Operative Results and Perioperative Morbidity After Intensified Neoadjuvant Chemotherapy with FLOT for Gastroesophageal Adenocarcinoma Impact of Intensified Neoadjuvant Treatment.
Gastric cancer
Gastroesophageal adenocarcinoma
Intensified chemotherapy
Neoadjuvant chemotherapy
Perioperative results
Journal
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
ISSN: 1873-4626
Titre abrégé: J Gastrointest Surg
Pays: United States
ID NLM: 9706084
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
30
07
2019
accepted:
29
12
2019
pubmed:
11
2
2020
medline:
20
4
2021
entrez:
11
2
2020
Statut:
ppublish
Résumé
Perioperative treatment is the standard of care in Western Europe for locally advanced gastric cancer (GC) and adenocarcinoma of the gastroesophageal junction (GEJ). Intensified neoadjuvant treatment within the NeoFLOT trial proved to be safe and effective. Yet, the influence of such intensification with 6 cycles of FLOT in the neoadjuvant setting has not been analyzed regarding its possible impact on perioperative results. A total of 537 patients were enrolled in this study; of whom, 132 had followed a standard neoadjuvant protocol (CTx), 356 had not received any neoadjuvant treatment (NoCTx), and 49 patients had undergone an intensified chemotherapy within the NeoFLOT trial (IntCTx) with 6 cycles of FLOT (5-FU, leucovorin, oxaliplatin, docetaxel) every 2 weeks. Our results reveal no significant difference in perioperative morbidity or mortality with regard to the neoadjuvant treatment. Postoperative bleeding and hematoma occurred less frequently in the IntCTx group compared to the NoCTx and the CTx groups (2.0% vs. 5.33% vs. 5.1%). Postoperative lymph fistulas were slightly more frequent in the IntCTx group (4.1% vs. 0.3% vs. 1.6%). Patients treated within the NeoFLOT trial had a higher risk for blood transfusions (OR 5.5; 95%-KI, 2.49-12.19), whereas patients without neoadjuvant therapy had the longest ICU stay (mean 8.3 vs. CTx 4.5 vs. IntCTx 6.7 days). The results of the current study indicate that also an intensification of neoadjuvant chemotherapy with 6 preoperative cycles of FLOT does not significantly increase perioperative complications. Thus, prolonged neoadjuvant chemotherapy with FLOT is safe for patients with locally advanced GC or GEJ tumors.
Sections du résumé
BACKGROUND
Perioperative treatment is the standard of care in Western Europe for locally advanced gastric cancer (GC) and adenocarcinoma of the gastroesophageal junction (GEJ). Intensified neoadjuvant treatment within the NeoFLOT trial proved to be safe and effective. Yet, the influence of such intensification with 6 cycles of FLOT in the neoadjuvant setting has not been analyzed regarding its possible impact on perioperative results.
MATERIALS AND METHODS
A total of 537 patients were enrolled in this study; of whom, 132 had followed a standard neoadjuvant protocol (CTx), 356 had not received any neoadjuvant treatment (NoCTx), and 49 patients had undergone an intensified chemotherapy within the NeoFLOT trial (IntCTx) with 6 cycles of FLOT (5-FU, leucovorin, oxaliplatin, docetaxel) every 2 weeks.
RESULTS
Our results reveal no significant difference in perioperative morbidity or mortality with regard to the neoadjuvant treatment. Postoperative bleeding and hematoma occurred less frequently in the IntCTx group compared to the NoCTx and the CTx groups (2.0% vs. 5.33% vs. 5.1%). Postoperative lymph fistulas were slightly more frequent in the IntCTx group (4.1% vs. 0.3% vs. 1.6%). Patients treated within the NeoFLOT trial had a higher risk for blood transfusions (OR 5.5; 95%-KI, 2.49-12.19), whereas patients without neoadjuvant therapy had the longest ICU stay (mean 8.3 vs. CTx 4.5 vs. IntCTx 6.7 days).
