Oesophageal cancer is the sixth most common cause of cancer-related death worldwide and is therefore a major global health challenge. The two major subtypes of oesophageal cancer are oesophageal squamous cell carcinoma (OSCC) and oesophageal adenocarcinoma (OAC), which are epidemiologically and biologically distinct. OSCC accounts for 90% of all cases of oesophageal cancer globally and is highly prevalent in the East, East Africa and South America. OAC is more common in developed countries than in developing countries. Preneoplastic lesions are identifiable for both OSCC and OAC; these are frequently amenable to endoscopic ablative therapies. Most patients with oesophageal cancer require extensive treatment, including chemotherapy, chemoradiotherapy and/or surgical resection. Patients with advanced or metastatic oesophageal cancer are treated with palliative chemotherapy; those who are human epidermal growth factor receptor 2 (HER2)-positive may also benefit from trastuzumab treatment. Immuno-oncology therapies have also shown promising early results in OSCC and OAC. In this Primer, we review state-of-the-art knowledge on the biology and treatment of oesophageal cancer, including screening, endoscopic ablative therapies and emerging molecular targets, and we discuss best practices in chemotherapy, chemoradiotherapy, surgery and the maintenance of patient quality of life.
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Lin, Y. et al. Epidemiology of esophageal cancer in Japan and China. J. Epidemiol. 23, 233–242 (2013).
Cook, M. B., Chow, W. H. & Devesa, S. S. Oesophageal cancer incidence in the United States by race, sex, and histologic type, 1977–2005. Br. J. Cancer 101, 855–859 (2009).
Arnold, M., Soerjomataram, I., Ferlay, J. & Forman, D. Global incidence of oesophageal cancer by histological subtype in 2012. Gut 64, 381–387 (2015).
The Cancer Genome Atlas Research Network. Integrated genomic characterization of oesophageal carcinoma. Nature 541, 169–175 (2017). A comprehensive multiplatform analysis of the molecular biology of OSCC and OAC.
Fitzgerald, R. C. et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus. Gut 63, 7–42 (2014). Guidelines that discuss the endoscopic management of Barrett oesophagus.
Lordick, F., Mariette, C., Haustermans, K., Obermannova, R. & Arnold, D. Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 27, v50–v57 (2016).
National Comprehensive Cancer Network. NCCN guidelines for patients — esophageal cancer. NCCNhttps://www.nccn.org/patients/guidelines/esophageal/files/assets/common/downloads/files/esophageal.pdf (2016).
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. 14, 481–489 (2013).
Lordick, F. et al. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 14, 490–499 (2013).
Shah, M. A. et al. Effect of fluorouracil, leucovorin, and oxaliplatin with or without onartuzumab in HER2-negative, MET-positive gastroesophageal adenocarcinoma: the METGastric randomized clinical trial. JAMA Oncol. 3, 620–627 (2017).
Cunningham, D. et al. Phase III, randomized, double-blind, multicenter, placebo (P)-controlled trial of rilotumumab (R) plus epirubicin, cisplatin and capecitabine (ECX) as first-line therapy in patients (pts) with advanced MET-positive (pos) gastric or gastroesophageal junction (G/GEJ) cancer: RILOMET-1 study. J. Clin. Oncol. 33, 4000 (2015).
Backemar, L., Wikman, A., Djarv, T., Johar, A. & Lagergren, P. Co-morbidity after oesophageal cancer surgery and recovery of health-related quality of life. Br. J. Surg. 103, 1665–1675 (2016).
Anandavadivelan, P. & Lagergren, P. Cachexia in patients with oesophageal cancer. Nat. Rev. Clin. Oncol. 13, 185–198 (2016). A comprehensive review of the nutritional problems observed in patients with oesophageal cancer.
Siegel, R., Ma, J., Zou, Z. & Jemal, A. Cancer statistics, 2014. CA Cancer J. Clin. 64, 9–29 (2014).
Cancer Research UK. Oesophageal cancer statistics. Cancer Research UKhttp://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/oesophageal-cancer (2017).
Trivers, K. F., Sabatino, S. A. & Stewart, S. L. Trends in esophageal cancer incidence by histology, United States, 1998–2003. Int. J. Cancer 123, 1422–1428 (2008).
Zhao, J., He, Y. T., Zheng, R. S., Zhang, S. W. & Chen, W. Q. Analysis of esophageal cancer time trends in China, 1989–2008. Asian Pac. J. Cancer Prev. 13, 4613–4617 (2012).
He, Y. T. et al. Trends in incidence of esophageal and gastric cardia cancer in high-risk areas in China. Eur. J. Cancer Prev. 17, 71–76 (2008).
Wei, W. Q. et al. Long-term follow-up of a community assignment, one-time endoscopic screening study of esophageal cancer in China. J. Clin. Oncol. 33, 1951–1957 (2015).
Edgren, G., Adami, H.-O., Weiderpass Vainio, E. & Nyrén, O. A global assessment of the oesophageal adenocarcinoma epidemic. Gut 62, 1406–1414 (2013).
Freedman, N. D. et al. A prospective study of tobacco, alcohol, and the risk of esophageal and gastric cancer subtypes. Am. J. Epidemiol. 165, 1424–1433 (2007).
Tran, G. D. et al. Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China. Int. J. Cancer 113, 456–463 (2005).
Yang, C. X. et al. Esophageal cancer risk by ALDH2 and ADH2 polymorphisms and alcohol consumption: exploration of gene–environment and gene–gene interactions. Asian Pac. J. Cancer Prev. 6, 256–262 (2005).
Prabhu, A., Obi, K. O. & Rubenstein, J. H. The synergistic effects of alcohol and tobacco consumption on the risk of esophageal squamous cell carcinoma: a meta-analysis. Am. J. Gastroenterol. 109, 822–827 (2014).
Freedman, N. D. et al. Fruit and vegetable intake and esophageal cancer in a large prospective cohort study. Int. J. Cancer 121, 2753–2760 (2007).
