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Endoscopic and Imaging Predictors of Complete Pathologic Response After Chemoradiation for Esophageal Cancer

  • GI Oncology (R Bresalier, Section Editor)
  • Published:
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Abstract

Purpose of Review

Locally advanced esophageal cancer is frequently treated preoperatively with chemotherapy and radiation. The degree of response to this preoperative therapy varies in different patients, and a complete pathological response (pCR) has important implications in the management and prognosis of these patients. This is a review of the different modalities currently available to detect pCR and the clinical context of their use.

Recent Findings

While research is still ongoing, no single technique has emerged as the modality of choice to reliably predict pCR in all patients. Studies investigating the sensitivity, specificity, and accuracy of these modalities have had promising results, but no single modality has been firmly validated as the modality if choice. The emergence of functional imaging techniques and the use of biomarkers are newer developments which need further evaluation before adoption in routine clinical practice.

Summary

While no single technique reliably predicts pCR, a combination of imaging and diagnostic modalities (endoscopic appearance, biopsy, EUS, and PET/CT) may provide a better diagnostic yield rather than any of these modalities taken alone.

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References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F. GLOBOCAN 2012 v1.0 CIaMWICNI, Lyon FIAfRoCAfhgif. Accessed 19 Apr 2017.

  2. Arnold M, Soerjomataram I, Ferlay J, Forman D. Global incidence of oesophageal cancer by histological subtype in 2012. Gut. 2015;64(3):381–7. https://doi.org/10.1136/gutjnl-2014-308124.

    Article  PubMed  Google Scholar 

  3. Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349(23):2241–52. https://doi.org/10.1056/NEJMra035010.

    Article  CAS  PubMed  Google Scholar 

  4. Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R, et al. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol. 2008;26(7):1086–92. https://doi.org/10.1200/JCO.2007.12.9593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Van Hagen P, Hulshof MCCM, Van Lanschot JJB, Steyerberg EW, Van Berge Henegouwen MI, Wijnhoven BPL, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366(22):2074–84. https://doi.org/10.1056/NEJMoa1112088.

    Article  PubMed  Google Scholar 

  6. Gebski V, Burmeister B, Smithers BM, Foo K, Zalcberg J, Simes J. Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol. 2007;8(3):226–34. https://doi.org/10.1016/s1470-2045(07)70039-6.

    Article  CAS  PubMed  Google Scholar 

  7. Meredith KL, Weber JM, Turaga KK, Siegel EM, McLoughlin J, Hoffe S, et al. Pathologic response after neoadjuvant therapy is the major determinant of survival in patients with esophageal cancer. Ann Surg Oncol. 2010;17(4):1159–67. https://doi.org/10.1245/s10434-009-0862-1.

    Article  PubMed  Google Scholar 

  8. Brown WA, Thomas J, Gotley D, Burmeister BH, Lim KH, Martin I, et al. Use of oesophagogastroscopy to assess the response of oesophageal carcinoma to neoadjuvant therapy. Br J Surg. 2004;91(2):199–204. https://doi.org/10.1002/bjs.4411.

    Article  CAS  PubMed  Google Scholar 

  9. Schneider PM, Metzger R, Schaefer H, Baumgarten F, Vallbohmer D, Brabender J, et al. Response evaluation by endoscopy, rebiopsy, and endoscopic ultrasound does not accurately predict histopathologic regression after neoadjuvant chemoradiation for esophageal cancer. Ann Surg. 2008;248(6):902–8. https://doi.org/10.1097/SLA.0b013e31818f3afb.

    Article  PubMed  Google Scholar 

  10. Adelstein DJ, Rice TW, Becker M, Larto MA, Kirby TJ, Koka A, et al. Use of concurrent chemotherapy, accelerated fractionation radiation, and surgery for patients with esophageal carcinoma. Cancer. 1997;80(6):1011–20. https://doi.org/10.1002/(SICI)1097-0142(19970915)80:6<1011::AID-CNCR2>3.0.CO;2-C.

    Article  CAS  PubMed  Google Scholar 

  11. Vogel SB, Mendenhall WM, Sombeck MD, Marsh R, Woodward ER. Downstaging of esophageal cancer after preoperative radiation and chemotherapy. Ann Surg. 1995;221(6):685–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bates BA, Detterbeck FC, Bernard SA, Qaqish BF, Tepper JE. Concurrent radiation therapy and chemotherapy followed by esophagectomy for localized esophageal carcinoma. J Clin Oncol Off J Am Soc Clin Oncol. 1996;14(1):156–63. https://doi.org/10.1200/jco.1996.14.1.156.

    Article  CAS  Google Scholar 

  13. Cheedella NKS, Suzuki A, Xiao L, Hofstetter WL, Maru DM, Taketa T, et al. Association between clinical complete response and pathological complete response after preoperative chemoradiation in patients with gastroesophageal cancer: analysis in a large cohort. Ann Oncol. 2013;24(5):1262–6. https://doi.org/10.1093/annonc/mds617.

