Towards Personalized Treatment Strategies for Esophageal Adenocarcinoma; A Review on the Molecular Characterization of Esophageal Adenocarcinoma and Current Research Efforts on Individualized Curative Treatment Regimens
Abstract
Simple Summary
Abstract
1. Introduction
2. Methods
3. Results
3.1. Transcriptomic Analyses to Identify Distinct Subtypes of EAC
3.2. Active Surveillance Instead of Immediate Surgical Resection
Trial | Population | Intervention | Comparison | Outcome |
---|---|---|---|---|
SANO trial [52] | 224 patients with EAC and ESCC and complete clinical response to nCRT | nCRT according to CROSS and active surveillance (CRE regimen ^) and surgery when needed | nCRT according to CROSS and standard esophagectomy | * Overall survival * Clinically complete response at 4–6 weeks after CROSS (bite-on-bite biopsies) * Clinically complete response at 10–14 weeks after CROSS (CRE-II regimen ^) |
Esostrate trial [54] | 300 patients with EAC and ESCC and complete clinical response to standard of care first-line CRT regimens | Standard of care first-line CRT regimens (not specified) and surveillance and salvage surgery | Standard of care first-line CRT regimens and standard surgical resection | * Survival |
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Eyck, B.M.; van Lanschot, J.J.B.; Hulshof, M.C.C.M.; van der Wilk, B.J.; Shapiro, J.; van Hagen, P.; van Berge Henegouwen, M.I.; Wijnhoven, B.P.L.; van Laarhoven, H.W.M.; Nieuwenhuijzen, G.A.P.; et al. Ten-year outcome of neoadjuvant chemoradiotherapy plus surgery for esophageal cancer: The randomized controlled CROSS trial. J. Clin. Oncol. 2021, 39, 1995–2004. [Google Scholar] [CrossRef] [PubMed]
- Dijksterhuis, W.P.M.; Verhoeven, R.H.A.; Slingerland, M.; Haj Mohammad, N.; de Vos-Geelen, J.; Beerepoot, L.V.; van Voorthuizen, T.; Creemers, G.J.; van Oijen, M.G.H.; van Laarhoven, H.W.M. Heterogeneity of first-line palliative systemic treatment in synchronous metastatic esophagogastric cancer patients: A real-world evidence study. Int. J. Cancer 2020, 146, 1889–1901. [Google Scholar] [CrossRef] [PubMed]
- Rubenstein, J.H.; Shaheen, N.J. Epidemiology, diagnosis, and management of esophageal adenocarcinoma. Gastroenterology 2015, 149, 302–317. [Google Scholar] [CrossRef] [PubMed]
- Berry, M.F. Esophageal cancer: Staging system and guidelines for staging and treatment. J. Thorac. Dis. 2014, 6, S289–S297. [Google Scholar] [CrossRef] [PubMed]
- van Hagen, P.; Hulshof, M.C.; van Lanschot, J.J.; Steyerberg, E.W.; van Berge Henegouwen, M.I.; Wijnhoven, B.P.; Richel, D.J.; Nieuwenhuijzen, G.A.; Hospers, G.A.; Bonenkamp, J.J.; et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N. Engl. J. Med. 2012, 366, 2074–2084. [Google Scholar] [CrossRef] [PubMed]
- Makovec, T. Cisplatin and beyond: Molecular mechanisms of action and drug resistance development in cancer chemotherapy. Radiol. Oncol. 2019, 53, 148–158. [Google Scholar] [CrossRef]
- Ojima, I.; Lichtenthal, B.; Lee, S.; Wang, C.; Wang, X. Taxane anticancer agents: A patent perspective. Expert Opin. Ther. Pat. 2016, 26, 1–20. [Google Scholar] [CrossRef]
