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Docetaxel-Based Neoadjuvant Chemotherapy Followed by En Bloc Resection for Esophageal Adenocarcinoma: A 15-Year Retrospective Analysis from a Regional Upper Gastrointestinal Cancer Network

  • Thoracic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Backround

Real-world, long-term survival outcomes of neoadjuvant, docetaxel-based therapy for esophageal and junctional adenocarcinoma are lacking. This study describes the long-term survival outcomes of patients with esophageal and junctional adenocarcinoma treated with neoadjuvant docetaxel-based chemotherapy and en bloc transthoracic esophagectomy.

Methods

A retrospective cohort analysis of a prospectively maintained database from a regional upper gastrointestinal cancer network in Quebec, Canada, was performed. From January 2007 to December 2021, all patients with locally advanced (cT3 and/or N1) esophageal/Siewert I/II adenocarcinoma treated with neoadjuvant DCFx3 (Docetaxel/Cisplatin/5FU) or FLOTx4 (5FU/Leucovorin/Oxaliplatin/Docetaxel) and transthoracic en bloc esophagectomy were identified. Postoperative, pathological, and survival outcomes were compared.

Results

Overall, 236 of 420 patients met the inclusion criteria. Tumor location was esophageal/Siewert I/Siewert II (118/33/85), most were cT3-4 (93.6%) and cN+ (61.0%). DCF and FLOT were used in 127 of 236 (53.8%) and 109 of 236 (46.2%). All neoadjuvant cycles were completed in 87.3% with no difference between the regimens. Operative procedures included Ivor Lewis (81.8%), left thoraco-abdominal esophagectomy (10.6%) and McKeown (7.6%) with an R0 resection in 95.3% and pathological complete response in 9.7% (DCF 12.6%/FLOT 6.4%, p = 0.111). The median lymph node yield was 32 (range 4–79), and 60.6% were ypN+. Median follow-up was longer for the DCF group (74.8 months 95% confidence interval [CI] 4–173 vs. 37.8 months 95% CI 2–119, p <0.001. Overall survival was similar between the groups (FLOT 97.3 months, 78.6–115.8 vs. DCF 92.9, 9.2–106.5, p = 0.420).

Conclusions

Neoadjuvant DCF and FLOT followed by transthoracic en bloc resection are both highly effective regimens for locally advanced esophageal adenocarcinoma with equivalent survival outcomes despite high disease load.

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References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.

    Article  PubMed  Google Scholar 

  2. Arnold M, Laversanne M, Brown LM, Devesa SS, Bray F. Predicting the future burden of esophageal cancer by histological subtype: International trends in incidence up to 2030. Am J Gastroenterol. 2017;112:1247–55.

    Article  PubMed  Google Scholar 

  3. Al-Kaabi A, Baranov NS, van der Post RS, Schoon EJ, Rosman C, van Laarhoven HWM, Verheij M, Verhoeven RHA, Siersema PD. Age-specific incidence, treatment, and survival trends in esophageal cancer: a Dutch population-based cohort study. Acta Oncol. 2022;61(5):545–52.

    Article  CAS  PubMed  Google Scholar 

  4. Akhtar-Danesh N, Shakeel S, Seow H, Akhtar-Danseh GG, Finley C. Trends in survival based on treatment modality for esophageal cancer: a population-based study. Eur J Gastroenterol Hepatol. 2019;31:1192–9.

    Article  PubMed  Google Scholar 

  5. Boonstra JJ, Kok TC, Wijnhoven BP, van Heijl M, van Berge Henegouwen MI, Ten Kate FJ, Siersema PD, Dinjens WN, van Lanschot JJ, Tilanus HW, van der Gaast A. Chemotherapy followed by surgery versus surgery alone in patients with resectable oesophageal squamous cell carcinoma: long-term results of a randomized controlled trial. BMC Cancer. 2011;19(11):181.

    Article  Google Scholar 

  6. Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Genève J, Lasser P, Rougier P. 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.

    Article  CAS  PubMed  Google Scholar 

  7. Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TPJ. A Comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996;335(7):462–7.