Yang, C. S. et al. Vitamin A and other deficiencies in Linxian, a high esophageal cancer incidence area in northern China. J. Natl Cancer Inst. 73, 1449–1453 (1984).
Taylor, P. R. et al. Prospective study of serum vitamin E levels and esophageal and gastric cancers. J. Natl Cancer Inst. 95, 1414–1416 (2003).
Cooper, S. C. et al. The influence of deprivation and ethnicity on the incidence of esophageal cancer in England. Cancer Causes Control 20, 1459–1467 (2009).
Islami, F. et al. High-temperature beverages and foods and esophageal cancer risk — a systematic review. Int. J. Cancer 125, 491–524 (2009).
Ludmir, E. B., Stephens, S. J., Palta, M., Willett, C. G. & Czito, B. G. Human papillomavirus tumor infection in esophageal squamous cell carcinoma. J. Gastrointest. Oncol. 6, 287–295 (2015).
Blaydon, D. C. et al. RHBDF2 mutations are associated with tylosis, a familial esophageal cancer syndrome. Am. J. Hum. Genet. 90, 340–346 (2012).
Wang, L. D. et al. Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54. Nat. Genet. 42, 759–763 (2010).
Abnet, C. C. et al. A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma. Nat. Genet. 42, 764–767 (2010).
Wu, C. et al. Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations. Nat. Genet. 46, 1001–1006 (2014).
Cui, R. et al. Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhance esophageal cancer risk. Gastroenterology 137, 1768–1775 (2009).
Liu, X. et al. Genetic alterations in esophageal tissues from squamous dysplasia to carcinoma. Gastroenterology 153, 166–177 (2017).
Fagundes, R. B., Melo, C. R., Putten, A. C., Moreira, L. F. & de Barros, S. G. p53 immunoexpression: an aid to conventional methods in the screening of precursor lesions of squamous esophageal cancer in patients at high-risk? Cancer Detect. Prev. 29, 227–232 (2005).
Muller, L. B. et al. Stepwise expression of CDKN2A and RB1 proteins in esophageal mucosa from patients at high risk for squamous cell carcinoma. Appl. Immunohistochem. Mol. Morphol. 22, 669–673 (2014).
Couch, G. et al. The discovery and validation of biomarkers for the diagnosis of esophageal squamous dysplasia and squamous cell carcinoma. Cancer Prev. Res. (Phila.) 9, 558–566 (2016).
Song, Y. et al. Identification of genomic alterations in oesophageal squamous cell cancer. Nature 509, 91–95 (2014).
Gao, Y. B. et al. Genetic landscape of esophageal squamous cell carcinoma. Nat. Genet. 46, 1097–1102 (2014).
Lin, D. C. et al. Genomic and molecular characterization of esophageal squamous cell carcinoma. Nat. Genet. 46, 467–473 (2014).
Anderson, L. A. et al. Risk factors for Barrett's oesophagus and oesophageal adenocarcinoma: results from the FINBAR study. World J. Gastroenterol. 13, 1585–1594 (2007).
Cook, M. B. et al. Gastroesophageal reflux in relation to adenocarcinomas of the esophagus: a pooled analysis from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). PLoS ONE 9, e103508 (2014).
Stein, D. J., El-Serag, H. B., Kuczynski, J., Kramer, J. R. & Sampliner, R. E. The association of body mass index with Barrett's oesophagus. Aliment. Pharmacol. Ther. 22, 1005–1010 (2005).
Akiyama, T. et al. Visceral obesity and the risk of Barrett's esophagus in Japanese patients with non-alcoholic fatty liver disease. BMC Gastroenterol. 9, 56 (2009).
Leggett, C. L. et al. Metabolic syndrome as a risk factor for Barrett esophagus: a population-based case–control study. Mayo Clin. Proc. 88, 157–165 (2013).
Cook, M. B. et al. Cigarette smoking and adenocarcinomas of the esophagus and esophagogastric junction: a pooled analysis from the international BEACON consortium. J. Natl Cancer Inst. 102, 1344–1353 (2010).
Thrift, A. P., Kramer, J. R., Richardson, P. A. & El-Serag, H. B. No significant effects of smoking or alcohol consumption on risk of Barrett's esophagus. Dig. Dis. Sci. 59, 108–116 (2014).
Jiao, L. et al. Dietary consumption of meat, fat, animal products and advanced glycation end-products and the risk of Barrett's oesophagus. Aliment. Pharmacol. Ther. 38, 817–824 (2013).
Kubo, A. et al. Dietary antioxidants, fruits, and vegetables and the risk of Barrett's esophagus. Am. J. Gastroenterol. 103, 1614–1623 (2008).
Thrift, A. P. et al. Helicobacter pylori infection and the risks of Barrett's oesophagus: a population-based case–control study. Int. J. Cancer 130, 2407–2416 (2012).
Islami, F. & Kamangar, F. Helicobacter pylori and esophageal cancer risk: a meta-analysis. Cancer Prev. Res. (Phila.) 1, 329–338 (2008).
Verbeek, R. E. et al. Familial clustering of Barrett's esophagus and esophageal adenocarcinoma in a European cohort. Clin. Gastroenterol. Hepatol. 12, 1656–1663.e1 (2014).
Chak, A. et al. Familiality in Barrett's esophagus, adenocarcinoma of the esophagus, and adenocarcinoma of the gastroesophageal junction. Cancer Epidemiol. Biomarkers Prev. 15, 1668–1673 (2006).
Vaughan, T. L. & Fitzgerald, R. C. Precision prevention of oesophageal adenocarcinoma. Nat. Rev. Gastroenterol. Hepatol. 12, 243–248 (2015).
Su, Z. et al. Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus. Nat. Genet. 44, 1131–1136 (2012).
Gharahkhani, P. et al. Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis. Lancet Oncol. 17, 1363–1373 (2016).
Buas, M. F. et al. Germline variation in inflammation-related pathways and risk of Barrett's oesophagus and oesophageal adenocarcinoma. Guthttp://dx.doi.org/10.1136/gutjnl-2016-311622 (2016).