- Al-Batran, S.E.; Homann, N.; Pauligk, C.; Goetze, T.O.; Meiler, J.; Kasper, S.; Kopp, H.G.; Mayer, F.; Haag, G.M.; Luley, K.; et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): A randomised, phase 2/3 trial. Lancet 2019, 393, 1948–1957. [Google Scholar] [CrossRef]
- Al-Batran, S.E.; Hofheinz, R.D.; Pauligk, C.; Kopp, H.G.; Haag, G.M.; Luley, K.B.; Meiler, J.; Homann, N.; Lorenzen, S.; Schmalenberg, H.; 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. 2016, 17, 1697–1708. [Google Scholar] [CrossRef]
- Alvarez, P.; Marchal, J.A.; Boulaiz, H.; Carrillo, E.; Velez, C.; Rodriguez-Serrano, F.; Melguizo, C.; Prados, J.; Madeddu, R.; Aranega, A. 5-Fluorouracil derivatives: A patent review. Expert Opin. Ther. Pat. 2012, 22, 107–123. [Google Scholar] [CrossRef]
- Peters, G.J.; van der Wilt, C.L.; van Groeningen, C.J.; Smid, K.; Meijer, S.; Pinedo, H.M. Thymidylate synthase inhibition after administration of fluorouracil with or without leucovorin in colon cancer patients: Implications for treatment with fluorouracil. J. Clin. Oncol. 1994, 12, 2035–2042. [Google Scholar] [CrossRef]
- Cunningham, D.; Allum, W.H.; Stenning, S.P.; Thompson, J.N.; Van de Velde, C.J.; Nicolson, M.; Scarffe, J.H.; Lofts, F.J.; Falk, S.J.; Iveson, T.J.; et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N. Engl. J. Med. 2006, 355, 11–20. [Google Scholar] [CrossRef]
- Plosker, G.L.; Faulds, D. Epirubicin. Drugs 1993, 45, 788–856. [Google Scholar] [CrossRef]
- Courrech Staal, E.F.; Aleman, B.M.; Boot, H.; van Velthuysen, M.L.; van Tinteren, H.; van Sandick, J.W. Systematic review of the benefits and risks of neoadjuvant chemoradiation for oesophageal cancer. Br. J. Surg. 2010, 97, 1482–1496. [Google Scholar] [CrossRef]
- Mandard, A.M.; Dalibard, F.; Mandard, J.C.; Marnay, J.; Henry-Amar, M.; Petiot, J.F.; Roussel, A.; Jacob, J.H.; Segol, P.; Samama, G.; et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer 1994, 73, 2680–2686. [Google Scholar] [CrossRef]
- Karamitopoulou, E.; Thies, S.; Zlobec, I.; Ott, K.; Feith, M.; Slotta-Huspenina, J.; Lordick, F.; Becker, K.; Langer, R. Assessment of tumor regression of esophageal adenocarcinomas after neoadjuvant chemotherapy: Comparison of 2 commonly used scoring approaches. Am. J. Surg. Pathol. 2014, 38, 1551–1556. [Google Scholar] [CrossRef] [PubMed]
- Metzger, R.; Heukamp, L.; Drebber, U.; Bollschweiler, E.; Zander, T.; Hoelscher, A.H.; Warnecke-Eberz, U. CUL2 and STK11 as novel response-predictive genes for neoadjuvant radiochemotherapy in esophageal cancer. Pharmacogenomics 2010, 11, 1105–1113. [Google Scholar] [CrossRef] [PubMed]
- Brabender, J.; Vallböhmer, D.; Grimminger, P.; Hoffmann, A.C.; Ling, F.; Lurje, G.; Bollschweiler, E.; Schneider, P.M.; Hölscher, A.H.; Metzger, R. ERCC1 RNA expression in peripheral blood predicts minor histopathological response to neoadjuvant radio-chemotherapy in patients with locally advanced cancer of the esophagus. J. Gastrointest. Surg. 2008, 12, 1815–1821. [Google Scholar] [CrossRef]
- Ling, F.C.; Leimbach, N.; Baldus, S.E.; Buechel, S.; Neiss, S.; Brabender, J.; Drebber, U.; Dienes, H.P.; Mueller, R.P.; Hoelscher, A.H.; et al. HIF-1alpha mRNA is not associated with histopathological regression following neoadjuvant chemoradiation in esophageal cancer. Anticancer. Res. 2006, 26, 4505–4509. [Google Scholar] [PubMed]