    Article  CAS  PubMed  Google Scholar 

  8. Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R, Kiel K, Willett C, Sugarbaker D, Mayer R. 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.

    Article  CAS  PubMed  Google Scholar 

  9. van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366:2074–84.

    Article  PubMed  Google Scholar 

  10. Ferri LE, Ades S, Alcindor T, Chasen M, Marcus V, Hickeson M, Artho G, Thirlwell MP. Perioperative docetaxel, cisplatin, and 5-fluorouracil (DCF) for locally advanced esophageal and gastric adenocarcinoma: a multicenter phase II trial. Ann Oncol. 2012;23:1512–7.

    Article  CAS  PubMed  Google Scholar 

  11. Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, von Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Weniger J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Jäger E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD. 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 radomized phase II/III trial. Lancet. 2019;393:1948–57.

    Article  PubMed  Google Scholar 

  12. Giommoni E, Lavacchi D, Tirino G, Fornaro L, Iachetta F, Pozzo C, Satolli MA, Spallanzani A, Puzzoni M, Stragliotto S, Sisani M, Formica V, Giovanardi F, Strippoli A, Prisciandaro M, Di Donato S, Pompella L, Pecora I, Romagnani A, Fancelli S, Brugia M, Pillozzi S, De Vita F, Antonuzzo L. Results of the observational prospective RealFLOT study. BMC Cancer. 2021;21:1–11.

    Article  Google Scholar 

  13. Kalff MC, van Berge Henegouwen MI, Baas PC, Bahadoer RR, Belt EJT, Brattinga B, Claassen L, Ćosović A, Crull D, Daams F, van Dalsen AD, Dekker JWT, van Det MJ, Drost M, van Duijvendijk P, Eshuis WJ, van Esser S, Gaspersz MP, Görgec B, Groenendijk RPR, Hartgrink HH, van der Harst E, Haveman JW, Heisterkamp J, van Hillegersberg R, Kelder W, Kingma BF, Koemans WJ, Kouwenhoven EA, Lagarde SM, Lecot F, van der Linden PP, Luyer MDP, Nieuwenhuijzen GAP, Olthof PB, van der Peet DL, Pierie JEN, Pierik EGJMR, Plat VD, Polat F, Rosman C, Ruurda JP, van Sandick JW, Scheer R, Slootmans CAM, Sosef MN, Sosef OV, de Steur WO, Stockmann HBAC, Stoop FJ, Voeten DM, Vugts G, Vijgen GHEJ, Weeda VB, Wiezer MJ, van Oijen MGH, Gisbertz SS. Trends in distal esophageal and gastroesophageal junction cancer care. Ann Surg. 2021;277(4):619–28.

    Article  PubMed  Google Scholar 

  14. Voeten DM, Gisbertz SS, Ruurda JP, Wilschut JA, Ferri LE, van Hillegersberg R, van Berge Henegouwen MI. Overall volume trends in esophageal cancer surgery results from the dutch upper gastrointestinal cancer audit. Ann Surg. 2021;274:449–58.

    Article  PubMed  Google Scholar 

  15. Donlon NE, Kammili A, Roopnarinesingh R, Davern M, Power R, King S, Chmelo J, Phillips AW, Donohoe CL, Ravi N, Lowery M, Mueller CL, Cools-Lartigue J, Ferri LE, Reynolds JV. FLOT-regimen chemotherapy and transthoracic en bloc resection for esophageal and junctional adenocarcinoma. Ann Surg. 2021;274(5):814–20.

    Article  PubMed  Google Scholar 

  16. Giommoni E, Lavacchi D, Tirino G, et al. Results of the observational prospective RealFLOT study. BMC Cancer. 2021;21:1–11.

