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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 4/2024

23-12-2023 | Esophagus Resection | Thoracic Oncology

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

Authors: 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, Dominique Frechette, MD, Shelly Sud, MD, Petr Kavan, MD, Albert Moghrabi, MD, Martin Champagne, MD, Frederic Lemay, MD, Richard Dalfen, MD, Shireen Sirhan, MD, Jamil Asselah, MD, Thierry Alcindor, MD, Lorenzo Ferri, MD, PhD

Published in: Annals of Surgical Oncology | Issue 4/2024

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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.
Literature
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRef
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRef
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
16.
Giommoni E, Lavacchi D, Tirino G, et al. Results of the observational prospective RealFLOT study. BMC Cancer. 2021;21:1–11.CrossRef
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
19.
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.CrossRef
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRef
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
Metadata
Title
Docetaxel-Based Neoadjuvant Chemotherapy Followed by En Bloc Resection for Esophageal Adenocarcinoma: A 15-Year Retrospective Analysis from a Regional Upper Gastrointestinal Cancer Network
Authors
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
Dominique Frechette, MD
Shelly Sud, MD
Petr Kavan, MD
Albert Moghrabi, MD
Martin Champagne, MD
Frederic Lemay, MD
Richard Dalfen, MD
Shireen Sirhan, MD
Jamil Asselah, MD
Thierry Alcindor, MD
Lorenzo Ferri, MD, PhD
Publication date
23-12-2023
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 4/2024
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-023-14779-4

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