Dai, J. Y. et al. A newly identified susceptibility locus near FOXP1 modifies the association of gastroesophageal reflux with Barrett's esophagus. Cancer Epidemiol. Biomarkers Prev. 24, 1739–1747 (2015).
Dvorak, K. et al. Molecular mechanisms of Barrett's esophagus and adenocarcinoma. Ann. NY Acad. Sci. 1232, 381–391 (2011).
Vaninetti, N. M. et al. Inducible nitric oxide synthase, nitrotyrosine and p53 mutations in the molecular pathogenesis of Barrett's esophagus and esophageal adenocarcinoma. Mol. Carcinog. 47, 275–285 (2008).
Dulak, A. M. et al. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat. Genet. 45, 478–486 (2013).
Quante, M. et al. Bile acid and inflammation activate gastric cardia stem cells in a mouse model of Barrett-like metaplasia. Cancer Cell 21, 36–51 (2012).
Wang, X. et al. Residual embryonic cells as precursors of a Barrett's-like metaplasia. Cell 145, 1023–1035 (2011).
di Pietro, M., Alzoubaidi, D. & Fitzgerald, R. C. Barrett's esophagus and cancer risk: how research advances can impact clinical practice. Gut Liver 8, 356–370 (2014).
Bansal, A. & Fitzgerald, R. C. Biomarkers in Barrett's esophagus: role in diagnosis, risk stratification, and prediction of response to therapy. Gastroenterol. Clin. North Am. 44, 373–390 (2015).
Duits, L. C. et al. Barrett's oesophagus patients with low-grade dysplasia can be accurately risk-stratified after histological review by an expert pathology panel. Gut 64, 700–706 (2015).
Weaver, J. M. J. et al. Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis. Nat. Genet. 46, 837–843 (2014).
Stachler, M. D. et al. Paired exome analysis of Barrett's esophagus and adenocarcinoma. Nat. Genet. 47, 1047–1055 (2015).
Reid, B. J. et al. Predictors of progression in Barrett's esophagus II: baseline 17p (p53) loss of heterozygosity identifies a patient subset at increased risk for neoplastic progression. Am. J. Gastroenterol. 96, 2839–2848 (2001).
Galipeau, P. C., Prevo, L. J., Sanchez, C. A., Longton, G. M. & Reid, B. J. Clonal expansion and loss of heterozygosity at chromosomes 9p and 17p in premalignant esophageal (Barrett's) tissue. J. Natl Cancer Inst. 91, 2087–2095 (1999).
Ross-Innes, C. S. et al. Whole-genome sequencing provides new insights into the clonal architecture of Barrett's esophagus and esophageal adenocarcinoma. Nat. Genet. 47, 1038–1046 (2015).
Maley, C. C. et al. Genetic clonal diversity predicts progression to esophageal adenocarcinoma. Nat. Genet. 38, 468–473 (2006).
Martinez, P. et al. Dynamic clonal equilibrium and predetermined cancer risk in Barrett's oesophagus. Nat. Commun. 7, 12158 (2016).
Ross-Innes, C. S. et al. Risk stratification of Barrett's oesophagus using a non-endoscopic sampling method coupled with a biomarker panel: a cohort study. Lancet Gastroenterol. Hepatol. 2, 23–31 (2017).
Xu, E. et al. Genome-wide methylation analysis shows similar patterns in Barrett's esophagus and esophageal adenocarcinoma. Carcinogenesis 34, 2750–2756 (2013).
Wong, D. J., Barrett, M. T., Stoger, R., Emond, M. J. & Reid, B. J. p16INK4a promoter is hypermethylated at a high frequency in esophageal adenocarcinomas. Cancer Res. 57, 2619–2622 (1997).
Klump, B., Hsieh, C. J., Holzmann, K., Gregor, M. & Porschen, R. Hypermethylation of the CDKN2/p16 promoter during neoplastic progression in Barrett's esophagus. Gastroenterology 115, 1381–1386 (1998).
Alexandrov, L. B. et al. Signatures of mutational processes in human cancer. Nature 500, 415–421 (2013).
Agrawal, N. et al. Comparative genomic analysis of esophageal adenocarcinoma and squamous cell carcinoma. Cancer Discov. 2, 899–905 (2012).
Dulak, A. M. et al. Gastrointestinal adenocarcinomas of the esophagus, stomach and colon exhibit distinct patterns of genome instability and oncogenesis. Cancer Res. 72, 4383–4393 (2012).
Deng, N. et al. A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. Gut 61, 673–684 (2012).
Secrier, M. et al. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance. Nat. Genet. 48, 1131–1141 (2016). A study that defines clinically relevant subgroups of OAC using whole-genome sequencing.
Kwak, E. L. et al. Clinical activity of AMG 337, an oral MET kinase inhibitor, in adult patients (pts) with MET-amplified gastroesophageal junction (GEJ), gastric (G), or esophageal (E) cancer. J. Clin. Oncol. 33, 1 (2015).
Paterson, A. L. et al. Characterization of the timing and prevalence of receptor tyrosine kinase expression changes in oesophageal carcinogenesis. J. Pathol. 230, 118–128 (2013).
Morita, F. H. et al. Narrow band imaging versus lugol chromoendoscopy to diagnose squamous cell carcinoma of the esophagus: a systematic review and meta-analysis. BMC Cancer 17, 54 (2017).
Graham, D. Y., Schwartz, J. T., Cain, G. D. & Gyorkey, F. Prospective evaluation of biopsy number in the diagnosis of esophageal and gastric carcinoma. Gastroenterology 82, 228–231 (1982).
Bosman, F. T., Carneiro, F., Hruban, R. H. & Theise, N. D. (eds) WHO Classification of Tumours of the Digestive System (IARC, 2010).
Wong, H. H. & Chu, P. Immunohistochemical features of the gastrointestinal tract tumors. J. Gastrointest. Oncol. 3, 262–284 (2012).