    Article  CAS  PubMed  Google Scholar 

  14. Yang Q, Cleary KR, Yao JC, Swisher SG, Roth JA, Lynch PM, et al. Significance of post-chemoradiation biopsy in predicting residual esophageal carcinoma in the surgical specimen. Dis Esophagus. 2004;17(1):38–43. https://doi.org/10.1111/j.1442-2050.2004.00355.x.

    Article  CAS  PubMed  Google Scholar 

  15. •• PSN VR, Goense L, Meziani J, Reitsma JB, Siersema PD, Vleggaar FP, et al. Endoscopic biopsy and EUS for the detection of pathologic complete response after neoadjuvant chemoradiotherapy in esophageal cancer: a systematic review and meta-analysis. Gastrointest Endosc. 2016;83(5):866–79. https://doi.org/10.1016/j.gie.2015.11.026. This is a meta-analysis which demonstrates that endoscopic rebiopsy and EUS, while specific, lack the sensitivity to reliably allow physicians to withhold surgery in patients with pCR after nCRT due to a very high false-negative rate

    Article  Google Scholar 

  16. Puli SR, Reddy JB, Bechtold ML, Antillon D, Ibdah JA, Antillon MR. Staging accuracy of esophageal cancer by endoscopic ultrasound: a meta-analysis and systematic review. World J Gastroenterol. 2008;14(10):1479–90.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Jost C, Binek J, Schuller JC, Bauerfeind P, Metzger U, Werth B, et al. Endosonographic radial tumor thickness after neoadjuvant chemoradiation therapy to predict response and survival in patients with locally advanced esophageal cancer: a prospective multicenter phase ll study by the Swiss Group for Clinical Cancer Research (SAKK 75/02). Gastrointest Endosc. 2010;71(7):1114–21. https://doi.org/10.1016/j.gie.2009.12.015.

    Article  PubMed  Google Scholar 

  18. Willis J, Cooper GS, Isenberg G, Sivak MV Jr, Levitan N, Clayman J, et al. Correlation of EUS measurement with pathologic assessment of neoadjuvant therapy response in esophageal carcinoma. Gastrointest Endosc. 2002;55(6):655–61.

    Article  PubMed  Google Scholar 

  19. Ota M, Murata Y, Ide H, Eguchi R, Nakumura T, Hayashi K, et al. Useful endoscopic ultrasonography to assess the efficacy of neoadjuvant therapy for advanced esophageal carcinoma: based on the response evaluation criteria in solid tumors. Dig Endosc. 2005;17(1):59–63. https://doi.org/10.1111/j.1443-1661.2005.00458.x.

    Article  Google Scholar 

  20. Isenberg G, Chak A, Canto MI, Levitan N, Clayman J, Pollack BJ, et al. Endoscopic ultrasound in restaging of esophageal cancer after neoadjuvant chemoradiation. Gastrointest Endosc. 1998;48(2):158–63.

    Article  CAS  PubMed  Google Scholar 

  21. Wieder HA, Brucher BL, Zimmermann F, Becker K, Lordick F, Beer A, et al. Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment. J Clin Oncol Off J Am Soc Clin Oncol. 2004;22(5):900–8. https://doi.org/10.1200/jco.2004.07.122.

    Article  CAS  Google Scholar 

  22. Molena D, Sun HH, Badr AS, Mungo B, Sarkaria IS, Adusumilli PS, et al. Clinical tools do not predict pathological complete response in patients with esophageal squamous cell cancer treated with definitive chemoradiotherapy. Dis Esophagus. 2014;27(4):355–9. https://doi.org/10.1111/dote.12126.

    Article  CAS  PubMed  Google Scholar 

  23. Swisher SG, Maish M, Erasmus JJ, Correa AM, Ajani JA, Bresalier R, et al. Utility of PET, CT, and EUS to identify pathologic responders in esophageal cancer. Ann Thorac Surg. 2004;78(4):1152–1160; discussion -60. https://doi.org/10.1016/j.athoracsur.2004.04.046.

    Article  PubMed  Google Scholar 

  24. Erasmus JJ, Munden RF, Truong MT, Ho JJ, Hofstetter WL, Macapinlac HA, et al. Preoperative chemo-radiation-induced ulceration in patients with esophageal cancer: a confounding factor in tumor response assessment in integrated computed tomographic-positron emission tomographic imaging. J Thorac Oncol. 2006;1(5):478–86.