- Xi, H.; Baldus, S.E.; Warnecke-Eberz, U.; Brabender, J.; Neiss, S.; Metzger, R.; Ling, F.C.; Dienes, H.P.; Bollschweiler, E.; Moenig, S.; et al. High cyclooxygenase-2 expression following neoadjuvant radiochemotherapy is associated with minor histopathologic response and poor prognosis in esophageal cancer. Clin. Cancer Res. 2005, 11, 8341–8347. [Google Scholar] [CrossRef] [PubMed]
- Warnecke-Eberz, U.; Metzger, R.; Miyazono, F.; Baldus, S.E.; Neiss, S.; Brabender, J.; Schaefer, H.; Doerfler, W.; Bollschweiler, E.; Dienes, H.P.; et al. High specificity of quantitative excision repair cross-complementing 1 messenger RNA expression for prediction of minor histopathological response to neoadjuvant radiochemotherapy in esophageal cancer. Clin. Cancer Res. 2004, 10, 3794–3799. [Google Scholar] [CrossRef][Green Version]
- Bollschweiler, E.; Hölscher, A.H.; Herbold, T.; Metzger, R.; Alakus, H.; Schmidt, H.; Drebber, U.; Warnecke-Eberz, U. Molecular markers for the prediction of minor response to neoadjuvant chemoradiation in esophageal cancer: Results of the prospective cologne esophageal response prediction (CERP) study. Ann. Surg. 2016, 264, 839–846. [Google Scholar] [CrossRef]
- Grimminger, P.; Vallböhmer, D.; Hoffmann, A.; Schulte, C.; Bollschweiler, E.; Schneider, P.M.; Hölscher, A.H.; Metzger, R.; Brabender, J. Quantitative analysis of survivin RNA expression in blood as a non-invasive predictor of response to neoadjuvant radiochemotherapy in esophageal cancer. J. Surg. Oncol. 2009, 100, 447–451. [Google Scholar] [CrossRef] [PubMed]
- Miyazono, F.; Metzger, R.; Warnecke-Eberz, U.; Baldus, S.E.; Brabender, J.; Bollschweiler, E.; Doerfler, W.; Mueller, R.P.; Dienes, H.P.; Aikou, T.; et al. Quantitative c-erbB-2 but not c-erbB-1 mRNA expression is a promising marker to predict minor histopathologic response to neoadjuvant radiochemotherapy in oesophageal cancer. Br. J. Cancer 2004, 91, 666–672. [Google Scholar] [CrossRef]
- Warnecke-Eberz, U.; Metzger, R.; Bollschweiler, E.; Baldus, S.E.; Mueller, R.P.; Dienes, H.P.; Hoelscher, A.H.; Schneider, P.M. TaqMan low-density arrays and analysis by artificial neuronal networks predict response to neoadjuvant chemoradiation in esophageal cancer. Pharmacogenomics 2010, 11, 55–64. [Google Scholar] [CrossRef] [PubMed]
- Asleh, K.; Brauer, H.A.; Sullivan, A.; Lauttia, S.; Lindman, H.; Nielsen, T.O.; Joensuu, H.; Thompson, E.A.; Chumsri, S. Predictive biomarkers for adjuvant capecitabine benefit in early-stage triple-negative breast cancer in the FinXX clinical trial. Clin. Cancer Res. 2020, 26, 2603–2614. [Google Scholar] [CrossRef] [PubMed]
- Reis, P.P.; Tokar, T.; Goswami, R.S.; Xuan, Y.; Sukhai, M.; Seneda, A.L.; Móz, L.E.S.; Perez-Ordonez, B.; Simpson, C.; Goldstein, D.; et al. A 4-gene signature from histologically normal surgical margins predicts local recurrence in patients with oral carcinoma: Clinical validation. Sci. Rep. 2020, 10, 1713. [Google Scholar] [CrossRef] [PubMed]
- Soran, A.; Tane, K.; Sezgin, E.; Bhargava, R. The correlation of magee equations(TM) and oncotype DX(®) recurrence score from core needle biopsy tissues in predicting response to neoadjuvant chemotherapy in ER+ and HER2-breast cancer. Eur. J. Breast Health 2020, 16, 117–123. [Google Scholar] [CrossRef]