Amin, M. B. et al. (eds) AJCC Cancer Staging Manual 8th edn (Springer International Publishing, 2017).
Puli, S.-R. et al. Staging accuracy of esophageal cancer by endoscopic ultrasound: a meta-analysis and systematic review. World J. Gastroenterol. 14, 1479–1490 (2008).
Seevaratnam, R. et al. How useful is preoperative imaging for tumor, node, metastasis (TNM) staging of gastric cancer? A meta-analysis. Gastric Cancer 15 (Suppl. 1), S3–S18 (2012).
Findlay, J. M. et al. Pragmatic staging of oesophageal cancer using decision theory involving selective endoscopic ultrasonography, PET and laparoscopy. Br. J. Surg. 102, 1488–1499 (2015).
Smyth, E. et al. A prospective evaluation of the utility of 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography and computed tomography in staging locally advanced gastric cancer. Cancer 118, 5481–5488 (2012).
de Graaf, G. W., Ayantunde, A. A., Parsons, S. L., Duffy, J. P. & Welch, N. T. The role of staging laparoscopy in oesophagogastric cancers. Eur. J. Surg. Oncol. 33, 988–992 (2007).
Weber, W. A. et al. Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J. Clin. Oncol. 19, 3058–3065 (2001).
Ott, K. et al. Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction. J. Clin. Oncol. 24, 4692–4698 (2006).
Lordick, F. et al. PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol. 8, 797–805 (2007).
zum Büschenfelde, C. M. et al. 18F-FDG PET-guided salvage neoadjuvant radiochemotherapy of adenocarcinoma of the esophagogastric junction: the MUNICON II trial. J. Nucl. Med. 52, 1189–1196 (2011).
Goodman, K., Niedzwiecki, D. & Hall, N. Initial results of CALGB 80803 (Alliance): a randomized phase II trial of PET scan-directed combined modality therapy for esophageal cancer. J. Clin Oncol. 35, 1 (2017).
Torre, L. A. et al. Global cancer statistics, 2012. CA Cancer J. Clin. 65, 87–108 (2015).
Shaheen, N. J., Falk, G. W., Iyer, P. G. & Gerson, L. B. ACG clinical guideline: diagnosis and management of Barrett's esophagus. Am. J. Gastroenterol. 111, 30–50 (2016).
Shariff, M. K. et al. Randomized crossover study comparing efficacy of transnasal endoscopy with that of standard endoscopy to detect Barrett's esophagus. Gastrointest. Endosc. 75, 954–961 (2012).
Alashkar, B. et al. Development of a program to train physician extenders to perform transnasal esophagoscopy and screen for Barrett's esophagus. Clin. Gastroenterol. Hepatol. 12, 785–792 (2014).
Bhardwaj, A., Hollenbeak, C. S., Pooran, N. & Mathew, A. A meta-analysis of the diagnostic accuracy of esophageal capsule endoscopy for Barrett's esophagus in patients with gastroesophageal reflux disease. Am. J. Gastroenterol. 104, 1533–1539 (2009).
Kadri, S. R. et al. Acceptability and accuracy of a non-endoscopic screening test for Barrett's oesophagus in primary care: cohort study. BMJ 341, c4372 (2010).
Ross-Innes, C. S. et al. Evaluation of a minimally invasive cell sampling device coupled with assessment of trefoil factor 3 expression for diagnosing Barrett's esophagus: a multi-center case–control study. PLoS Med. 12, e1001780 (2015). A study that screened patients for Barrett oesophagus using the minimally invasive Cytosponge and biomarker stratification.
ISRCTN registry. BEST3 — a trial of a new GP-based test for patients with heartburn symptoms. ISRCTNhttp://www.isrctn.com/ISRCTN68382401 (2017).
Desai, T. K. et al. The incidence of oesophageal adenocarcinoma in non-dysplastic Barrett's oesophagus: a meta-analysis. Gut 61, 970–976 (2012).
Singh, S. et al. Incidence of esophageal adenocarcinoma in Barrett's esophagus with low-grade dysplasia: a systematic review and meta-analysis. Gastrointest. Endosc. 79, 897–909.e4 (2014).
Rastogi, A. et al. Incidence of esophageal adenocarcinoma in patients with Barrett's esophagus and high-grade dysplasia: a meta-analysis. Gastrointestinal Endosc. 67, 394–398 (2008).
Hvid-Jensen, F., Pedersen, L., Drewes, A. M., Sorensen, H. T. & Funch-Jensen, P. Incidence of adenocarcinoma among patients with Barrett's esophagus. N. Engl. J. Med. 365, 1375–1383 (2011).
Kastelein, F. et al. Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett's oesophagus. Gut 62, 1676–1683 (2013).
Sikkema, M. et al. Aneuploidy and overexpression of Ki67 and p53 as markers for neoplastic progression in Barrett's esophagus: a case–control study. Am. J. Gastroenterol. 104, 2673–2680 (2009).
Maret-Ouda, J., Konings, P., Lagergren, J. & Brusselaers, N. Antireflux surgery and risk of esophageal adenocarcinoma: a systematic review and meta-analysis. Ann. Surg. 263, 251–257 (2016).
Kastelein, F. et al. Proton pump inhibitors reduce the risk of neoplastic progression in patients with Barrett's esophagus. Clin. Gastroenterol. Hepatol. 11, 382–388 (2013).
Nguyen, D. M. et al. Medication usage and the risk of neoplasia in patients with Barrett's esophagus. Clin. Gastroenterol. Hepatol. 7, 1299–1304 (2009).
Hillman, L. C., Chiragakis, L., Shadbolt, B., Kaye, G. L. & Clarke, A. C. Proton-pump inhibitor therapy and the development of dysplasia in patients with Barrett's oesophagus. Med. J. Aust. 180, 387–391 (2004).
Brasky, T. M. et al. Non-steroidal anti-inflammatory drugs and cancer risk in women: results from the Women's Health Initiative. Int. J. Cancer 135, 1869–1883 (2014).
