The management of mid/distal esophageal and gastroesophageal junction (GEJ) cancer is challenging with only one-third patient presenting with a potentially resectable disease at diagnosis. Surgery alone treatments result in disappointing outcomes, and its utility as monotherapy has been challenged. Combined modality approach with the incorporation of neoadjuvant chemoradiation is the current standard of care for resectable patients, while definitive chemoradiation is used for locally advanced disease. The radiation techniques have evolved tremendously over past decade with the development of modern radiotherapy delivery techniques capable of safely delivering intensified treatment. This chapter provides a practical guide for evidence and treatment planning for radiation treatment strategies in the context of multimodality setting. The natural history and management of mid/lower esophageal cancer are not very different from GEJ (Siewert type I and II) cancers, and therefore, will be discussed together in this chapter.
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Matzinger O, et al. EORTC-ROG expert opinion: radiotherapy volume and treatment guidelines for neoadjuvant radiation of adenocarcinomas of the gastroesophageal junction and the stomach. Radiother Oncol. 2009;92(2):164–75.
Kelsen DP, et al. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med. 1998;339(27):1979–84.
Bosset JF, et al. Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med. 1997;337(3):161–7.
Hulscher JB, et al. Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus. N Engl J Med. 2002;347(21):1662–9.
Altorki N, et al. Three-field lymph node dissection for squamous cell and adenocarcinoma of the esophagus. Ann Surg. 2002;236(2):177–83.
National Comprehensive Cancer Network Clinical Practice Guideline in Oncology. Esophageal and esophagogastric junction cancers (version 2.2016). https://www.nccn.org/professionals/physician_gls/PDF/esophageal.pdf. Accessed 15 Dec 2016.
Stiles BM, Altorki NK. Traditional techniques of esophagectomy. Surg Clin North Am. 2012;92(5):1249–63.
Boshier PR, Anderson O, Hanna GB. Transthoracic versus transhiatal esophagectomy for the treatment of esophagogastric cancer: a meta-analysis. Ann Surg. 2011;254(6):894–906.
Chandrasekhara V, Ginsberg GG. Endoscopic mucosal resection: not your father’s polypectomy anymore. Gastroenterology. 2011;141(1):42–9.
Sykes AJ, et al. Radical radiotherapy for carcinoma of the oesophagus: an effective alternative to surgery. Radiother Oncol. 1998;48(1):15–21.
Earlam R, Cunha-Melo JR. Oesophogeal squamous cell carcinoms: II. A critical view of radiotherapy. Br J Surg. 1980;67(7):457–61.
Arnott SJ, et al. Low dose preoperative radiotherapy for carcinoma of the oesophagus: results of a randomized clinical trial. Radiother Oncol. 1992;24(2):108–13.
Gignoux M, et al. The value of preoperative radiotherapy in esophageal cancer: results of a study of the E.O.R.T.C. World J Surg. 1987;11(4):426–32.
Launois B, et al. Preoperative radiotherapy for carcinoma of the esophagus. Surg Gynecol Obstet. 1981;153(5):690–2.
Wang M, et al. Randomized clinical trial on the combination of preoperative irradiation and surgery in the treatment of esophageal carcinoma: report on 206 patients. Int J Radiat Oncol Biol Phys. 1989;16(2):325–7.
Arnott SJ, et al. Preoperative radiotherapy for esophageal carcinoma. Cochrane Database Syst Rev. 2005;4:CD001799.
Cooper JS, et al. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA. 1999;281(17):1623–7.
Herskovic A, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992;326(24):1593–8.
Minsky BD, et al. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol. 2002;20(5):1167–74.
Zhu LL, et al. A meta-analysis of concurrent chemoradiotherapy for advanced esophageal cancer. PLoS One. 2015;10(6):e0128616.
Urba SG, et al. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol. 2001;19(2):305–13.
Burmeister BH, et al. Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial. Lancet Oncol. 2005;6(9):659–68.
Walsh TN, et al. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996;335(7):462–7.
Tepper J, 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.
Sjoquist KM, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12(7):681–92.
van Hagen P, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366(22):2074–84.
