Preoperative chemotherapy for resectable thoracic esophageal cancer

Kidane, Biniam; Coughlin, Shaun; Vogt, Kelly; Malthaner, Richard

doi:10.1002/14651858.cd001556.pub3

Cited by 92 publications

(52 citation statements)

References 42 publications

(6 reference statements)

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“…[4] A recently published comprehensive metaanalysis found that neoadjuvant chemotherapy improved the likelihood of complete (R0) resection and was associated with improved overall survival compared to surgical resection alone with a 12% decrease in the mortality hazard. [4] In parallel, studies evaluating neoadjuvant chemoradiation therapy have demonstrated high rates of R0 resection and improved survival as well.…”

Section: Introductionmentioning

confidence: 99%

Neoadjuvant Chemotherapy versus Chemoradiation Prior to Esophagectomy: Impact on Rate of Complete Pathologic Response and Survival in Esophageal Cancer Patients

Samson

Robinson

Bradley

et al. 2016

Journal of Thoracic Oncology

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Purpose To evaluate differences in pathologic complete response (pCR) rates and overall survival among patients receiving either neoadjuvant chemotherapy or chemoradiation prior to esophagectomy for locally advanced esophageal cancer. Patients and methods Esophageal cancer patients receiving either neoadjuvant chemotherapy or chemoradiation prior to esophagectomy were identified using the National Cancer Data Base (NCDB). Univariate analysis compared patient, tumor, and postoperative outcome characteristics. Logistic regression was performed to identify variables associated with achieving pCR. Kaplan-Meier analysis was performed to compare overall median survival by neoadjuvant therapy type and pCR status. Finally, a Cox proportional hazards model was fitted to identify variables associated with increased mortality hazard. Results From 2006 – 2012, 916/7,338 (12.5%) of patients received neoadjuvant chemotherapy while 6,422 (87.5%) received neoadjuvant chemoradiation. Neoadjuvant chemoradiation patients were more likely to achieve pCR (17.2% versus 6.4%, p<0.001) and less likely to have positive margins (5.6% versus 11.5%, p<0.001) than neoadjuvant chemotherapy patients, with no difference in 30- or 90-day mortality. Achieving pCR was associated with improved overall median survival (59.5 months ± 4.0 versus 30.1 months ± 0.76 for those with persistent disease, p<0.001). On logistic regression, neoadjuvant chemoradiation therapy was independently associated with achieving pCR (Odds Ratio 2.75, 2.01 – 3.77, p<0.001). Despite improvement in pCR rate with neoadjuvant chemoradiation, neoadjuvant therapy type was not independently associated with long-term survival (HR 1.12, 95% CI 0.97 – 1.30, p=0.12). Conclusion While neoadjuvant chemoradiation is more successful in downstaging esophageal cancer prior to esophagectomy, this therapy was not independently prognostic for improved long-term survival. Other factors affecting long-term survival among pathologic complete responders and among patients with persistent disease should be investigated to clarify this association.

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Section: Introductionmentioning

confidence: 99%

Neoadjuvant Chemotherapy versus Chemoradiation Prior to Esophagectomy: Impact on Rate of Complete Pathologic Response and Survival in Esophageal Cancer Patients

Samson

Robinson

Bradley

et al. 2016

Journal of Thoracic Oncology

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“…[2,3] For operable patients with clinical evidence of nodal disease, induction therapy (either chemotherapy or chemoradiation therapy) is an acceptable treatment option prior to esophagectomy. [1,4,5] Conversely, it has also been described that 50% of cT2N0 patients are pathologically downstaged, and correlation with pathologic T2N0 occurs in less than 10%. [2]…”

mentioning

confidence: 99%

Clinical T2N0 Esophageal Cancer: Identifying Pretreatment Characteristics Associated With Pathologic Upstaging and the Potential Role for Induction Therapy