Cao, Y. et al. Population-wide impact of long-term use of aspirin and the risk for cancer. JAMA Oncol. 2, 762–769 (2016).
Corley, D. A., Kerlikowske, K., Verma, R. & Buffler, P. Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and meta-analysis. Gastroenterology 124, 47–56 (2003).
US National Library of Medicine. ClinicalTrials.govhttps://clinicaltrials.gov/ct2/show/NCT00357682 (2016).
Shaheen, N. J. et al. Radiofrequency ablation in Barrett's esophagus with dysplasia. N. Engl. J. Med. 360, 2277–2288 (2009).
Prasad, G. A. et al. Long-term survival following endoscopic and surgical treatment of high-grade dysplasia in Barrett's esophagus. Gastroenterology 132, 1226–1233 (2007).
Phoa, K. N. et al. Radiofrequency ablation versus endoscopic surveillance for patients with Barrett esophagus and low-grade dysplasia: a randomized clinical trial. JAMA 311, 1209–1217 (2014).
Pech, O. et al. Long-term results and risk factor analysis for recurrence after curative endoscopic therapy in 349 patients with high-grade intraepithelial neoplasia and mucosal adenocarcinoma in Barrett's oesophagus. Gut 57, 1200–1206 (2008).
Manner, H. et al. Efficacy, safety, and long-term results of endoscopic treatment for early stage adenocarcinoma of the esophagus with low-risk sm1 invasion. Clin. Gastroenterol. Hepatol. 11, 630–635 (2013).
He, S. et al. Endoscopic radiofrequency ablation for early esophageal squamous cell neoplasia: report of safety and effectiveness from a large prospective trial. Endoscopy 47, 398–408 (2015).
Haidry, R. J. et al. Radiofrequency ablation for early oesophageal squamous neoplasia: outcomes form United Kingdom registry. World J. Gastroenterol. 19, 6011–6019 (2013).
Bergman, J. J. et al. Outcomes from a prospective trial of endoscopic radiofrequency ablation of early squamous cell neoplasia of the esophagus. Gastrointest. Endosc. 74, 1181–1190 (2011).
Blot, W. J. et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J. Natl Cancer Inst. 85, 1483–1492 (1993).
Sun, L. & Yu, S. Meta-analysis: non-steroidal anti-inflammatory drug use and the risk of esophageal squamous cell carcinoma. Dis. Esophagus 24, 544–549 (2011).
Rutegård, M. et al. Population-based esophageal cancer survival after resection without neoadjuvant therapy: an update. Surgery 152, 903–910 (2012).
Pech, O. et al. Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus. Gastroenterology 146, 652–660.e1 (2014).
Desai, M. et al. Efficacy and safety outcomes of multimodal endoscopic eradication therapy in Barrett's esophagus-related neoplasia: a systematic review and pooled analysis. Gastrointest. Endosc. 85, 482–495.e4 (2017).
Merkow, R. P. et al. Treatment trends, risk of lymph node metastasis, and outcomes for localized esophageal cancer. J. Natl Cancer Inst. 106, dju133 (2014).
Boys, J. A. et al. Can the risk of lymph node metastases be gauged in endoscopically resected submucosal esophageal adenocarcinomas? A multi-center study. J. Gastrointest. Surg. 20, 6–12 (2016).
Haverkamp, L., Ruurda, J. P., van Leeuwen, M. S., Siersema, P. D. & van Hillegersberg, R. Systematic review of the surgical strategies of adenocarcinomas of the gastroesophageal junction. Surg. Oncol. 23, 222–228 (2014).
Martin, J. T., Mahan, A., Zwischenberger, J. B., McGrath, P. C. & Tzeng, C. W. Should gastric cardia cancers be treated with esophagectomy or total gastrectomy? A comprehensive analysis of 4,996 NSQIP/SEER patients. J. Am. Coll. Surg. 220, 510–520 (2015).
Wei, M. T. et al. Transthoracic versus transhiatal surgery for cancer of the esophagogastric junction: a meta-analysis. World J. Gastroenterol. 20, 10183–10192 (2014).
Aurello, P. et al. Transthoracically or transabdominally: how to approach adenocarcinoma of the distal esophagus and cardia. A meta-analysis. Tumori 102, 352–360 (2016).
de Boer, A. G. et al. Quality of life after transhiatal compared with extended transthoracic resection for adenocarcinoma of the esophagus. J. Clin. Oncol. 22, 4202–4208 (2004).
Luketich, J. D. et al. Minimally invasive esophagectomy: results of a prospective phase II multicenter trial — the eastern cooperative oncology group (E2202) study. Ann. Surg. 261, 702–707 (2015).
Dantoc, M. M., Cox, M. R. & Eslick, G. D. Does minimally invasive esophagectomy (MIE) provide for comparable oncologic outcomes to open techniques? A systematic review. J. Gastrointest. Surg. 16, 486–494 (2012).
Biere, S. S. et al. Minimally invasive versus open oesophagectomy for patients with oesophageal cancer: a multicentre, open-label, randomised controlled trial. Lancet 379, 1887–1892 (2012).
Maas, K. W. et al. Quality of life and late complications after minimally invasive compared to open esophagectomy: results of a randomized trial. World J. Surg. 39, 1986–1993 (2015).
Rizk, N. P. et al. Optimum lymphadenectomy for esophageal cancer. Ann. Surg. 251, 46–50 (2010).
Lagergren, J. et al. Extent of lymphadenectomy and prognosis after esophageal cancer surgery. JAMA Surg. 151, 32–39 (2016).
van der Schaaf, M., Johar, A., Wijnhoven, B., Lagergren, P. & Lagergren, J. Extent of lymph node removal during esophageal cancer surgery and survival. J. Natl Cancer Inst. 107, djv043 (2015).
Koen Talsma, A. et al. Lymph node retrieval during esophagectomy with and without neoadjuvant chemoradiotherapy: prognostic and therapeutic impact on survival. Ann. Surg. 260, 786–792; discussion 792–783 (2014).