CONCLUSION
The results of the current study indicate that also an intensification of neoadjuvant chemotherapy with 6 preoperative cycles of FLOT does not significantly increase perioperative complications. Thus, prolonged neoadjuvant chemotherapy with FLOT is safe for patients with locally advanced GC or GEJ tumors.
Identifiants
pubmed: 32040809
doi: 10.1007/s11605-019-04511-7
pii: 10.1007/s11605-019-04511-7
doi:
Substances chimiques
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
58-66Références
Starling N, Cunningham D. The role of systemic therapy for localised gastric cancer. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2006;17 Suppl 10:x115-21. doi: https://doi.org/10.1093/annonc/mdl248 .
doi: 10.1093/annonc/mdl248
Siewert JR, Bottcher K, Stein HJ, Roder JD. Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study. Annals of surgery. 1998;228(4):449-61.
doi: 10.1097/00000658-199810000-00002
Carr RM, Lynch JP. At the crossroads in the management of gastroesophageal junction carcinomas-where do we go from here? Gastrointestinal cancer research : GCR. 2008;2(5):253-5.
pubmed: 19259310
Lordick F, Mariette C, Haustermans K, Obermannova R, Arnold D, Committee EG. Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2016;27(suppl 5):v50-v7. doi: https://doi.org/10.1093/annonc/mdw329 .
doi: 10.1093/annonc/mdw329
Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D et al. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2016;27(suppl 5):v38-v49. doi: https://doi.org/10.1093/annonc/mdw350 .
doi: 10.1093/annonc/mdw350
Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. The New England journal of medicine. 2006;355(1):11-20. doi: https://doi.org/10.1056/NEJMoa055531 .
doi: 10.1056/NEJMoa055531
pubmed: 16822992
Ychou M, Boige V, Pignon JP, Conroy T, Bouche O, Lebreton G et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2011;29(13):1715-21. doi: https://doi.org/10.1200/JCO.2010.33.0597 .
doi: 10.1200/JCO.2010.33.0597
Schuhmacher C, Gretschel S, Lordick F, Reichardt P, Hohenberger W, Eisenberger CF et al. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2010;28(35):5210-8. doi: https://doi.org/10.1200/JCO.2009.26.6114 .
doi: 10.1200/JCO.2009.26.6114
Kumagai K, Rouvelas I, Tsai JA, Mariosa D, Klevebro F, Lindblad M et al. Meta-analysis of postoperative morbidity and perioperative mortality in patients receiving neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal and gastro-oesophageal junctional cancers. The British journal of surgery. 2014;101(4):321-38. doi: https://doi.org/10.1002/bjs.9418 .
doi: 10.1002/bjs.9418
pubmed: 24493117
Schulz C, Kullmann F, Kunzmann V, Fuchs M, Geissler M, Vehling-Kaiser U et al. 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. International journal of cancer Journal international du cancer. 2015;137(3):678-85. doi: https://doi.org/10.1002/ijc.29403 .
doi: 10.1002/ijc.29403
pubmed: 25530271
Thuss-Patience PC, Hofheinz RD, Arnold D, Florschutz A, Daum S, Kretzschmar A et al. Perioperative chemotherapy with docetaxel, cisplatin and capecitabine (DCX) in gastro-oesophageal adenocarcinoma: a phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO){dagger}. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2012;23(11):2827-34. doi: https://doi.org/10.1093/annonc/mds129 .
doi: 10.1093/annonc/mds129
Ferri LE, Ades S, Alcindor T, Chasen M, Marcus V, Hickeson M et al. Perioperative docetaxel, cisplatin, and 5-fluorouracil (DCF) for locally advanced esophageal and gastric adenocarcinoma: a multicenter phase II trial. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2012;23(6):1512-7. doi: https://doi.org/10.1093/annonc/mdr465 .
doi: 10.1093/annonc/mdr465
Biffi R, Fazio N, Luca F, Chiappa A, Andreoni B, Zampino MG et al. Surgical outcome after docetaxel-based neoadjuvant chemotherapy in locally-advanced gastric cancer. World journal of gastroenterology : WJG. 2010;16(7):868-74.
pubmed: 20143466
Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB 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. The lancet oncology. 2016. doi: https://doi.org/10.1016/S1470-2045(16)30531-9 .