Shapiro J, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015;16(9):1090–8.
Stahl M, et al. Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol. 2005;23(10):2310–7.
Macdonald JS, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345(10):725–30.
Ancona E, et al. Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone. Cancer. 2001;91(11):2165–74.
Kelsen DP, et al. Long-term results of RTOG trial 8911 (USA Intergroup 113): a random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer. J Clin Oncol. 2007;25(24):3719–25.
Medical Research Council Oesophageal Cancer Working Group. Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet. 2002;359(9319):1727–33.
Cunningham D, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11–20.
Allum WH, et al. Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J Clin Oncol. 2009;27(30):5062–7.
Ychou M, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29(13):1715–21.
Burmeister BH, et al. Is concurrent radiation therapy required in patients receiving preoperative chemotherapy for adenocarcinoma of the oesophagus? A randomised phase II trial. Eur J Cancer. 2011;47(3):354–60.
Conroy T, et al. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol. 2014;15(3):305–14.
Itakura Y, et al. Epidermal growth factor receptor overexpression in esophageal carcinoma. An immunohistochemical study correlated with clinicopathologic findings and DNA amplification. Cancer. 1994;74(3):795–804.
Lin G, et al. Epidermal growth factor receptor protein overexpression and gene amplification are associated with aggressive biological behaviors of esophageal squamous cell carcinoma. Oncol Lett. 2015;10(2):901–6.
Wilkinson NW, et al. Epidermal growth factor receptor expression correlates with histologic grade in resected esophageal adenocarcinoma. J Gastrointest Surg. 2004;8(4):448–53.
Crosby T, et al. Chemoradiotherapy with or without cetuximab in patients with oesophageal cancer (SCOPE1): a multicentre, phase 2/3 randomised trial. Lancet Oncol. 2013;14(7):627–37.
Waddell T, et al. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol. 2013;14(6):481–9.
Bendell JC, et al. A phase II trial of preoperative concurrent chemotherapy/radiation therapy plus bevacizumab/erlotinib in the treatment of localized esophageal cancer. Clin Adv Hematol Oncol. 2012;10(7):430–7.
You JJ, et al. Clinical utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in the staging of patients with potentially resectable esophageal cancer. J Thorac Oncol. 2013;8(12):1563–9.
Flanagan FL, et al. Staging of esophageal cancer with 18F-fluorodeoxyglucose positron emission tomography. Am J Roentgenol. 1997;168(2):417–24.
Moureau-Zabotto L, et al. Impact of CT and 18F-deoxyglucose positron emission tomography image fusion for conformal radiotherapy in esophageal carcinoma. Int J Radiat Oncol Biol Phys. 2005;63(2):340–5.
Hong TS, et al. Impact of manual and automated interpretation of fused PET/CT data on esophageal target definitions in radiation planning. Int J Radiat Oncol Biol Phys. 2008;72(5):1612–8.
Schreurs LM, et al. Impact of 18-fluorodeoxyglucose positron emission tomography on computed tomography defined target volumes in radiation treatment planning of esophageal cancer: reduction in geographic misses with equal inter-observer variability: PET/CT improves esophageal target definition. Dis Esophagus. 2010;23(6):493–501.
Gondi V, et al. Impact of hybrid fluorodeoxyglucose positron-emission tomography/computed tomography on radiotherapy planning in esophageal and non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2007;67(1):187–95.
Leong T, et al. A prospective study to evaluate the impact of FDG-PET on CT-based radiotherapy treatment planning for oesophageal cancer. Radiother Oncol. 2006;78(3):254–61.
Venkat P, Oliver J, Jin W, Almhanna K, Frakes JM, et al. Prognostic value of 18F-FDG PET/CT metabolic tumor volume for complete pathologic response and clinical outcomes after neoadjuvant chemoradiation therapy for locally advanced esophageal cancer. J Nucl Med Radiat Ther. 2016;7:308.
Cohen RJ, et al. Esophageal motion during radiotherapy: quantification and margin implications. Dis Esophagus. 2010;23(6):473–9.