Filip, B. et al. Minimally invasive surgery for esophageal cancer: a review on sentinel node concept. Surg. Endosc. 28, 1238–1249 (2014).
Derogar, M., Sadr-Azodi, O., Johar, A., Lagergren, P. & Lagergren, J. Hospital and surgeon volume in relation to survival after esophageal cancer surgery in a population-based study. J. Clin. Oncol. 31, 551–557 (2013). A study that assesses surgeon and hospital volume in relation to long-term prognosis, and that is important because it adjusts for all relevant factors, including mutual adjustment for surgeon and hospital volume.
Brusselaers, N., Mattsson, F. & Lagergren, J. Hospital and surgeon volume in relation to long-term survival after oesophagectomy: systematic review and meta-analysis. Gut 63, 1393–1400 (2014).
Mamidanna, R. et al. Surgeon volume and cancer esophagectomy, gastrectomy, and pancreatectomy: a population-based study in England. Ann. Surg. 263, 727–732 (2016).
Tapias, L. F. & Morse, C. R. Minimally invasive Ivor Lewis esophagectomy: description of a learning curve. J. Am. Coll. Surg. 218, 1130–1140 (2014).
Markar, S. R., Mackenzie, H., Lagergren, P., Hanna, G. B. & Lagergren, J. Surgical proficiency gain and survival after esophagectomy for cancer. J. Clin. Oncol. 34, 1528–1536 (2016). A study that reveals a long learning curve for surgeons performing oesophagectomies.
Markar, S. R., Mackenzie, H., Lagergren, P. & Lagergren, J. Surgeon age in relation to prognosis after esophageal cancer resection. Ann. Surg.http://dx.doi.org/10.1097/SLA.0000000000002260 (2017).
Lagergren, J., Mattsson, F. & Lagergren, P. Weekday of esophageal cancer surgery and its relation to prognosis. Ann. Surg. 263, 1133–1137 (2016).
Nienhueser, H. et al. Surgery of gastric cancer and esophageal cancer: does age matter? J. Surg. Oncol. 112, 387–395 (2015).
Alibakhshi, A. et al. The effect of age on the outcome of esophageal cancer surgery. Ann. Thorac Med. 4, 71–74 (2009).
Paulus, E. et al. Esophagectomy for cancer in octogenarians: should we do it? Langenbecks Arch. Surg. 402, 539–545 (2017).
Liu, J. H. et al. Disparities in the utilization of high-volume hospitals for complex surgery. JAMA 296, 1973–1980 (2006).
Revels, S. L., Morris, A. M., Reddy, R. M., Akateh, C. & Wong, S. L. Racial disparities in esophageal cancer outcomes. Ann. Surg. Oncol. 20, 1136–1141 (2013).
Zhang, S. S. et al. The impact of body mass index on complication and survival in resected oesophageal cancer: a clinical-based cohort and meta-analysis. Br. J. Cancer 109, 2894–2903 (2013).
Kayani, B. et al. Does obesity affect outcomes in patients undergoing esophagectomy for cancer? A meta-analysis. World J. Surg. 36, 1785–1795 (2012).
Zheng, Y. et al. Smoking affects treatment outcome in patients with resected esophageal squamous cell carcinoma who received chemotherapy. PLoS ONE 10, e0123246 (2015).
Huang, Q. et al. Impact of alcohol consumption on survival in patients with esophageal carcinoma: a large cohort with long-term follow-up. Cancer Sci. 105, 1638–1646 (2014).
Brusselaers, N., Mattsson, F., Lindblad, M. & Lagergren, J. Association between education level and prognosis after esophageal cancer surgery: a Swedish population-based cohort study. PLoS ONE 10, e0121928 (2015).
Rice, T. W., Rusch, V. W., Ishwaran, H. & Blackstone, E. H. Cancer of the esophagus and esophagogastric junction: data-driven staging for the seventh edition of the American Joint Committee on Cancer/International Union Against Cancer Cancer Staging Manuals. Cancer 116, 3763–3773 (2010).
Sunde, B. et al. Relief of dysphagia during neoadjuvant treatment for cancer of the esophagus or gastroesophageal junction. Dis. Esophagus 29, 442–447 (2016).
Stahl, M. et al. Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J. Clin. Oncol. 23, 2310–2317 (2005).
Bedenne, L. et al. Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J. Clin. Oncol. 25, 1160–1168 (2007).
Medical Research Council Oesophageal Cancer Working Group. Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet 359, 1727–1733 (2002).
Allum, W. H., Stenning, S. P., Bancewicz, J., Clark, P. I. & Langley, R. E. Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J. Clin. Oncol. 27, 5062–5067 (2009). A paper that reports the long-term results of a trial that defined neoadjuvant chemotherapy as a standard of care for resectable oesophageal cancer.
Alderson, D. et al. Neoadjuvant chemotherapy for resectable oesophageal and junctional adenocarcinoma: results from the UK Medical Research Council randomised OEO5 trial (ISRCTN 01852072). J. Clin. Oncol. 33, 4002 (2015).
Cunningham, D. et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N. Engl. J. Med. 355, 11–20 (2006).
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. 29, 1715–1721 (2011).
Al-Batran, S.-E. et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 17, 1697–1708 (2016).
Al-Batran, S., Homann, N., Schmalenberg, H. & Kopp, H. Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): a multicenter, randomized phase 3 trial. J. Clin. Oncol. 35, 4004 (2017).
Sjoquist, K. M. et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 12, 681–692 (2011).
Mariette, C. et al. Surgery alone versus chemoradiotherapy followed by surgery for stage I and II esophageal cancer: final analysis of randomized controlled phase III trial FFCD 9901. J. Clin. Oncol. 32, 2416–2422 (2014).
van Hagen, P. et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N. Engl. J. Med. 366, 2074–2084 (2012). A randomized trial that defines neoadjuvant chemoradiotherapy as a standard of care for resectable oesophageal cancer.
Walsh, T. N. et al. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N. Engl. J. Med. 335, 462–467 (1996).
