Real-life data on improvement of survival after perioperative chemotherapy versus surgery alone on resectable adenocarcinoma of the stomach – a single-center study^[*]

Abstract

Background In the last decade, neoadjuvant chemotherapy has become the standard of care also for curatively resectable advanced gastric cancer. Prospective randomized studies have shown a significant benefit in disease free and overall survival rate after perioperative chemotherapy as compared to immediate surgery. However, data in the “real-life” setting are rare. In our retrospective study, we wanted to clarify the question whether this benefit is achievable under real-life conditions.

Methods A total of 81 patients with resected adenocarcinoma of the stomach or distal esophagogastric junction (AEG III) clinical stage II–IIIc according to UICC (eighth edition) were enrolled. Forty-two patients received perioperative chemotherapy (cohort 1) and 39 patients were operated on immediately (cohort 2). Chemotherapy was carried out according to the ECF, EOX, or FLOT protocols.

Results Overall 5-year survival was 35.7 % in cohort 1 and 23.7 % in cohort 2. Thus, the relative 5-year overall survival benefit was 51 %, and 12 % in absolute numbers (p = 0.083). For patients receiving perioperative chemotherapy per protocol (n = 20), a more marked absolute improvement in 5-year overall survival of 16.3 % as compared to immediately operated on patients was achieved (p = 0.05). Progression-free survival in this analysis was shown to be improved by perioperative chemotherapy also without statistical significance (p = 0.03).

Conclusions Patients with curatively resectable gastric adenocarcinoma or type III AEG tumor benefit from perioperative chemotherapy in terms of overall survival even under real-life conditions. Moreover, a benefit in progression-free survival can be demonstrated.

Zusammenfassung

Hintergrund Im letzten Jahrzehnt wurde eine perioperative Chemotherapie zum Standard auch bei potentiell kurativ resektablen Magenkarzinomen. Prospektiv randomisierte Studien haben einen signifikanten Vorteil im krankheitsfreien und Gesamt-Überleben nach perioperativer Chemotherapie im Vergleich zu alleiniger Resektion gezeigt. Daten zur „Real-Life-Situation“ sind jedoch spärlich. In unserer retrospektiven Studie wollten wir klären, ob sich diese Vorteile auch unter real-life-Bedingungen nachvollziehen lassen.

Methoden Eingeschlossen wurden insgesamt 81 Patienten mit resektablem Adenokarzinom des Magens oder distalen ösophagogastralen Übergangs (AEG Typ III) im klinischen Stadium II–IIIc (UICC, 8. Auflage). 42 Patienten erhielten eine perioperative Chemotherapie (Kohorte 1), 39 Patienten wurden direkt einer Operation zugeführt (Kohorte 2). Die Chemotherapie erfolgte nach dem ECF, EOX- oder FLOT-Protokoll.

Ergebnisse Das 5-Jahres-Überleben betrug 35,7 % in Kohorte 1 und 23,7 % in Kohorte 2 (relativer Unterschied 51 %, absoluter Unterschied 12 %, p = 0,083) Vergleicht man Patienten, die die perioperative Chemotherapie nach Protokoll erhielten (n = 20) mit den direkt operierten, wurde eine Verbesserung des Gesamtüberlebens um 16,3 % erreicht (p = 0,05). Im progressionsfreien Überleben wurde in dieser Analyse ebenfalls eine nicht signifikante Verbesserung durch perioperative Chemotherapie beobachtet (p = 0,03).

Schlussfolgerung Patienten mit potentiell kurativ resektablem Magenkarzinom profitieren in Bezug auf das Gesamtüberleben und progressionsfreiem Überleben auch unter real-life-Bedingungen deutlich von einer perioperativen Chemotherapie.

Key words

gastric cancer - gastric adenocarcinoma-neoadjuvant chemotherapy - perioperative chemotherapy - real-life data

Schlüsselwörter

Magenkarzinom - neoadjuvante Chemotherapie - perioperative Chemotherapie - Real-life-Daten

• References

• 1 Chon SH, Berlth F, Plum PS. et al. Gastric cancer treatment in the world: Germany. Transl Gastroenterol Hepatol 2017; 2: 53-55
• 2 Roder JD, Böttcher K, Siewert JR. et al. Prognostic factors in gastric carcinoma. Results of the German Gastric Carcinoma Study 1992. Cancer 1993; 72: 2089-2097
• 3 Bonenkamp JJ, Hermans J, Sasako M. et al. Extended lymph-node dissection for gastric cancer. N Engl J Med 1999; 340: 908-914
• 4 Cuschieri A, Weeden S, Fielding J. et al. Patient survival after D1 and D2 resections for gastric cancer: long-term results of the MRC randomized surgical trial. Br J Cancer 1999; 79: 1522-1530
• 5 Wilke H, Preusser P, Fink U. et al. Preoperative chemotherapy in locally advanced and nonresectable gastric cancer: a phase II study with etoposide, doxorubicin, and cisplatin. J Clin Oncol 1989; 7: 1318-1326
• 6 Cascinu S, Labianca R, Graziano F. et al. Intensive weekly chemotherapy for locally advanced gastric cancer using 5-fluorouracil, cisplatin, epidoxorubicin, 6S-leucovorin, glutathione and filgrastim: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD). Br J Cancer 1998; 78: 390-393
• 7 Menges M, Schmidt C, Lindemann W. et al. Low toxic neoadjuvant cisplatin, 5-fluorouracil and folinic acid in locally advanced gastric cancer yields high R-0 resection rate. J Cancer Res Clin Oncol 2003; 129: 423-429
• 8 Cunningham D, Allum WH, Stenning SP. et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006; 355: 11-20
• 9 Ychou M, Boige V, Pignon JP. et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 2011; 29: 1715-1721
• 10 Coccolini F, Nardi M, Montori G. et al. Neoadjuvant chemotherapy in advanced gastric and esophago-gastric cancer. Meta-analysis of randomized trials. Int J Surg 2018; 51: 120-127
• 11 Reddavid R, Sofia S, Chiaro P. et al. Neoadjuvant chemotherapy for gastric cancer. Is it a must or a fake?. World J Gastroenterol 2018; 24: 274-289
• 12 van Hagen P, Hulshof MC, van Lanschot JJ. et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012; 366: 2074-2084
• 13 Cunningham D, Rao S, Starling N. et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 2008; 358: 36-46
• 14 Al-Batran SE, Hartmann JT, Hofheinz R. et al. Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol 2008; 19: 1882-1887
• 15 Cats A, Jansen EPM, van Grieken NCT. et al. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol 2018; 19: 616-628
• 16 Reynolds JV, Preston SR, O’Neill B. et al. ICORG 10–14: NEOadjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study (Neo-AEGIS). BMC Cancer 2017; 17: 401