Yaremko BP, et al. Determination of respiratory motion for distal esophagus cancer using four-dimensional computed tomography. Int J Radiat Oncol Biol Phys. 2008;70(1):145–53.
Guerrero T, et al. Intrathoracic tumour motion estimation from CT imaging using the 3D optical flow method. Phys Med Biol. 2004;49(17):4147–61.
Van De Voorde L, et al. The influence of gastric filling instructions on dose delivery in patients with oesophageal cancer: a prospective study. Radiother Oncol. 2015;117(3):442–7.
Bouchard M, McAleer MF, Starkschall G. Impact of gastric filling on radiation dose delivered to gastroesophageal junction tumors. Int J Radiat Oncol Biol Phys. 2010;77(1):292–300.
Patel AA, et al. Implications of respiratory motion as measured by four-dimensional computed tomography for radiation treatment planning of esophageal cancer. Int J Radiat Oncol Biol Phys. 2009;74(1):290–6.
Fernandez DC, et al. Stability of endoscopic ultrasound-guided fiducial marker placement for esophageal cancer target delineation and image-guided radiation therapy. Pract Radiat Oncol. 2013;3(1):32–9.
Gao XS, et al. Pathological analysis of clinical target volume margin for radiotherapy in patients with esophageal and gastroesophageal junction carcinoma. Int J Radiat Oncol Biol Phys. 2007;67(2):389–96.
Wu AJ, et al. Expert consensus contouring guidelines for intensity modulated radiation therapy in esophageal and gastroesophageal junction cancer. Int J Radiat Oncol Biol Phys. 2015;92(4):911–20.
Rice TW, Blackstone EH, Rusch VW. 7th edition of the AJCC cancer staging manual: esophagus and esophagogastric junction. Ann Surg Oncol. 2010;17(7):1721–4.
Swisher SG, et al. Final results of NRG oncology RTOG 0246: an organ-preserving selective resection strategy in esophageal cancer patients treated with definitive chemoradiation. J Thorac Oncol. 2017;12(2):368–74.
Ajani JA, et al. Phase II randomized trial of two nonoperative regimens of induction chemotherapy followed by chemoradiation in patients with localized carcinoma of the esophagus: RTOG 0113. J Clin Oncol. 2008;26(28):4551–6.
Lin SH, et al. Propensity score-based comparison of long-term outcomes with 3-dimensional conformal radiotherapy vs intensity-modulated radiotherapy for esophageal cancer. Int J Radiat Oncol Biol Phys. 2012;84(5):1078–85.
Chandra A, et al. Feasibility of using intensity-modulated radiotherapy to improve lung sparing in treatment planning for distal esophageal cancer. Radiother Oncol. 2005;77(3):247–53.
Ji FZ, et al. A randomized controlled trial of intensity-modulated radiation therapy plus docetaxel and cisplatin versus simple intensity-modulated radiation therapy in II-III stage esophageal carcinoma. Zhonghua Wei Chang Wai Ke Za Zhi. 2013;16(9):842–5.
Yaremko BP, et al. Adjuvant concurrent chemoradiation using intensity-modulated radiotherapy and simultaneous integrated boost for resected high-risk adenocarcinoma of the distal esophagus and gastro-esophageal junction. Radiat Oncol. 2013;8:33.
Hsu FM, et al. Association of clinical and dosimetric factors with postoperative pulmonary complications in esophageal cancer patients receiving intensity-modulated radiation therapy and concurrent chemotherapy followed by thoracic esophagectomy. Ann Surg Oncol. 2009;16(6):1669–77.
Freilich J, et al. Comparative outcomes for three-dimensional conformal versus intensity-modulated radiation therapy for esophageal cancer. Dis Esophagus. 2015;28(4):352–7.
Lin SH, et al. Radiation modality use and cardiopulmonary mortality risk in elderly patients with esophageal cancer. Cancer. 2016;122(6):917–28.
Chen YJ, et al. Helical tomotherapy for radiotherapy in esophageal cancer: a preferred plan with better conformal target coverage and more homogeneous dose distribution. Med Dosim. 2007;32(3):166–71.
