading cause of cancer-related mortality worldwide. The prognosis for patients with locally advanced disease is poor and the majority of patients with operable tumors treated with surgery alone will have recurrent disease. A multimodal approach to treatment with adjunctive chemotherapy or chemoradiotherapy is therefore the standard of care for these patients. However, there is no global consensus on the optimal treatment strategy and international guidelines vary. National clinical trials inform local practice: neoadjuvant, perioperative, and adjuvant chemotherapy and radiotherapy combinations are all possible treatment options in the management of resectable esophagogastric cancer. A number of clinical trials are ongoing, which seek to directly compare multimodal treatment options and hope to provide clarity in this area. Furthermore, increased understanding of the molecular and genetic features of esophagogastric cancer may help to guide management of operable disease by determining optimal patient selection through identification of predictive biomarkers of response and the application of novel targeted agents.

Unanswered Questions in the Management of Gastroesophageal Junction Adenocarcinoma: An Overview from the Medical Oncologist's Perspective

2013 ◽  
pp. e155-e159
Author(s):  
Manish A. Shah
Keyword(s):  
Gastric Cancer ◽  
Treatment Options ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Preoperative Chemoradiotherapy ◽  
Phase Iii ◽  
Perioperative Chemotherapy ◽  
Two Phase ◽  
Multiple Treatment ◽  
Gastroesophageal Junction Adenocarcinoma

Patients with gastroesophageal junction (GEJ) adenocarcinoma have multiple treatment options; however, are victims of lack of consensus and wide variation in treatment, sometimes within the same hospital. While there is a consensus that surgery alone is inadequate for locally advanced disease, locoregional treatment has become the point for debate. Only in 2010 was the reclassification of GEJ cancers as esophageal cancers. Treatment options remain as varied as the classification of GEJ cancers: preoperative chemoradiotherapy, definitive chemoradiation, perioperative chemotherapy, and resection followed by postoperative chemoradiation. Several studies have examined the varying treatment paradigms; however, many fall short due to methodology or sample size. The MAGIC study determined perioperative chemotherapy to be an acceptable standard treatment option for patients with gastric cancer, althouth a significant portion of enrolled patients had distal esophageal and GEJ adenocarcinoma. The CROSS study concluded combination chemotherapy and radiation before resection beneficial. Preoperative therapy in cases of GEJ is beneficial for survival, but not as much impact is seen as in esophageal SCC, which exhibits an increased sensitivity to CRT. There is concurrence with two phase III studies from Japan and Korea on the role of adjuvant chemotherapy for gastric cancer. However, the applicability of these studies to GEJ adenocarcinoma remains a question, especially with the significantly different epidemiology of increased proximal and GEJ tumors in the West compared to Asia. To move forward with this increasingly prevalent disease, we will need to do more than understand the multiple treatment paradigms—we will need to select a strategy and examine it.

scholarly journals PERIOPERATIVE CHEMOTHERAPY IN LOCALLY ADVANCED GASTRIC CANCER

2013 ◽  
Vol 50 (3) ◽  
pp. 236-242 ◽  
Author(s):  
Thales Paulo BATISTA ◽  
Candice Amorim de Araujo Lima SANTOS ◽  
Gustavo Fernandes Godoy ALMEIDA
Keyword(s):  
Gastric Cancer ◽  
Therapeutic Strategy ◽  
Multimodal Therapy ◽  
Standard Treatment ◽  
Treatment Options ◽  
Locally Advanced ◽  
Special Focus ◽  
Perioperative Chemotherapy ◽  
Locally Advanced Gastric Cancer ◽  
Advanced Stages

Gastric cancer is one of the most common cancers and a main cause of cancer-related death worldwide, since the majority of patients suffering of this malignancy are usually faced with a poor prognosis due to diagnosis at later stages. In order to improve treatment outcomes, the association of surgery with chemo and/or radiotherapy (multimodal therapy) has become the standard treatment for locally advanced stages. However, despite several treatment options currently available for management of these tumors, perioperative chemotherapy has been mainly accepted for the comprehensive therapeutic strategy including an appropriated D2-gastrectomy. This manuscript presents a (nonsystematic) critical review about the use of perioperative chemotherapy, with a special focus on the drugs delivery.

scholarly journals MiR-144 overexpression as a promising therapeutic strategy to overcome glioblastoma cell invasiveness and resistance to chemotherapy