- Jahn, S.W.; Bösl, A.; Tsybrovskyy, O.; Gruber-Rossipal, C.; Helfgott, R.; Fitzal, F.; Knauer, M.; Balic, M.; Jasarevic, Z.; Offner, F.; et al. Clinically high-risk breast cancer displays markedly discordant molecular risk predictions between the MammaPrint and EndoPredict tests. Br. J. Cancer 2020, 122, 1744–1746. [Google Scholar] [CrossRef]
- Chiam, K.; Mayne, G.C.; Watson, D.I.; Woodman, R.J.; Bright, T.F.; Michael, M.Z.; Karapetis, C.S.; Irvine, T.; Phillips, W.A.; Hummel, R.; et al. Identification of microRNA biomarkers of response to neoadjuvant chemoradiotherapy in esophageal adenocarcinoma using next generation sequencing. Ann. Surg. Oncol. 2018, 25, 2731–2738. [Google Scholar] [CrossRef]
- Kim, J.; Bowlby, R.; Mungall, A.J.; Robertson, A.G.; Odze, R.D.; Cherniack, A.D.; Shih, J.; Pedamallu, C.S.; Cibulskis, C.; Dunford, A.; et al. Integrated genomic characterization of oesophageal carcinoma. Nature 2017, 541, 169–175. [Google Scholar] [CrossRef]
- Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014, 513, 202–209. [Google Scholar] [CrossRef] [PubMed]
- Bornschein, J.; Wernisch, L.; Secrier, M.; Miremadi, A.; Perner, J.; MacRae, S.; O’Donovan, M.; Newton, R.; Menon, S.; Bower, L.; et al. Transcriptomic profiling reveals three molecular phenotypes of adenocarcinoma at the gastroesophageal junction. Int. J. Cancer 2019, 145, 3389–3401. [Google Scholar] [CrossRef] [PubMed]
- Kim, S.M.; Park, Y.Y.; Park, E.S.; Cho, J.Y.; Izzo, J.G.; Zhang, D.; Kim, S.B.; Lee, J.H.; Bhutani, M.S.; Swisher, S.G.; et al. Prognostic biomarkers for esophageal adenocarcinoma identified by analysis of tumor transcriptome. PLoS ONE 2010, 5, e15074. [Google Scholar] [CrossRef] [PubMed]
- Ohashi, T.; Idogawa, M.; Sasaki, Y.; Suzuki, H.; Tokino, T. AKR1B10, a transcriptional target of p53, is downregulated in colorectal cancers associated with poor prognosis. Mol. Cancer Res. 2013, 11, 1554–1563. [Google Scholar] [CrossRef] [PubMed]
- Ingenuity. Available online: https://targetexplorer.ingenuity.com/gene/EG/11166#!/api/rest/v1/client/searchPathwayNodes?pathwayId=ING:cim&focusNodeId=EG/11166&rows=0&facetLimit=5000&responseType=default (accessed on 28 September 2021).
- Ingenuity. Available online: https://targetexplorer.ingenuity.com/gene/EG/27122#!/api/rest/v1/client/searchPathwayNodes?pathwayId=ING:4ctnm&focusNodeId=EG/27122&rows=0&facetLimit=5000&responseType=default (accessed on 28 September 2021).
- Lin, J.; Myers, A.L.; Wang, Z.; Nancarrow, D.J.; Ferrer-Torres, D.; Handlogten, A.; Leverenz, K.; Bao, J.; Thomas, D.G.; Wang, T.D.; et al. Osteopontin (OPN/SPP1) isoforms collectively enhance tumor cell invasion and dissemination in esophageal adenocarcinoma. Oncotarget 2015, 6, 22239–22257. [Google Scholar] [CrossRef]
- Stelzer, G.R.R.; Plaschkes, I.; Zimmerman, S.; Twik, M.; Fishilevich, S.; Iny Stein, T.; Nudel, R.; Lieder, I.; Mazor, Y.; Kaplan, S.; et al. GeneCards—The Human Gene Database. Available online: https://www.genecards.org/cgi-bin/carddisp.pl?gene=SPP1&keywords=SPP1 (accessed on 28 September 2021).
