Pretherapy nuclear factor-κB status, chemoradiation resistance, and metastatic progression in esophageal carcinoma

Izzo, Julie; Correa, Arlene M.; Wu, Tsung Teh; Malhotra, Usha; Chao, C.; Luthra, Rajyalakshmi; Ensor, Joe; Dekovich, Alexander A.; Liao, Zhongxing; Hittelman, Walter N.; Aggarwal, Bharat B.; Ajani, Jaffer A.

doi:10.1158/1535-7163.mct-06-0351

Cited by 61 publications

(63 citation statements)

References 25 publications

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“…We also showed that in patients who are undergoing preoperative chemoradiation, nuclear NF-nB was independently associated with poor disease-free survival (DFS) or overall survival (OS; refs. 28,29). In our studies, we observed two distinct NF-nB patterns whereas some E/GEJ cancers presented intrinsic (i.e., pretreatment) NF-nB activation, whereas in others the activation seemed to follow the exposure to chemoradiation treatment.…”

Section: Introductionsupporting

confidence: 46%

Clinical Biology of Esophageal Adenocarcinoma after Surgery Is Influenced by Nuclear Factor-κB Expression

Izzo

Malhotra²,

Wu³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: The expression of transcriptional factor nuclear factor KB (NF-KB) in untreated esophageal cancer specimens from patients who receive preoperative chemoradiation is associated with aggressive clinical biology. We hypothesized that nuclear NF-KB would define clinical biology even when surgery is used as primary therapy. Methods: Consecutive patients who did not receive any preoperative therapy were selected. Surgical cancer specimens were examined for nuclear NF-KB and correlated with overall survival (OS) and disease-free survival (DFS). Results: One hundred twenty-three patients (stage I, 9%; stage II, 24%; stage III, 53%; stage IV, 15%) with adenocarcinoma who underwent surgery as primary therapy were analyzed. Most patients were men (90%) and the median age was 63 years. For all 123 patients, the median DFS was 21 months and the median OS was 28 months. Nuclear NF-KB

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Section: Introductionsupporting

confidence: 46%

Clinical Biology of Esophageal Adenocarcinoma after Surgery Is Influenced by Nuclear Factor-κB Expression

Izzo

Malhotra²,

Wu³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…However, nonsteroidal antiinflammatory drugs are not specific and usually have side effects that prevent their long-term administration. Advances in preclinical research have highlighted the fact that resistance to chemotherapy as well as radiotherapy are caused by the chronic activation of NF-B (24 ). Several inhibitors of NF-B or STAT3 have been reported to enhance the effect of therapeutic agents in the treatment of bone metastasis in prostate cancer.…”

Section: Tumor Microenvironment and Cancer Therapymentioning

confidence: 99%

Targeting the Tumor Microenvironment for Cancer Therapy

2013

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BACKGROUND With the emergence of the tumor microenvironment as an essential ingredient of cancer malignancy, therapies targeting the host compartment of tumors have begun to be designed and applied in the clinic. CONTENT The malignant features of cancer cells cannot be manifested without an important interplay between cancer cells and their local environment. The tumor infiltrate composed of immune cells, angiogenic vascular cells, lymphatic endothelial cells, and cancer-associated fibroblastic cells contributes actively to cancer progression. The ability to change these surroundings is an important property by which tumor cells are able to acquire some of the hallmark functions necessary for tumor growth and metastatic dissemination. Thus in the clinical setting the targeting of the tumor microenvironment to encapsulate or destroy cancer cells in their local environment has become mandatory. The variety of stromal cells, the complexity of the molecular components of the tumor stroma, and the similarity with normal tissue present huge challenges for therapies targeting the tumor microenvironment. These issues and their interplay are addressed in this review. After a decade of intensive clinical trials targeting cellular components of the tumor microenvironment, more recent investigations have shed light on the important role in cancer progression played by the noncellular stromal compartment composed of the extracellular matrix. SUMMARY A better understanding of how the tumor environment affects cancer progression should provide new targets for the isolation and destruction of cancer cells via interference with the complex crosstalk established between cancer cells, host cells, and their surrounding extracellular matrix.

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“…Using the Spitzer index, there was no difference in global quality of life however, a significantly greater decrease in quality of life was observed in the surgery arm during the postoperative period (7.52 vs. 8.45, p<0.01, respectively) [65]. A separate analysis revealed that compared with split course radiation, patients who received standard course radiation had improved 2-year local relapse free survival rates (77% vs. 57%, p=0.002) but no significant difference in overall survival (37% vs. 31%) [66].…”

Section: Is Surgery Necessary Following Chemoradiation?mentioning

confidence: 90%

Advances in the management of esophageal cancer

Minsky

2015

Marmara Medical Journal

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The management of clinical stage III and IVa esophageal cancer has evolved in the past 2 decades. Based on the Cross trial, neoadjuvant chemoradiation, followed by surgical resection has become standard. For medically inoperable, definitive chemoradiation is most commonly used. The standard radiation dose is 50.4 Gy although trials of doseescalation are ongoing. At the current time, there are no definitive biomarkers to predict response. Keywords:Esophageal cancer, Radiation therapy, Chemotherapy, Dose-escalation NONOPERATIVE THERAPY Radiation therapy aloneRadiation therapy alone is limited to palliation or for patients who are medically unable to tolerate chemotherapy. The 5-year survival rate for patients treated with conventional doses of radiation therapy alone is 0-10% [1-3]. In the radiation therapy alone arm of the RTOG 85-01 trial in which patients received 64 Gy at 2 Gy/day with conventional techniques, all patients were all dead of disease by 3 years [4,5] Dose intensification with brachytherapyBrachytherapy can be delivered by low or high dose rates and has previously been used as a boost following external beam radiation therapy or chemoradiation [7][8][9][10][11][12][13][14][15][16]. This technique is limited by the effective treatment distance. The primary isotope is 192Ir, which is usually prescribed to treat to a distance of 1 cm from the source. Therefore, as confirmed by pathologic analysis of treated specimens, any portion of the tumor which is >1 cm from the source will receive a suboptimal radiation dose [17].Retrospective and single institution trials suggest that there is no advantage of adding brachytherapy to external beam radiation. Chemoradiation plus brachytherapy was tested prospectively by the RTOG 92-07 trial. A total of 75 patients with cancers of the thoracic esophagus (92% squamous cell, 8% adenocarcinoma) received the RTOG 85-01 50 Gy chemoradiation regimen followed by a boost during cycle 3 of chemotherapy with either low dose rate or high dose rate intraluminal brachytherapy [22]. Due to low accrual the low dose rate option was discontinued and the analysis was limited to patients who received the high dose rate treatment. High dose rate brachytherapy was delivered in weekly fractions of 5 Gy during weeks 8, 9, and 10. Several patients developed fistulas and the fraction delivered at week 10 was discontinued. The complete response rate was 73%. With a median follow-up of only 11 months, local failure as the first site of failure was 27%. Acute toxicities were high. These included 58% grade 3, 26% grade 4, and 8% grade 5 (treatment-related death). The

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Pretherapy nuclear factor-κB status, chemoradiation resistance, and metastatic progression in esophageal carcinoma

Cited by 61 publications

References 25 publications

Clinical Biology of Esophageal Adenocarcinoma after Surgery Is Influenced by Nuclear Factor-κB Expression

Clinical Biology of Esophageal Adenocarcinoma after Surgery Is Influenced by Nuclear Factor-κB Expression

Targeting the Tumor Microenvironment for Cancer Therapy

Advances in the management of esophageal cancer

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