Samson

Puri

Robinson

et al. 2016

The Annals of Thoracic Surgery

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Background While studies have suggested standard therapy for clinical T2N0 esophageal cancer should be primary surgery, we hypothesize there is a subgroup for whom induction therapy may result in improved overall survival (OS). Methods cT2N0 esophageal cancer patients receiving induction therapy or upfront esophagectomy (UE) were identified in the National Cancer Data Base (NCDB). UE patients were dichotomized as 1) pathologically upstaged or 2) same-or down-staged. Logistic regression models identified variables associated with upstaging and Kaplan-Meier analysis compared median OS. Results From 2006–2012, 932 (52.2%) cT2N0 patients received UE, while 853 (47.8%) received induction therapy first. 326/713 (45.7%) UE patients were upstaged. 87/326 (26.7%) patients had T upstaging, 98/326 (30.1%) had N upstaging, and 141/326 (43.3%) had both. Patients upstaged after UE had a higher tumor grade (35.1% versus 57.1% Grade 3), and a higher rate of lymphovascular invasion (LVI, 57.1% versus 17.7%), both p<0.001. Variables associated with upstaging included LVI (OR 6.0, 95% CI 2.9 – 12.5, p<0.001) and tumor grade 3 (OR 9.4, 1.8 – 48.4, p=0.007). Of upstaged UE patients, only 144 (44.2%) received adjuvant therapy. The median OS for cT2N0 patients upstaged after UE was 27.5 ± 2.5 months versus 43.9 ± 2.9 months for induction therapy patients (any resultant pathologic stage, p<0.001). Conclusions Half of all cT2N0 patients were pathologically upstaged after UE with worse survival compared to patients receiving induction therapy. Refining an upstaging model would help select patients for induction therapy and increase the rate of chemotherapy in patients at risk for systemic disease.

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“…Esophageal cancer has high morbidity and mortality, partly because patients tend to be diagnosed at an advanced stage and with esophageal obstruction, which seriously affects their quality of life. Thankfully, an effective medical treatment, PDT, has been found to relieve the esophageal obstruction by inducing localized tumor destruction via the photochemical generation of cytotoxic singlet oxygen [15][16][17][18][19].…”

Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin Increases the Sensitivity of Photodynamic Therapy Via NF-κB/HIF-1α/VEGF Pathway in Esophageal Cancer Cell in vitro and in vivo

Sui

Jiang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Although photodynamic therapy (PDT) can relieve esophageal obstruction and prolong survival time of patients with esophageal cancer, it can induce nuclear factor-kappa B (NF-κB) activation in many cancers, which plays a negative role in PDT. Dihydroartemisinin (DHA), the most potent artemisinin derivative, can enhance the effect of PDT on esophageal cancer cells. However, the mechanism is still unclear. Methods: We generated stable cell lines expressing the super-repressor form of the NF-κB inhibitor IκBα and cell lines with lentivirus vector-mediated silencing of the HIF-1α gene. Esophageal xenograft tumors were created by subcutaneous injection of Eca109 cells into BALB/c nude mice. Four treatment groups were analyzed: a control group, photosensitizer alone group, light alone group, and PDT group. NF-κB expression was detected by an electrophoretic mobility shift assay, hypoxia-inducible factor α (HIF-1α) and vascular endothelial growth factor (VEGF) by real-time PCR, NF-κB, HIF-1α, and VEGF protein by western blot, and Ki-67, HIF-1α, VEGF, and NF-κB protein by immunohistochemistry. Results: PDT increased NF-κB activity and the gene expression of HIF-1α and VEGF in vitro and in vivo. In contrast, the DHA groups, particularly the combined DHA and PDT treatment group, abolished the effect. The combined treatment significantly inhibited tumor growth in vitro and in vivo. NF-κB activity and HIF-1α expression were also reduced in the stable IκBα expression group, whereas the former showed no change in HIF-1α-silenced cells. Conclusion: DHA might increase the sensitivity of esophageal cancer cells to PDT by inhibiting the NF-κB/HIF-1α/VEGF pathway.

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Preoperative chemotherapy for resectable thoracic esophageal cancer

Cited by 92 publications

References 42 publications

Neoadjuvant Chemotherapy versus Chemoradiation Prior to Esophagectomy: Impact on Rate of Complete Pathologic Response and Survival in Esophageal Cancer Patients

Neoadjuvant Chemotherapy versus Chemoradiation Prior to Esophagectomy: Impact on Rate of Complete Pathologic Response and Survival in Esophageal Cancer Patients

Clinical T2N0 Esophageal Cancer: Identifying Pretreatment Characteristics Associated With Pathologic Upstaging and the Potential Role for Induction Therapy

Dihydroartemisinin Increases the Sensitivity of Photodynamic Therapy Via NF-κB/HIF-1α/VEGF Pathway in Esophageal Cancer Cell in vitro and in vivo

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