- Bedenne, L.; Michel, P.; Bouché, O.; Milan, C.; Mariette, C.; Conroy, T.; Pezet, D.; Roullet, B.; Seitz, J.F.; Herr, J.P.; et al. Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J. Clin. Oncol. 2007, 25, 1160–1168. [Google Scholar] [CrossRef]
- Stahl, M.; Stuschke, M.; Lehmann, N.; Meyer, H.J.; Walz, M.K.; Seeber, S.; Klump, B.; Budach, W.; Teichmann, R.; Schmitt, M.; et al. Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J. Clin. Oncol. 2005, 23, 2310–2317. [Google Scholar] [CrossRef]
- Furlong, H.; Bass, G.; Breathnach, O.; O’Neill, B.; Leen, E.; Walsh, T.N. Targeting therapy for esophageal cancer in patients aged 70 and over. J. Geriatr. Oncol. 2013, 4, 107–113. [Google Scholar] [CrossRef]
- Taketa, T.; Correa, A.M.; Suzuki, A.; Blum, M.A.; Chien, P.; Lee, J.H.; Welsh, J.; Lin, S.H.; Maru, D.M.; Erasmus, J.J.; et al. Outcome of trimodality-eligible esophagogastric cancer patients who declined surgery after preoperative chemoradiation. Oncology 2012, 83, 300–304. [Google Scholar] [CrossRef]
- Shapiro, J.; van Lanschot, J.J.B.; Hulshof, M.; van Hagen, P.; van Berge Henegouwen, M.I.; Wijnhoven, B.P.L.; van Laarhoven, H.W.M.; Nieuwenhuijzen, G.A.P.; Hospers, G.A.P.; Bonenkamp, J.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, 1090–1098. [Google Scholar] [CrossRef]
- Taketa, T.; Xiao, L.; Sudo, K.; Suzuki, A.; Wadhwa, R.; Blum, M.A.; Lee, J.H.; Weston, B.; Bhutani, M.S.; Skinner, H.; et al. Propensity-based matching between esophagogastric cancer patients who had surgery and who declined surgery after preoperative chemoradiation. Oncology 2013, 85, 95–99. [Google Scholar] [CrossRef]
- Oppedijk, V.; van der Gaast, A.; van Lanschot, J.J.; van Hagen, P.; van Os, R.; van Rij, C.M.; van der Sangen, M.J.; Beukema, J.C.; Rütten, H.; Spruit, P.H.; et al. Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials. J. Clin. Oncol. 2014, 32, 385–391. [Google Scholar] [CrossRef] [PubMed]
- Sudo, K.; Taketa, T.; Correa, A.M.; Campagna, M.C.; Wadhwa, R.; Blum, M.A.; Komaki, R.; Lee, J.H.; Bhutani, M.S.; Weston, B.; et al. Locoregional failure rate after preoperative chemoradiation of esophageal adenocarcinoma and the outcomes of salvage strategies. J. Clin. Oncol. 2013, 31, 4306–4310. [Google Scholar] [CrossRef] [PubMed]
- Versteijne, E.; van Laarhoven, H.W.; van Hooft, J.E.; van Os, R.M.; Geijsen, E.D.; van Berge Henegouwen, M.I.; Hulshof, M.C. Definitive chemoradiation for patients with inoperable and/or unresectable esophageal cancer: Locoregional recurrence pattern. Dis. Esophagus 2015, 28, 453–459. [Google Scholar] [CrossRef] [PubMed]
- Reid, T.D.; Davies, I.L.; Mason, J.; Roberts, S.A.; Crosby, T.D.; Lewis, W.G. Stage for stage comparison of recurrence patterns after definitive chemoradiotherapy or surgery for oesophageal carcinoma. Clin. Oncol. 2012, 24, 617–624. [Google Scholar] [CrossRef] [PubMed]
- Xi, M.; Xu, C.; Liao, Z.; Hofstetter, W.L.; Blum Murphy, M.; Maru, D.M.; Bhutani, M.S.; Lee, J.H.; Weston, B.; Komaki, R.; et al. The impact of histology on recurrence patterns in esophageal cancer treated with definitive chemoradiotherapy. Radiother. Oncol. 2017, 124, 318–324. [Google Scholar] [CrossRef]
- Noordman, B.J.; Spaander, M.C.W.; Valkema, R.; Wijnhoven, B.P.L.; van Berge Henegouwen, M.I.; Shapiro, J.; Biermann, K.; van der Gaast, A.; van Hillegersberg, R.; Hulshof, M.; et al. Detection of residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer (preSANO): A prospective multicentre, diagnostic cohort study. Lancet Oncol. 2018, 19, 965–974. [Google Scholar] [CrossRef]
- Eyck, B.M.; van der Wilk, B.J.; Noordman, B.J.; Wijnhoven, B.P.L.; Lagarde, S.M.; Hartgrink, H.H.; Coene, P.; Dekker, J.W.T.; Doukas, M.; van der Gaast, A.; et al. Updated protocol of the SANO trial: A stepped-wedge cluster randomised trial comparing surgery with active surveillance after neoadjuvant chemoradiotherapy for oesophageal cancer. Trials 2021, 22, 345. [Google Scholar] [CrossRef]
- Noordman, B.J.; Wijnhoven, B.P.L.; Lagarde, S.M.; Boonstra, J.J.; Coene, P.; Dekker, J.W.T.; Doukas, M.; van der Gaast, A.; Heisterkamp, J.; Kouwenhoven, E.A.; et al. Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: A stepped-wedge cluster randomised trial. BMC Cancer 2018, 18, 142. [Google Scholar] [CrossRef]
- Dijon, C.H.U. Comparison of Systematic Surgery Versus Surveillance and Rescue Surgery in Operable Oesophageal Cancer with a Complete Clinical Response to Radiochemotherapy (Esostrate). ClinicalTrials.gov Identifier: NCT02551458. Available online: https://clinicaltrials.gov/ct2/show/NCT02551458 (accessed on 26 September 2021).
