Neoadjuvant chemotherapy or chemoradiation for patients with advanced adenocarcinoma of the oesophagus? A propensity score-matched study

doi:10.1016/j.ejso.2017.06.003

European Journal of Surgical Oncology (EJSO)

Volume 43, Issue 8, August 2017, Pages 1572-1580

https://doi.org/10.1016/j.ejso.2017.06.003 Get rights and content

Abstract

Background

Multimodal therapies are the standard of care for advanced adenocarcinomas of the oesophagus and gastro-oesophageal junction (AEG Types I and II). Only three randomised trials have compared preoperative chemotherapy with and without radiation. The results showed a small benefit for combined chemoradiation. In the meantime, newer therapy protocols are available.

Aim

In a propensity-score matched study, we analysed patients with locally advanced AEG type I or II, treated with chemotherapy (FLOT-protocol) or chemoradiation (CROSS-protocol), followed by oesophagectomy, in a single high-volume centre.

Patients and methods

Between 2011 and 2015, 137 patients with advanced (cT3NxcM0) adenocarcinoma received pre-operative therapy; 70% had chemoradiation (CROSS-protocol) and 30% had chemotherapy (FLOT-protocol). After propensity-score matching, 40 patients from the CROSS-group were selected for analysis. Postoperative histopathological response and prognosis were analysed.

Results

The two groups were comparable according to the matching criteria age, gender, tumour location, and year of surgery. R0-resection was achieved in 97% of patients in the CROSS-group and 85% of the FLOT-group (p = 0.049). Major response of the primary tumour was evident more often in the CROSS-group (17/40 pts. 43%) versus FLOT-group (11/40 pts. 27%) as well no lymph node metastasis (ypN0 = 68% versus ypN0 = 40%) (p = 0.014). Prognosis were not significantly different between the two groups. In multivariate analysis, only ypN-category was an independent prognostic factor.

Conclusion

Compared to FLOT-chemotherapy, neoadjuvant chemoradiotherapy with the CROSS-protocol in locally advanced adenocarcinoma AEG types I and II resulted in better response by the primary tumour and less lymph node metastasis but without superior survival.

Introduction

Oesophageal cancer is one of the most common and deadly tumours worldwide.¹ Incidence of adenocarcinoma (AC) of the oesophagogastric junction (GEJ) is increasing more than all other gastrointestinal cancer types.2, 3 Siewert et al. classified these carcinomas according to the location of the tumors as AEG type I = AC of the distal oesophagus and AEG type II = AC of the gastroesophageal junction.⁴ These carcinomas and AC of the stomach are different tumour entities but often they have been investigated together in the medical literature.5, 6 In the majority of cases, oesophageal cancer is diagnosed in a locally-advanced or systemic stage. In recent decades, researchers have investigated different regimens of chemo- and chemoradio-based adjuvant, neoadjuvant, and peri-operative therapies compared to surgery alone.7, 8

In 2006, the MAGIC-Trial⁸ initially underscored the survival benefit for patients receiving peri-operative (before and after surgery) chemotherapy. However, the patients enrolled had gastric adenocarcinoma and few cases of AEG tumours. In the interim, perioperative treatment has become the standard of care for locally advanced gastroesophageal cancer (gastric and AEG adenocarcinoma).⁹ In addition, newer protocols for chemotherapy like FLOT (5-fluoruracil/leucovorin, oxaliplatin and docetaxel) have been introduced, with improved response.10, 11, 12

In 2011, Sjoquist et al.⁷ published an updated meta-analysis and enrolled 24 studies with 4188 patients. Neoadjuvant radiochemotherapy showed better results with 8.7% improved 2-year survival rate after chemoradiation compared to 5.1% improvement after only chemotherapy.

In 2012, a Dutch multi-centre trial presented results of CROSS; it was designed to assess benefits for patients with resectable oesophageal cancer after neoadjuvant radiochemotherapy followed by surgery vs. surgery alone. Preoperative chemoradiation with 41 Gy, carboplatin and paclitaxel improved survival by 7% in 5 years in patients with AC compared to surgery alone.¹³

In order to clarify which pre-operative therapy might yield better results, we designed a propensity score-matched study to evaluate patients with locally advanced AEG type I and II treated with neoadjuvant chemotherapy (FLOT-protocol) or chemoradiation (CROSS-protocol) followed by Ivor-Lewis hybrid oesophagectomy, in a single high-volume centre. The primary endpoint was the combined response of the tumor and the lymph nodes according to Hölscher et al.¹⁴ Secondary endpoints were the rate of R0-resection and overall survival.

Section snippets

Patients

Data were analysed after propensity score matching from our pool of patients treated at the Department of General, Visceral and Cancer Surgery, University of Cologne, Germany.

Between January 2011 and March 2015, 137 patients with advanced (cT3cNx cM0) AEG type I or II received preoperative therapy; 97 (70%) had preoperative chemoradiation (according to the CROSS-protocol) and 40 (30%) had chemotherapy (according to the FLOT-protocol). After propensity score matching, 40 patients from the CROSS

Demographics

After propensity score matching, our study population consisted of 40 patients undergoing the FLOT-protocol and 40 matched patients undergoing the CROSS-protocol.

Patients of both groups did not differ significantly according to the matching criteria: 35 (88%) males and five (12%) females received CROSS, 38 (95%) males and two (5%) females received FLOT (p = 0.235); median age was 61.5 years in both groups: min = 43y, max = 76y in the CROSS group and min = 28y, max = 78y in the FLOT group

Discussion

In recent decades, many experimental studies have been published worldwide to define the best therapy for locally advanced oesophageal cancer (Table 2).5, 8, 19, 20, 21, 22, 23 Various protocols have been administered to patients affected by different histologic types of cancer, in pre-operative stages, and undergoing several surgical procedures.

In the 2012 (latest) edition, EORTC guidelines summarized state of the art for multimodality therapies for gastroesophageal adenocarcinoma. For AC of

Conclusion

On comparison, neoadjuvant chemoradiotherapy with 41.4 Gy and carboplatin and paclitaxel (CROSS-protocol), performs better than chemotherapy with 5-fluoruracil/leucovorin, oxaliplatin and docetaxel (FLOT-protocol) prior to surgery in locally advanced adenocarcinoma of the distal oesophagus or oesophagogastric junction (AEG types I and II) in terms of primary tumour response and lymph node metastasis. The existence of LNM was the only independent prognostic factor. According to these results,

Conflict of interest

All authors have declared no conflicts of interest.

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Neoadjuvant chemotherapy or chemoradiation for patients with advanced adenocarcinoma of the oesophagus? A propensity score-matched study

Abstract

Background

Aim

Patients and methods

Results

Conclusion

Introduction

Section snippets

Patients

Demographics

Discussion

Conclusion

Conflict of interest

Lancet Oncol

Eur J Cancer

Lancet Oncol

Ann Oncol

Eur J Cancer

Ann Oncol

Global cancer statistics

CA Cancer J Clin

Demographic variations in the rising incidence of esophageal adenocarcinoma in white males

Cancer

Trends in esophageal cancer incidence by histology, United States, 1998-2003

Int J Cancer

Cardia cancer: attempt at a therapeutically relevant classification

Chirurg

Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial

J Clin Oncol

Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781

J Clin Oncol

Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer

N Engl J Med

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

A pilot trial of FLOT neoadjuvant chemotherapy for resectable esophagogastric junction adenocarcinoma

Med Oncol

Preoperative chemoradiotherapy for esophageal or junctional cancer

N Engl J Med