Terashima M, Iwasaki Y, Mizusawa J, Katayama H, Nakamura K, Katai H et al. Randomized phase III trial of gastrectomy with or without neoadjuvant S-1 plus cisplatin for type 4 or large type 3 gastric cancer, the short-term safety and surgical results: Japan Clinical Oncology Group Study (JCOG0501). Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2019. doi: https://doi.org/10.1007/s10120-019-00941-z .
Al-Batran SE, Homann N, Schmalenberg H, Kopp HG, Haag GM, Luley KB et al. 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. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2017;35((suppl; abstr 4004)).
Bartlett EK, Roses RE, Kelz RR, Drebin JA, Fraker DL, Karakousis GC. Morbidity and mortality after total gastrectomy for gastric malignancy using the American College of Surgeons National Surgical Quality Improvement Program database. Surgery. 2014;156(2):298-304. doi: https://doi.org/10.1016/j.surg.2014.03.022 .
doi: 10.1016/j.surg.2014.03.022
pubmed: 24947651
Achiam MP, Jensen LB, Larsson H, Jensen LS, Larsen AC, Holm J et al. Comparative Investigation of Postoperative Complications in Patients With Gastroesophageal Junction Cancer Treated With Preoperative Chemotherapy or Surgery Alone. Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society. 2016;105(1):22-8. doi: https://doi.org/10.1177/1457496915577021 .
doi: 10.1177/1457496915577021
Springfeld C, Wiecha C, Kunzmann R, Heger U, Weichert W, Langer R et al. Influence of Different Neoadjuvant Chemotherapy Regimens on Response, Prognosis, and Complication Rate in Patients with Esophagogastric Adenocarcinoma. Annals of surgical oncology. 2015;22 Suppl 3:S905-14. doi: https://doi.org/10.1245/s10434-015-4617-x .
doi: 10.1245/s10434-015-4617-x
pubmed: 26001861
Haskins IN, Kroh MD, Amdur RL, Ponksy JL, Rodriguez JH, Vaziri K. The Effect of Neoadjuvant Chemoradiation on Anastomotic Leak and Additional 30-Day Morbidity and Mortality in Patients Undergoing Total Gastrectomy for Gastric Cancer. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2017;21(10):1577-83. doi: https://doi.org/10.1007/s11605-017-3496-9 .
doi: 10.1007/s11605-017-3496-9
Lorenzon L, Mercantini P, Ferri M, La Torre M, Sparagna A, Balducci G et al. Lymph-node ratio classification strongly correlates with cancer survivals of patients who underwent r0 resection for gastric cancer with more than 15 nodes harvested. Eur Surg Res. 2014;53(1-4):1-10. doi: https://doi.org/10.1159/000360937 .
doi: 10.1159/000360937
pubmed: 24854388
Alatengbaolide, Lin D, Li Y, Xu H, Chen J, Wang B et al. Lymph node ratio is an independent prognostic factor in gastric cancer after curative resection (R0) regardless of the examined number of lymph nodes. American journal of clinical oncology. 2013;36(4):325-30. doi: https://doi.org/10.1097/COC.0b013e318246b4e9 .
Sundelof M, Lagergren J, Ye W. Surgical factors influencing outcomes in patients resected for cancer of the esophagus or gastric cardia. World journal of surgery. 2008;32(11):2357-65. doi: https://doi.org/10.1007/s00268-008-9698-2 .
doi: 10.1007/s00268-008-9698-2
pubmed: 18716831