- Fuchs, H.; Hölscher, A.H.; Leers, J.; Bludau, M.; Brinkmann, S.; Schröder, W.; Alakus, H.; Mönig, S.; Gutschow, C.A. Long-term quality of life after surgery for adenocarcinoma of the esophagogastric junction: Extended gastrectomy or transthoracic esophagectomy? Gastric Cancer 2016, 19, 312–317. [Google Scholar] [CrossRef] [PubMed]
- Stroes, C.I.; Schokker, S.; Creemers, A.; Molenaar, R.J.; Hulshof, M.; van der Woude, S.O.; Bennink, R.J.; Mathôt, R.A.A.; Krishnadath, K.K.; Punt, C.J.A.; et al. Phase II feasibility and biomarker study of neoadjuvant trastuzumab and pertuzumab with chemoradiotherapy for resectable human epidermal growth factor receptor 2-positive esophageal adenocarcinoma: Trap study. J. Clin. Oncol. 2020, 38, 462–471. [Google Scholar] [CrossRef]
- Creemers, A.; Ebbing, E.A.; Hooijer, G.K.J.; Stap, L.; Jibodh-Mulder, R.A.; Gisbertz, S.S.; van Berge Henegouwen, M.I.; van Montfoort, M.L.; Hulshof, M.; Krishnadath, K.K.; et al. The dynamics of HER2 status in esophageal adenocarcinoma. Oncotarget 2018, 9, 26787–26799. [Google Scholar] [CrossRef] [PubMed]
- Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest. Phase II Study of Atezolizumab + FLOT vs. FLOT Alone in Patients with Gastric Cancer and GEJ. ClinicalTrials.gov Identifier: NCT03421288. Available online: https://clinicaltrials.gov/ct2/show/NCT03421288 (accessed on 26 September 2021).
- Al-Batran, S.-E.; Pauligk, C.; Hofheinz, R.; Lorenzen, S.; Wicki, A.; Siebenhuener, A.R.; Schenk, M.; Welslau, M.; Heuer, V.; Goekkurt, E.; et al. Perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma: DANTE, a randomized, open-label phase II trial of the German Gastric Group of the AIO and the SAKK. J. Clin. Oncol. 2019, 37, TPS4142. [Google Scholar] [CrossRef]
- Herbst, R.S.; Soria, J.-C.; Kowanetz, M.; Fine, G.D.; Hamid, O.; Gordon, M.S.; Sosman, J.A.; McDermott, D.F.; Powderly, J.D.; Gettinger, S.N.; et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 2014, 515, 563–567. [Google Scholar] [CrossRef] [PubMed]
- Hoefnagel, S.J.M.; Mostafavi, N.; Timmer, M.R.; Lau, C.T.; Meijer, S.L.; Wang, K.K.; Krishnadath, K.K. A genomic biomarker-based model for cancer risk stratification of non-dysplastic Barrett’s esophagus patients after extended follow up; results from Dutch surveillance cohorts. PLoS ONE 2020, 15, e0231419. [Google Scholar] [CrossRef] [PubMed]
- Hasina, R.; Surati, M.; Kawada, I.; Arif, Q.; Carey, G.B.; Kanteti, R.; Husain, A.N.; Ferguson, M.K.; Vokes, E.E.; Villaflor, V.M.; et al. O-6-methylguanine-deoxyribonucleic acid methyltransferase methylation enhances response to temozolomide treatment in esophageal cancer. J. Carcinog. 2013, 12, 20. [Google Scholar] [CrossRef] [PubMed]
- Illumina Inc. RNA-Seq Data Comparison with Gene Expression Microarrays. A Cross-Platform Comparison of Differential Expression Analysis; Illumina Inc.: San Diego, CA, USA, 2011. [Google Scholar]
- Leek, J.T.; Scharpf, R.B.; Bravo, H.C.; Simcha, D.; Langmead, B.; Johnson, W.E.; Geman, D.; Baggerly, K.; Irizarry, R.A. Tackling the widespread and critical impact of batch effects in high-throughput data. Nat. Rev. Genet. 2010, 11, 733–739. [Google Scholar] [CrossRef] [PubMed]
- Moffitt, R.A.; Marayati, R.; Flate, E.L.; Volmar, K.E.; Loeza, S.G.H.; Hoadley, K.A.; Rashid, N.U.; Williams, L.A.; Eaton, S.C.; Chung, A.H.; et al. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat. Genet. 2015, 47, 1168–1178. [Google Scholar] [CrossRef]