    Article  Google Scholar 

  17. Stüben BO, Stuhlfelder J, Kemper M, Tachezy M, Ghadban T, Izbicki JR, Bokemeyer C, Sinn M, Karstens KF. Completion of FLOT therapy, regardless of tumor regression, significantly improves overall survival in patients with esophageal adenocarcinoma. Cancers. 2022;14:1084.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Watanabe M, Baba Y, Yoshida N, Ishimoto T, Nagai Y, Iwatsuki M, Iwagami S, Baba H. Outcomes of preoperative chemotherapy with docetaxel, cisplatin, and 5-fluorouracil followed by esophagectomy in patients with resectable node-positive esophageal cancer. Ann Surg Oncol. 2014;21:2838–44.

    Article  PubMed  Google Scholar 

  19. Kamarajah SK, Griffiths EA. Postoperative and pathological outcomes of CROSS and FLOT as neoadjuvant therapy for esophageal and junctional adenocarcinoma. Ann Surg. 2022. https://doi.org/10.1097/sla.0000000000005394.

    Article  PubMed  Google Scholar 

  20. Al-Fakeeh A, Ferri L, Mulla N, Doerksen T, Al-Ruzug I, Santos F, Alcindor T. A pilot trial of FLOT neoadjuvant chemotherapy for resectable esophagogastric junction adenocarcinoma. Med Oncol. 2016;33:1–4.

    Article  CAS  Google Scholar 

  21. Rice TW, Gress DM, Patil DT, Hofstetter WL, Kelsen DP, Blackstone EH. Cancer of the esophagus and esophagogastric junction-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(4):304–17.

    Article  PubMed  Google Scholar 

  22. Donohoe CL, O’Farrell NJ, Grant T, King S, Clarke L, Muldoon C, Reynolds JV. Classification of pathologic response to neoadjuvant therapy in esophageal and junctional cancer: Assessment of existing measures and proposal of a novel 3-point standard. Ann Surg. 2013;258:784–92.

    Article  PubMed  Google Scholar 

  23. Spicer JD, Stiles BM, Sudarshan M, Correa AM, Ferri LE, Altorki NK, Hofstetter WL. Preoperative chemoradiation therapy versus chemotherapy in patients undergoing modified en bloc esophagectomy for locally advanced esophageal adenocarcinoma: Is radiotherapy beneficial? Ann Thorac Surg. 2016;101:1262–70.

    Article  PubMed  Google Scholar 

  24. Girling DJ, Bancewicz J, Clark PI, and the Medical Research Council Oesophageal Cancer Working Groupl. Surgical resection with or without preoperative chemotherapy in oesophageal cancer: A randomised controlled trial. Lancet. 2002;359(9319):1727–33.

    Article  Google Scholar 

  25. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.

    Article  CAS  PubMed  Google Scholar 

  26. Fornaro L, Vivaldi C, Calvetti L, Cappetta A, Falcone A, Aprile G. FLOaTing toward new standards in locally advanced resectable gastroesophageal cancer. J Thorac Dis. 2019;11:5694–700.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Lorenzen S, Pauligk C, Homann N, Schmalenberg H, Jäger E, Al-Batran SE. Feasibility of perioperative chemotherapy with infusional 5-FU, leucovorin, and oxaliplatin with (FLOT) or without (FLO) docetaxel in elderly patients with locally advanced esophagogastric cancer. Br J Cancer. 2013;108:519–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA, V325 Study Group. 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 V25 study group. J Clin Oncol. 2006;24:4991–7.

    Article  PubMed  Google Scholar 

  29. Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, von Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Weniger J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Jäger E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD. 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). Lancet Oncol. 2016;17:1697–708.

    Article  CAS  PubMed  Google Scholar 

  30. Schulz C, Kullmann F, Kunzmann V, Fuchs M, Geissler M, Vehling-Kaiser U, Stauder H, Wein A, Al-Batran SE, Kubin T, Schäfer C, Stintzing S, Giessen C, Modest DP, Ridwelski K, Heinemann V. NeoFLOT: multicenter phase II study of perioperative chemotherapy in resectable adenocarcinoma of the gastroesophageal junction or gastric adenocarcinoma. Very good response predominantly in patients with intestinal type tumors. Int J Cancer. 2015;137(3):678–85.