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. 16, 1090–1098 (2015).
Klevebro, F. et al. A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction. Ann. Oncol. 27, 660–667 (2016).
Yoon, D. H. et al. Randomized phase 2 trial of S1 and oxaliplatin-based chemoradiotherapy with or without induction chemotherapy for esophageal cancer. Int. J. Radi. Oncol. Biol. Phys. 91, 489–496 (2015).
Ajani, J. A. et al. A phase II randomized trial of induction chemotherapy versus no induction chemotherapy followed by preoperative chemoradiation in patients with esophageal cancer. Ann. Oncol. 24, 2844–2849 (2013).
Minsky, B. D. 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. 20, 1167–1174 (2002).
Markar, S. et al. Salvage surgery after chemoradiotherapy in the management of esophageal cancer: is it a viable therapeutic option? J. Clin. Oncol. 33, 3866–3873 (2015).
Marks, J. L. et al. Salvage esophagectomy after failed definitive chemoradiation for esophageal adenocarcinoma. Ann. Thorac. Surg. 94, 1126–1132; discussion 1132–1123 (2012).
Swisher, S. G., Marks, J. & Rice, D. Salvage esophagectomy for persistent or recurrent disease after definitive chemoradiation. Ann. Cardiothorac Surg. 6, 144–151 (2017).
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. 15, 305–314 (2014).
Schmid, E. U. et al. The value of radiotherapy or chemotherapy after intubation for advanced esophageal carcinoma — a prospective randomized trial. Radiother. Oncol. 28, 27–30 (1993).
Levard, H. et al. 5-Fluorouracil and cisplatin as palliative treatment of advanced oesophageal squamous cell carcinoma. A multicentre randomised controlled trial. Eur. J. Surg. 164, 849–857 (1998).
Smyth, E. C. et al. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 27, v38–v49 (2016).
Guimbaud, R. et al. Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Cooperateur Multidisciplinaire en Oncologie) study. J. Clin. Oncol. 32, 3520–3526 (2014).
Dank, M. et al. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann. Oncol. 19, 1450–1457 (2008).
Cunningham, D. et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N. Engl. J. Med. 358, 36–46 (2008).
Koizumi, W. et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 9, 215–221 (2008).
Ajani, J. A. et al. Phase I pharmacokinetic study of S-1 plus cisplatin in patients with advanced gastric carcinoma. J. Clin. Oncol. 23, 6957–6965 (2005).
Thuss-Patience, P. C. et al. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer — a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur. J. Cancer 47, 2306–2314 (2011).
Kang, J. H. et al. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J. Clin. Oncol. 30, 1513–1518 (2012).
Ford, H. E. et al. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 15, 78–86 (2014).
Wagner, A. D. et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst. Rev. 3, CD004064 (2010).
Van Cutsem, E. et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 study group. J. Clin. Oncol. 24, 4991–4997 (2006).
Shah, M. A. et al. Randomized multicenter phase II study of modified docetaxel, cisplatin, and fluorouracil (DCF) versus DCF plus growth factor support in patients with metastatic gastric adenocarcinoma: a study of the US Gastric Cancer Consortium. J. Clin. Oncol. 33, 3874–3879 (2015).
Van Cutsem, E. et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer 18, 476–484 (2015).
Bang, Y. J. et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376, 687–697 (2010).
Fuchs, C. S. et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 383, 31–39 (2014).
Wilke, H. et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 15, 1224–1235 (2014).
Lagergren, J. & Lagergren, P. Oesophageal cancer. BMJ 341, c6280 (2010).
Blazeby, J. M. et al. Core information set for oesophageal cancer surgery. Br. J. Surg. 102, 936–943 (2015).
McNair, A. G. et al. What surgeons tell patients and what patients want to know before major cancer surgery: a qualitative study. BMC Cancer 16, 258 (2016).
Le Roy, B. et al. Effect of prehabilitation in gastro-oesophageal adenocarcinoma: study protocol of a multicentric, randomised, control trial-the PREHAB study. BMJ Open 6, e012876 (2016). A paper that describes the protocol of an important trial that aimed to prepare patients before surgery to recover more quickly during their rehabilitation.
Correia, M. I. & Waitzberg, D. L. The impact of malnutrition on morbidity, mortality, length of hospital stay and costs evaluated through a multivariate model analysis. Clin. Nutr. 22, 235–239 (2003).
Baiocchi, G. L. et al. Follow-up after gastrectomy for cancer: the Charter Scaligero Consensus Conference. Gastric Cancer 19, 15–20 (2016).
Blazeby, J. M., Sanford, E., Falk, S. J., Alderson, D. & Donovan, J. L. Health-related quality of life during neoadjuvant treatment and surgery for localized esophageal carcinoma. Cancer 103, 1791–1799 (2005).
Rees, J. et al. Patient-reported outcomes during and after definitive chemoradiotherapy for oesophageal cancer. Br. J. Cancer 113, 603–610 (2015).
Rutegard, M. et al. Population-based study of surgical factors in relation to health-related quality of life after oesophageal cancer resection. Br. J. Surg. 95, 592–601 (2008).
Derogar, M., Orsini, N., Sadr-Azodi, O. & Lagergren, P. Influence of major postoperative complications on health-related quality of life among long-term survivors of esophageal cancer surgery. J. Clin. Oncol. 30, 1615–1619 (2012). A well-designed, population-based, prospective and nationwide study with short-term and long-term data on health-related QOL.
Wainwright, D., Donovan, J. L., Kavadas, V., Cramer, H. & Blazeby, J. M. Remapping the body: learning to eat again after surgery for esophageal cancer. Qual. Health Res. 17, 759–771 (2007).
Amdal, C. D., Jacobsen, A. B., Guren, M. G. & Bjordal, K. Patient-reported outcomes evaluating palliative radiotherapy and chemotherapy in patients with oesophageal cancer: a systematic review. Acta Oncol. 52, 679–690 (2013).