- Saadi, A.; Shannon, N.B.; Lao-Sirieix, P.; O’Donovan, M.; Walker, E.; Clemons, N.J.; Hardwick, J.S.; Zhang, C.; Das, M.; Save, V.; et al. Stromal genes discriminate preinvasive from invasive disease, predict outcome, and highlight inflammatory pathways in digestive cancers. Proc. Natl. Acad. Sci. USA 2010, 107, 2177. [Google Scholar] [CrossRef]
- Avila Cobos, F.; Alquicira-Hernandez, J.; Powell, J.E.; Mestdagh, P.; De Preter, K. Benchmarking of cell type deconvolution pipelines for transcriptomics data. Nat. Commun. 2020, 11, 5650. [Google Scholar] [CrossRef] [PubMed]
Author, Country | Patient Material, Acquisition | Tumor Type | Number Included | Number for Analysis | TNM Stages | Treatment | Definition Response | RNA Profiling | Cluster Method |
---|---|---|---|---|---|---|---|---|---|
TCGA, Australia, Brazil, Canada, Germany, South-Korea, Moldova, Netherlands, Poland, Russia, Ukraine United Kingdom, United States of America, Vietnam [31] | Pretreatment, fresh frozen Frozen section side for pathology control with threshold ≥60% tumor nuclei and ≤20% necrosis | Gastro-esophageal adenocarcinomas | 90 ESCC 72 EAC/Esophageal GEJ 36 Indeterminate GEJ AC 63 Gastric GEJ AC 140 Fundus/Body AC 143 Antrum/Pylorus AC Not specified 13 | Not specified for analysis other than gastro-esophageal adenocarcinomas included | Pathological I, II, III, IV | NA | NA | RNA Integrity ≥ 7.0 Illumina HiSeq2000 PE 75 base sequencing | Integrative clustering of platform-specific clusters SuperCluster method and Clustering of Cluster assignments based on DNA methylation, Reverse-Phase Protein Array, Somatic Copy Number Alterations, messenger RNA and micro RNA cluster results |
Bornschein, United Kingdom, Germany [33] | Diagnostic endoscopy or surgical resection Chemo- and radiotherapy-naïve, snap-frozen tissue Macro- and microdissection to maintain threshold ≥70% tumor cellularity at one section by H&E and pathological review | Intestinal type EAC at GEJ (defined by Siewert classification), diffuse-type and mixed pathology excluded | 84 EAC patients | 61 after removing samples with enrichment of genes associated with squamous differentiation | Clinical I, II, III, IV | Curative and palliative intention, not specified | Overall survival | RNA with integrity number (RIN) > 7.0 Illumina HT12 version 4.0 beadchip kit | Mclust algorithm |
Kim, United States of America [34] | Diagnostic endoscopy Untreated, fresh-frozen tissue | EAC | 75 cancer samples from 64 patients | 75 samples | Clinical I, II, III, IV | Chemoradiation followed by surgery as primary treatment | Recurrence free survival | RNA quality index (>7) DNA microarray technology, Illumina BeadArray Reader | Unsupervised hierarchical clustering analysis based on Pearson correlation coefficients |
Author | Subgroups | Association Response | Differential Expressed Genes | Pathways | External Validation |
---|---|---|---|---|---|
TCGA, Australia, Brazil, Canada, Germany, South-Korea, Moldova, Netherlands, Poland, Russia, Ukraine United Kingdom, United States of America, Vietnam [31] | EACs and CIN gastric cancers jointly formed a group distinct from EBV, MSI or GS tumors | NA | NA | NA | No |