2019 ◽  
Vol 28 (16) ◽  
pp. 2738-2751 ◽  
Author(s):  
Ana M S Cardoso ◽  
Madalena Sousa ◽  
Catarina M Morais ◽  
Liliana R Oancea-Castillo ◽  
Anne Régnier-Vigouroux ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Cell Metabolism ◽  
Combined Therapy ◽  
Treatment Options ◽  
Primary Brain Tumor ◽  
Current Treatment ◽  
Cancer Therapies ◽  
Current Standard ◽  
Aberrant Expression ◽  
Post Surgery

Abstract Glioblastoma (GB) is the most aggressive and common form of primary brain tumor, characterized by fast proliferation, high invasion, and resistance to current standard treatment. The average survival rate post-diagnosis is only of 14.6 months, despite the aggressive standard post-surgery treatment approaches of radiotherapy concomitant with chemotherapy with temozolomide. Altered cell metabolism has been identified as an emerging cancer hallmark, including in GB, thus offering a new target for cancer therapies. On the other hand, abnormal expression levels of miRNAs, key regulators of multiple molecular pathways, have been correlated with pathological manifestations of cancer, such as chemoresistance, proliferation, and resistance to apoptosis. In this work, we hypothesized that gene therapy based on modulation of a miRNA with aberrant expression in GB and predicted to target crucial metabolic enzymes might impair tumor cell metabolism. We found that the increase of miR-144 levels, shown to be downregulated in U87 and DBTRG human GB cell lines, as well as in GB tumor samples, promoted the downregulation of mRNA of enzymes involved in bioenergetic pathways, with consequent alterations in cell metabolism, impairment of migratory capacity, and sensitization of DBTRG cells to a chemotherapeutic drug, the dichloroacetate (DCA). Taken together, our findings provide evidence that the miR-144 plus DCA combined therapy holds promise to overcome GB-acquired chemoresistance, therefore deserving to be explored toward its potential application as a complementary therapeutic approach to the current treatment options for this type of brain tumor.

scholarly journals Advances in systemic therapy for advanced pancreatobiliary malignancies

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 105
Author(s):  
Thorvardur R Halfdanarson ◽  
Sigurdis Haraldsdottir ◽  
Mitesh J Borad
Keyword(s):  
Radiation Therapy ◽  
Systemic Therapy ◽  
Patient Survival ◽  
Advanced Disease ◽  
Treatment Options ◽  
Locally Advanced ◽  
Current Treatment ◽  
Targeted Treatments ◽  
Poor Treatment ◽  
Novel Approaches

Pancreatobiliary malignancies are relatively uncommon and the overall prognosis is poor. Treatment options for advanced disease are limited to systemic therapy for metastatic disease and a combination of systemic therapy and radiation therapy for locally advanced but unresectable tumors. There have been significant advances in the treatment of pancreatobiliary cancers in recent years but the prognosis for patient survival remains disappointingly poor. We review the current treatment options for locally advanced pancreatobiliary malignancies and highlight recent advances in systemic therapy, including novel approaches using targeted treatments.

Perioperative chemotherapy alone versus preoperative chemoradiotherapy for locally advanced distal esophageal and gastroesophageal junction cancer: A 10-year review of the British Columbia (BC) Cancer Registry.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4028-4028
Author(s):  
Shiru Lucy Liu ◽  
Irene S. Yu ◽  
Sally CM Lau ◽  
Yizhou Zhao ◽  
Devin Schellenberg ◽  
...  
Keyword(s):  
Cancer Registry ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Preoperative Chemoradiotherapy ◽  
Pathologic Response ◽  
R0 Resection ◽  
Perioperative Chemotherapy ◽  
Cancer Specific Survival ◽  
Significant Difference