    Article  CAS  PubMed  Google Scholar 

  31. Villanueva L, Anabalon J, Butte JM, Salman P, Panay S, Milla E, Gallardo C, Hoefler S, Charles R, Reyes F, Barajas O, Matamala L, Molina A, Portiño S, Berrios M, Caglevic C, Mahave M. Total neoadjuvant chemotherapy with FLOT scheme in resectable adenocarcinoma of the gastro-oesophageal junction or gastric adenocarcinoma: impact on pathological complete response and safety. Ecancermedicalscience. 2020;13(15):1168.

    Google Scholar 

  32. Cools-Lartigue J, Ferri L. Radiation is not a solution for suboptimal surgery. A response to the conclusions drawn from the impact of surgical approach on long-term survival in esophageal adenocarcinoma with or without neoadjuvant chemoradiotherapy study. Ann Surg. 2019;270(1):e13–4.

    Article  PubMed  Google Scholar 

  33. Li B, Chen L, Luo HL, Yi FM, Wei YP, Zhang WX. Docetaxel, cisplatin, and 5-fluorouracil compared with epirubicin, cisplatin, and 5-fluorouracil regimen for advanced gastric cancer: a systematic review and meta-analysis. World J Clin Cases. 2019;7:600–15.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Glatz T, Verst R, Kuvendjiska J, Bronsert P, Becker H, Hoeppner J, Kulemann B. Pattern of recurrence and patient survival after perioperative chemotherapy with 5-FU, leucovorin, oxaliplatin and docetaxel (FLOT) for locally advanced esophagogastric adenocarcinoma in patients treated outside clinical trials. J Clin Med. 2020;9(8):2654.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Takahashi C, Shridhar R, Huston J, Blinn P, Maramara T, Meredith K. Comparative outcomes of transthoracic versus transhiatal esophagectomy. Surgery. 2021;170(1):263–70.

    Article  PubMed  Google Scholar 

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Author notes

  1. James Tankel and Nabeel Ahmed have contributed equally to the creation of this manuscript.

Authors and Affiliations

  1. Division of Thoracic and Upper Gastrointestinal Surgery, Montreal General Hospital, McGill University Health Centre, Montreal, QC, Canada

    James Tankel MBBS, Nabeel Ahmed MD, Carmen Mueller MD, Sarah Najmeh MD, Jonathan Spicer MD, PhD, David Mulder MD, Jonathan Cool-Lartigue MD, PhD, Mathieu Rousseau MD & Lorenzo Ferri MD, PhD

  2. Department of Medical Oncology, Hopital de Gatineau, Gatineau, QC, Canada

    Dominique Frechette MD & Shelly Sud MD

  3. Deparment of Oncology, Jewish General Hospital, Montreal, QC, Canada

    Petr Kavan MD

  4. Department of Oncology, Hopital de Verdun, Montreal, QC, Canada

    Albert Moghrabi MD & Martin Champagne MD

  5. Deparmtent of Medicine, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada

    Frederic Lemay MD

  6. Division of Medical Oncology, St Mary’s Hospital Center, Montreal, QC, Canada

    Richard Dalfen MD

  7. Department of Oncology, Brome-Missisquoi-Perkins, Cowansville, QC, Canada

    Shireen Sirhan MD

  8. Division of Medical Oncology, Royal Victoria Hospital, McGill University Health Centre, Montreal, Quebec, Canada

    Jamil Asselah MD & Thierry Alcindor MD

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  1. James Tankel MBBS
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JT received a travel grant from Medtronic and receives regular consulting fees from Google. None of the other authors have conflict of interests to declare. No funding was made available for the creation of this manuscript.

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Tankel, J., Ahmed, N., Mueller, C. et al. Docetaxel-Based Neoadjuvant Chemotherapy Followed by En Bloc Resection for Esophageal Adenocarcinoma: A 15-Year Retrospective Analysis from a Regional Upper Gastrointestinal Cancer Network. Ann Surg Oncol 31, 2461–2469 (2024). https://doi.org/10.1245/s10434-023-14779-4

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