Verschuur, E. M. et al. Nurse-led follow-up of patients after oesophageal or gastric cardia cancer surgery: a randomised trial. Br. J. Cancer 100, 70–76 (2009).
Polinder, S., Verschuur, E. M., Siersema, P. D., Kuipers, E. J. & Steyerberg, E. W. Cost comparison study of two different follow-up protocols after surgery for oesophageal cancer. Eur. J. Cancer 45, 2110–2115 (2009).
Lewis, R. et al. Nurse-led versus conventional physician-led follow-up for patients with cancer: systematic review. J. Adv. Nurs. 65, 706–723 (2009).
Kumar, S. et al. Mass spectrometric analysis of exhaled breath for the identification of volatile organic compound biomarkers in esophageal and gastric adenocarcinoma. Ann. Surg. 262, 981–990 (2015).
Dutton, S. J. et al. Gefitinib for oesophageal cancer progressing after chemotherapy (COG): a phase 3, multicentre, double-blind, placebo-controlled randomised trial. Lancet Oncol. 15, 894–904 (2014).
Ohtsu, A. et al. Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 study. J. Clin. Oncol. 31, 3935–3943 (2013).
Ohtsu, A. et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J. Clin. Oncol. 29, 3968–3976 (2011).
Bang, Y.-J. et al. A randomized, open-label phase II study of AZD4547 (AZD) versus paclitaxel (P) in previously treated patients with advanced gastric cancer (AGC) with fibroblast growth factor receptor 2 (FGFR2) polysomy or gene amplification (amp): SHINE study. J. Clin. Oncol. 33, 4014 (2015).
Ge, X. et al. Clinical significance of assessing Her2/neu expression in gastric cancer with dual tumor tissue paraffin blocks. Hum. Pathol. 46, 850–857 (2015).
Yoon, H. H. et al. Adverse prognostic impact of intratumor heterogeneous HER2 gene amplification in patients with esophageal adenocarcinoma. J. Clin. Oncol. 30, 3932–3938 (2012).
Gomez-Martin, C. et al. Level of HER2 gene amplification predicts response and overall survival in HER2-positive advanced gastric cancer treated with trastuzumab. J. Clin. Oncol. 31, 4445–4452 (2013).
Petty, R. D. et al. Epidermal growth factor receptor copy number gain (EGFR CNG) and response to gefitinib in esophageal cancer (EC): results of a biomarker analysis of a phase III trial of gefitinib versus placebo (TRANS-COG). J. Clin. Oncol. 32, 4016 (2014).
Pearson, A. et al. High-level clonal FGFR amplification and response to FGFR inhibition in a translational clinical trial. Cancer Discov. 6, 838–851 (2016).
Hortobagyi, G. N. et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N. Engl. J. Med. 375, 1738–1748 (2016).
Ismail, A. et al. Early G1 cyclin-dependent kinases as prognostic markers and potential therapeutic targets in esophageal adenocarcinoma. Clin. Cancer Res. 17, 4513–4522 (2011).
Bang, Y. et al. Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy: phase III GOLD study. Ann. Oncol. 27, 1–36 (2016).
Cafferkey, C. et al. Genomic loss of heterozygosity (LOH) and survival in patients (pts) treated with epirubicin, oxaliplatin, capecitabine (EOC) ± panitumumab (P) in the REAL3 trial. Ann. Oncol. 27, 649P (2016).
Swisher, E. M. et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 18, 75–87 (2017).
Van Allen, E. M. et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 350, 207–211 (2015).
Doi, T. et al. Updated results for the advanced esophageal carcinoma cohort of the phase 1b KEYNOTE-028 study of pembrolizumab. J. Clin. Oncol. 34, 4046 (2016).
Kudo, T. et al. Nivolumab treatment for oesophageal squamous-cell carcinoma: an open-label, multicentre, phase 2 trial. Lancet Oncol. 18, 631–639 (2017).
Janjigian, Y. Y. et al. CheckMate-032: phase I/II, open-label study of safety and activity of nivolumab (nivo) alone or with ipilimumab (ipi) in advanced and metastatic (A/M) gastric cancer (GC). J. Clin. Oncol. 34, 4010 (2016).
Kang, Y. Nivolumab (ONO-4538/BMS-936558) as salvage treatment after 2nd or later line chemotherapy for advanced gastric or gastro-esophageal junction cancer (AGC): a double-blinded, randomized phase III trial. J. Clin. Oncol. 35, 2 (2017).
Rice, T. W., Ishwaran, H., Ferguson, M. K., Blackstone, E. H. & Goldstraw, P. Cancer of the esophagus and esophagogastric junction: an eighth edition staging primer. J. Thorac. Oncol. 12, 36–42 (2017).
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. 26, 1086–1092 (2008).
Herskovic, A. et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N. Engl. J. Med. 326, 1593–1598 (1992).
E.C.S. and D.C. acknowledge funding support from the Royal Marsden Institute of Cancer Research National Institute of Health Research Biomedical Research Centre, London, UK.
E.C.S. declares honoraria for an advisory role from Five Prime Therapeutics and Bristol-Myers Squibb. D.C. declares institutional research funding from Amgen, AstraZeneca, Bayer, Celgene, MedImmune, Merck Serono, Merrimack and Sanofi. F.L. has received research support from GlaxoSmithKline and Fresenius Biotech; lecture and advisory honoraria from Amgen, Biontech, Bristol-Myers Squibb, Eli Lilly, Ganymed, Merck Serono, MSD, Nordic and Roche; and travel support from Amgen, Bayer, Roche and Taiho. M.A.S. declares institutional research funding from Genentech, Sanofi and Lilly. J.L., P.L. and R.C.F. are named on patents related to the Cytosponge and associated assays, which have been licensed by the Medical Research Council to Covidien (now Medtronic).
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Smyth, E., Lagergren, J., Fitzgerald, R. et al. Oesophageal cancer. Nat Rev Dis Primers 3, 17048 (2017). https://doi.org/10.1038/nrdp.2017.48
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