Yin L, et al. Volumetric-modulated arc therapy vs. c-IMRT in esophageal cancer: a treatment planning comparison. World J Gastroenterol. 2012;18(37):5266–75.
Van Benthuysen L, Hales L, Podgorsak MB. Volumetric modulated arc therapy vs. IMRT for the treatment of distal esophageal cancer. Med Dosim. 2011;36(4):404–9.
Gong G, et al. Reduced lung dose during radiotherapy for thoracic esophageal carcinoma: VMAT combined with active breathing control for moderate DIBH. Radiat Oncol. 2013;8:291.
Patyal B. Dosimetry aspects of proton therapy. Technol Cancer Res Treat. 2007;6(4 Suppl):17–23.
Nguyen F, et al. Risk of a second malignant neoplasm after cancer in childhood treated with radiotherapy: correlation with the integral dose restricted to the irradiated fields. Int J Radiat Oncol Biol Phys. 2008;70(3):908–15.
Verma V, et al. Clinical outcomes and toxicities of proton radiotherapy for gastrointestinal neoplasms: a systematic review. J Gastrointest Oncol. 2016;7(4):644–64.
Chuong MD, et al. Improving outcomes for esophageal cancer using proton beam therapy. Int J Radiat Oncol Biol Phys. 2016;95(1):488–97.
Isacsson U, et al. Comparative treatment planning between proton and x-ray therapy in esophageal cancer. Int J Radiat Oncol Biol Phys. 1998;41(2):441–50.
Zhang X, et al. Four-dimensional computed tomography-based treatment planning for intensity-modulated radiation therapy and proton therapy for distal esophageal cancer. Int J Radiat Oncol Biol Phys. 2008;72(1):278–87.
Mizumoto M, et al. Clinical results of proton-beam therapy for locoregionally advanced esophageal cancer. Strahlenther Onkol. 2010;186(9):482–8.
Ishikawa H, et al. Proton beam therapy combined with concurrent chemotherapy for esophageal cancer. Anticancer Res. 2015;35(3):1757–62.
Lin SH, et al. Proton beam therapy and concurrent chemotherapy for esophageal cancer. Int J Radiat Oncol Biol Phys. 2012;83(3):e345–51.
Wang J, et al. Predictors of postoperative complications after trimodality therapy for esophageal cancer. Int J Radiat Oncol Biol Phys. 2013;86(5):885–91.
Pan X, et al. Impact of using different four-dimensional computed tomography data sets to design proton treatment plans for distal esophageal cancer. Int J Radiat Oncol Biol Phys. 2009;73(2):601–9.
Yu J, et al. Motion-robust intensity-modulated proton therapy for distal esophageal cancer. Med Phys. 2016;43(3):1111–8.
Brower JV, et al. Radiation dose escalation in esophageal cancer revisited: a contemporary analysis of the National Cancer Data Base, 2004 to 2012. Int J Radiat Oncol Biol Phys. 2016;96(5):985–93.
Marks LB, et al. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys. 2010;76(3):S10–9.
Gibbons JP, et al. Monitor unit calculations for external photon and electron beams: report of the AAPM Therapy Physics Committee Task Group No. 71. Med Phys. 2014;41(3):031501.
Stern RL, et al. Verification of monitor unit calculations for non-IMRT clinical radiotherapy: report of AAPM Task Group 114. Med Phys. 2011;38(1):504–30.
Ezzell GA, et al. Guidance document on delivery, treatment planning, and clinical implementation of IMRT: report of the IMRT subcommittee of the AAPM radiation therapy committee. Med Phys. 2003;30(8):2089–115.
Low DA, et al. Dosimetry tools and techniques for IMRT. Med Phys. 2011;38(3):1313–38.
Klein EE, et al. Task Group 142 report: quality assurance of medical accelerators. Med Phys. 2009;36(9):4197–212.
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Rishi, A., Chuong, M.D., Frakes, J.M. (2018). Mid/Distal Esophageal Cancer and Gastroesophageal Junction Cancer (Siewert Type I and II). In: Russo, S., Hoffe, S., Kim, E. (eds) Gastrointestinal Malignancies. Practical Guides in Radiation Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-64900-9_2
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