    Article  PubMed  Google Scholar 

  25. van Rossum PS, Fried DV, Zhang L, Hofstetter WL, van Vulpen M, Meijer GJ, et al. The incremental value of subjective and quantitative assessment of 18F-FDG PET for the prediction of pathologic complete response to preoperative chemoradiotherapy in esophageal cancer. J Nucl Med. 2016;57(5):691–700. https://doi.org/10.2967/jnumed.115.163766.

    Article  PubMed  Google Scholar 

  26. Jones DR, Parker LA Jr, Detterbeck FC, Egan TM. Inadequacy of computed tomography in assessing patients with esophageal carcinoma after induction chemoradiotherapy. Cancer. 1999;85(5):1026–32.

    Article  CAS  PubMed  Google Scholar 

  27. Mandard A-M, Dalibard F, Mandard J-C, Marnay J, Henry-Amar M, Petiot J-F, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994;73(11):2680–6. https://doi.org/10.1002/1097-0142(19940601)73:11<2680::AID-CNCR2820731105>3.0.CO;2-C.

    Article  CAS  PubMed  Google Scholar 

  28. Djuric-Stefanovic A, Micev M, Stojanovic-Rundic S, Pesko P, Saranovic D. Absolute CT perfusion parameter values after the neoadjuvant chemoradiotherapy of the squamous cell esophageal carcinoma correlate with the histopathologic tumor regression grade. Eur J Radiol. 2015;84(12):2477–84. https://doi.org/10.1016/j.ejrad.2015.09.025.

    Article  CAS  PubMed  Google Scholar 

  29. •• van Rossum PS, van Lier AL, van Vulpen M, Reerink O, Lagendijk JJ, Lin SH, et al. Diffusion-weighted magnetic resonance imaging for the prediction of pathologic response to neoadjuvant chemoradiotherapy in esophageal cancer. Radiother Oncol. 2015;115(2):163–70. https://doi.org/10.1016/j.radonc.2015.04.027. This is a recent study evaluating functional imaging with DW-MRI and showed encouraging results with the use of tumor ADC change even in the first few weeks of nCRT, thus having the potential to limit its toxicity in non-responders

    Article  PubMed  Google Scholar 

  30. Ajani JA, Wang X, Song S, Suzuki A, Taketa T, Sudo K, et al. ALDH-1 expression levels predict response or resistance to preoperative chemoradiation in resectable esophageal cancer patients. Mol Oncol. 2014;8(1):142–9. https://doi.org/10.1016/j.molonc.2013.10.007.

    Article  CAS  PubMed  Google Scholar 

  31. Nakanoko T, Saeki H, Morita M, Nakashima Y, Ando K, Oki E, et al. Rad51 expression is a useful predictive factor for the efficacy of neoadjuvant chemoradiotherapy in squamous cell carcinoma of the esophagus. Ann Surg Oncol. 2014;21(2):597–604. https://doi.org/10.1245/s10434-013-3220-2.

    Article  PubMed  Google Scholar 

  32. •• Metzger R, Warnecke-Eberz U, Alakus H, Kutting F, Brabender J, Vallbohmer D, et al. Neoadjuvant radiochemotherapy in adenocarcinoma of the esophagus: ERCC1 gene polymorphisms for prediction of response and prognosis. J Gastrointest Surg. 2012;16(1):26–34. https://doi.org/10.1007/s11605-011-1700-x. This study evaluated the association of ERCC gene polymorphisms and histopathological response to nCRT in esophageal adenocarcinoma patients and showed that some genotypes were predictive of response to preoperative therapy

    Article  PubMed  Google Scholar 

  33. Tong Y-S, Zhou X-L, Wang X-W, Wu Q-Q, Yang T-X, Lv J, et al. Association of decreased expression of long non-coding RNA LOC285194 with chemoradiotherapy resistance and poor prognosis in esophageal squamous cell carcinoma. J Transl Med. 2014;12:233. https://doi.org/10.1186/s12967-014-0233-y.

    Article  PubMed  PubMed Central  Google Scholar 

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Author notes

  1. Guneesh S. Uberoi and Angad S. Uberoi contributed equally to the article and are joint first authors.

Authors and Affiliations

  1. Department of Gastroenterology, Hepatology and Nutrition-Unit 1466, UT MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030-4009, USA

    Guneesh S. Uberoi, Angad S. Uberoi & Manoop S. Bhutani

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  1. Guneesh S. Uberoi
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Correspondence to Manoop S. Bhutani.

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Manoop Bhutani, Angad Uberoi, and Guneesh Uberoi declare no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on GI Oncology

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Uberoi, G.S., Uberoi, A.S. & Bhutani, M.S. Endoscopic and Imaging Predictors of Complete Pathologic Response After Chemoradiation for Esophageal Cancer. Curr Gastroenterol Rep 19, 57 (2017). https://doi.org/10.1007/s11894-017-0594-5

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  • DOI: https://doi.org/10.1007/s11894-017-0594-5

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