4028 Background: The optimal treatment strategy for resectable cancer of the distal esophagus (ESOPH) and gastroesophageal junction (GEJ) remains controversial. This study evaluates patterns of practice in BC, rates of complete surgical resection, and survival outcomes of patients treated with perioperative chemotherapy alone (CA), per MAGIC or FLOT4 protocol, versus preoperative chemoradiotherapy (CRT), per CROSS protocol. Methods: We undertook a provincial analysis of initially resectable, locally advanced, cancer of the ESOPH and/or GEJ who underwent surgery in BC, from 2008 to 2018. Baseline patient, tumor, treatment, and clinical outcome data were collected from the BC Cancer Registry. Kaplan-Meier survival and multivariate regression analyses were conducted. Results: Among 575 patients, 468 underwent surgery and were included (Table). More surgeries were aborted intraoperatively in the CA cohort compared to CRT (12% vs 2%, p<0.001). There was no difference in age, sex, or ECOG performance status among the cohorts, and 83% were adenocarcinoma. While 82% of ESOPH involving GEJ (N = 251, 54%) is treated with CRT, only 53% of GEJ alone (N=217, 46%) is treated with CRT (p<0.001). CRT is associated with a higher rate of complete or partial pathologic response compared to CA (59% vs 39%, p=0.002). R0 resection rate was 90% and 94% in the CA and CRT cohort, respectively (p=0.383). There is no statistically significant difference in overall survival, with medians of 29.6 and 26.0 months for patients treated with CA and CRT, respectively (p=0.723). Cancer-specific survival is also not significantly different (p=0.565). In the CA cohort, 37% of patients complete all 8 cycles of FLOT and 52% of patients complete all 6 cycles of MAGIC (p=0.396). Conclusions: Patients treated with CRT have higher rates of complete resection and pathologic response, but their survival is not significantly different compared to those treated with CA. [Table: see text]

Prognostic immune markers for recurrence and survival in locally advanced esophageal adenocarcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 50-50
Author(s):  
Laila Babar ◽  
Ali Hussainy Zaidi ◽  
Ashten N. Omstead ◽  
Ping Zheng ◽  
Ronan Joseph Kelly ◽  
...  
Keyword(s):  
Cox Model ◽  
Treatment Options ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Predictive Biomarkers ◽  
Tumor Stage ◽  
Classification Performance ◽  
Ratio Test ◽  
Novel Treatments ◽  
Best Fit

50 Background: Treatment options and risk stratification for esophageal adenocarcinomas (EAC) primarily rely on clinical and pathological criteria, such as tumor stage and pathological response (PR) evaluation. However, with immunotherapy showing hints of activity in EAC there is an emerging need to develop new predictive biomarkers that will not only identify high-risk patients but also unlock novel therapeutic strategies. The aim of this study was to evaluate if LAG3, TIM3, IDO and CXCL9 gene expression along with pathological classifiers correlate with recurrence and/or death in EAC. Methods: Clinical and histopathology data on 49 resectable EAC patients was captured. Mean age at diagnosis was 64.2 years with a median follow up of 21.2 months. Laser capture microdissection followed by qRT-PCR was performed on pretreatment FFPE samples to quantify LAG3, TIM3, IDO and CXCL9 gene levels. Statistical tools established individual biomarker cutoffs and these were correlated with clinical outcomes. Results: For disease free survival, a best fit Cox model was generated consisting of PR (HR=9.54, 95% CI = 2.13 ~ 42.62, p = .003), LAG3 (HR = 2.86, 95% CI = 1.03 ~ 7.94, p = .044), and CXCL9 (HR = 0.40, 95% CI = 0.16 ~ 0.99, p = .049). Moreover, the classification performance of the 3 predictor Cox model was deemed superior to PR alone; P = 0.0001 (Likelihood Ratio Test (LRT)) indicated strong significance in predictability with the recurrence model. For overall survival, a best fit Cox model was generated consisting of TIM3 (HR = 4.43, 95% CI= 1.70 ~ 11.5, p = .002) PR (HR = 3.09, 95% CI= 1.00 ~ 9.56, p = .051) and IDO (HR = 0.31, 95% CI = 0.11 ~ 0.82, p = .019). Likewise, the classification performance of the 3 predictor Cox model was deemed superior to PR alone; P = 0.0004 (LRT) indicated strong significance in predictability with the survival model. Conclusions: LAG3, TIM3, IDO and CXCL9 expression in conjunction with PR to neoadjuvant therapy provide superior tools to predict recurrence and death in locally advanced EAC patients. Additionally, given the paucity of treatment options for esophageal cancer we must check for these markers early on in the disease course to better risk stratify patients and provide newer targets for novel treatments.

scholarly journals Current treatment options for locally advanced prostate cancer: EAU (-SIOG) guidelines view and recommendations

2020 ◽  
Vol 19 ◽  
pp. e1804-e1805
Author(s):  
L. Moris ◽  
M.C. Cumberbatch ◽  
T. Van Den Broeck ◽  
G. Gandaglia ◽  
N. Fossati ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Treatment Options ◽  
Locally Advanced ◽  
Current Treatment ◽  
Locally Advanced Prostate Cancer
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