Immunohistochemical prognostic markers of esophageal squamous cell carcinoma:a systematic review

Background: Esophageal squamous cell carcinoma(ESCC) is an aggressive malignancy, with a high incidence and poor prognosis. In the past several decades, hundreds of proteins have been reported to be associated with the prognosis of ESCC, but none has been widely accepted to guide clinical care. This study aimed to identify proteins with great potential for predicting prognosis of ESCC.Methods: We conducted a systematic review on immunohistochemical(IHC) prognostic markers of ESCC according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) Guidelines. Literature related to IHC prognostic markers of ESCC were searched from PubMed, Embase, Web of Science, and Cochrane Library until January 30 th, 2017. The risk of bias of these original studies was evaluated using the Quality in Prognosis Studies(QUIPS) tool.Results: We identified 11 emerging IHC markers with reproducible results, including eight markers [epidermal growth factor receptor(EGFR), Cyclin D1, vascular endothelial growth factor(VEGF), Survivin, Podoplanin, Fascin,phosphorylated mammalian target of rapamycin(p-mTOR), and pyruvate kinase M2(PKM2)] indicating unfavorable prognosis and 3 markers(P27, P16, and E-cadherin) indicating favorable prognosis of ESCC.Conclusion: Strong evidence supports that these 11 emerging IHC markers or their combinations may be useful in predicting prognosis and aiding personalized therapy decision-making for ESCC patients.

Dose escalation guided by^(18)F-FDG PET/CT for esophageal cancer

Objective:To assess the feasibility of dose escalation guided by ^(18)F-deoxyglucose positron emission tomography/computer tomography(^(18)F-FDG PET/CT)for esophageal cancer(EC).Methods and materials:Ten random patients treated with definitive chemoradiotherapy and pre-therapeutic ^(18)FFDG PET/CT were included in this study.Retrospectively,a threshold of 50%of SUVmax was used to define the high FDG uptake region of the GTV(GTVPET).Three intensity-modulated radiation therapy(IMRT)plans were generated,delivering three dose levels to three different planning target volumes(PTVs).50.4 Gy delivered to PTV50.4 was defined on computed tomography(CT)as Plan50.4,63 Gy was delivered to PTV63 was defined as GTV plus a uniform margin of 0.5 cm as Plan63,and 70 Gy delivered to PTV70 was defined as GTVPET plus a 0.5 cm margin as Plan70.A dosimetric comparison was performed based on normal tissue complication probability(NTCP)for the lung and heart.Results:Clinically acceptable dose escalation failed for 2 of 10 patients in Plan63 due to heart dose constraints.One patient failed heart dose constraint for Plan70.Two patients failed spinal cord constraint for Plan63.Three patients failed lung dose constraints for both Plan63 and Plan70,two of which were even not suitable for Plan50.4 for the same reason.NTCP modeling for lung showed increased risk for Plan63 and Plan70 compared to Plan50.4.The difference between Plan63 and Plan70 was insignificant.NTCP modeling for heart showed an increased risk from 6.38%of Plan50.4 to 8.88%of Plan70(P=0.009)or 9.79%of Plan63(P=0.007).The risk of heart mortality was significantly higher for Plan63 than Plan70(P=0.047).Conclusions:Selective boosting of sub-volumes based on ^(18)F-FDG PET/CT is feasible way with a modest increase in the risk of cardiac and lung toxicities.