Bornschein, United Kingdom, Germany [33] | Three subgroups | Association with median overall survival (Group 1: 25.9 m vs. Group 2: 45.2 m vs. Group 3: 83.5 m; p = 0.019) | Adjusted p-value <= 0.05 Group 1 versus 3317 genes Group 3 versus 2243 genes Group 1 versus 2204 genes 82 candidate genes for discrimination between subtypes | Group 1 “Ribosome”, “Fatty Acid Metabolism”, “Oxidative Phosphorylation”, pathways involved in nucleic acid turnover Group 2 “Steroid Hormone Biosynthesis”, “Peroxisome”, “Primary Bile Acid Biosynthesis” and pathways involved in metabolic processes. Group 3 “Antigen Processing and Presentation”, “Chemokine Signaling Pathways”, “Natural Killer Cell-Mediated Cytotoxicity”, and pathways involved in immune-response | Subtypes confirmed successfully in all four cohorts, association with overall survival consistent in BELFAST and SINGAPORE cohorts. -OCCAMS RNASeq cohort with 154 EAC and GEJ adenocarcinomas -BELFAST Affymetrix cohort with 63 EAC -SINGAPORE Affymetrix cohort with 191 gastric cancers -Asian Cancer Research Group Affymetrix cohort with 300 gastric cancers |
Kim, United States of America [34] | Three subgroups | Association with recurrence free survival (worse in cluster B) | p < 0.002 and 1.5-fold differences between the groups cluster A versus B 2344 genes cluster B versus C 1489 genes 452 overlapping genes of the 2344 genes and 1489 genes, from which 10 selected for validation | Putative networks listed top network associated with over-representation of NF-kB | 10 genes tested with qRT-PCR on RNA from FFPE in 52 EAC SPARC and SPP1 associated with poor overall survival |
Author | Retrospective or Prospective | Number Independent EAC Cases | Quality Assessment of RNA | Tumor Percentage | Independent Cohort Validation | Overall Recommendation Level (+, +/−, −) |
---|---|---|---|---|---|---|
TCGA, Australia, Brazil, Canada, Germany, South-Korea, Moldova, Netherlands, Poland, Russia, Ukraine United Kingdom, United States of America, Vietnam [31] | Retrospective | 72 | RNA Integrity ≥ 7.0 | ≥60% tumor nuclei | No | − |
Bornschein, United Kingdom, Germany [33] | Retrospective | 84 | RNA integrity number (RIN) > 7.0 | ≥70% tumor cellularity | Yes | +/− |
Kim, United States of America [34] | Retrospective | 64 | RNA quality index (>7) | NA | Only for sub-selection of genes | − |
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Hoefnagel, S.J.M.; Boonstra, J.J.; Russchen, M.J.A.M.; Krishnadath, K.K. Towards Personalized Treatment Strategies for Esophageal Adenocarcinoma; A Review on the Molecular Characterization of Esophageal Adenocarcinoma and Current Research Efforts on Individualized Curative Treatment Regimens. Cancers 2021, 13, 4881. https://doi.org/10.3390/cancers13194881
Hoefnagel SJM, Boonstra JJ, Russchen MJAM, Krishnadath KK. Towards Personalized Treatment Strategies for Esophageal Adenocarcinoma; A Review on the Molecular Characterization of Esophageal Adenocarcinoma and Current Research Efforts on Individualized Curative Treatment Regimens. Cancers. 2021; 13(19):4881. https://doi.org/10.3390/cancers13194881
Chicago/Turabian StyleHoefnagel, Sanne J. M., Jurjen J. Boonstra, Marjolein J. A. M. Russchen, and Kausilia K. Krishnadath. 2021. "Towards Personalized Treatment Strategies for Esophageal Adenocarcinoma; A Review on the Molecular Characterization of Esophageal Adenocarcinoma and Current Research Efforts on Individualized Curative Treatment Regimens" Cancers 13, no. 19: 4881. https://doi.org/10.3390/cancers13194881
APA StyleHoefnagel, S. J. M., Boonstra, J. J., Russchen, M. J. A. M., & Krishnadath, K. K. (2021). Towards Personalized Treatment Strategies for Esophageal Adenocarcinoma; A Review on the Molecular Characterization of Esophageal Adenocarcinoma and Current Research Efforts on Individualized Curative Treatment Regimens. Cancers, 13(19), 4881. https://doi.org/10.3390/cancers13194881