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A Randomised Clinical Trial of Neoadjuvant Chemotherapy vs. Neoadjuvant Chemoradiotherapy for Cancer of the Oesophagus or Gastro-Oesophageal Junction

Klevebro F, Alexandersson von Döbeln G, Wang N, Johnsen G, Jacobsen AB, Friesland S, et al

Ann Oncol 2016 Jan 17 [Epub ahead of print]

Editorial comment from Dr Chau:
In this manuscript the authors describe the results of a randomised trial of neoadjuvant chemotherapy (3 cycles of cisplatin and 5-fluororuracil) compared to the same chemotherapy plus radiotherapy (40Gy in 2Gy per day over 20 days) for patients with resectable oesophageal and gastroesophageal junctional carcinoma. One hundred and eighty one patients were enrolled of whom 131 (73%) had adenocarcinoma (ADC) histology, the remainder had a diagnosis of squamous cell carcinoma (SCC). The primary endpoint of the study was pathological complete response (pCR) rate; this was 9% for patients treated with chemotherapy and 28% for patients treated with chemoradiotherapy (p=0.002). When considering ADC and SCC separately the pCR rates for chemotherapy vs CRT were 7% vs 22% and 16% vs 42% respectively. There was no difference in three year overall survival between the two treatment groups (49% for patients treated with chemotherapy vs 47% for the CRT arm, p=0.77). Interestingly, per protocol analyses demonstrated a non-statistically significant trends to superior overall survival for SCC patients treated with CRT and inferior survival for adenocarcinoma patients who were treated with radiotherapy. With respect to toxicity, the trial demonstrated similar proportions of post-operative complications between the arms, although these tended to be more severe in patients who had received CRT.  As this study was designed to analyse pathological response rates rather than survival, any comparison of survival between the arms of the study is underpowered and should not be over-interpreted. This issue is further complicated by the inclusion of SCC and ADC patients who have differential sensitivities to chemotherapy and CRT. However, the subgroup analyses demonstrating a superior survival benefit for SCC patients treated with CRT are consistent with those from the CROSS trial. Most previous datasets exploring the biology of oesophageal cancer have focused on either ADC or SCC histology; the upcoming oesophageal cancer TCGA which includes both histologies may shed light on the similarities and differences between these two histologies.



Neoadjuvant therapy improves long-term survival after oesophagectomy treating oesophageal cancer, but the evidence to date is insufficient to determine which of the two main neoadjuvant therapy types, chemotherapy (nCT) or chemoradiotherapy (nCRT), is more beneficial. We aimed to compare the effects of nCT with those of nCRT.


This multicenter trial, which was conducted in Sweden and Norway, recruited 181 patients with carcinoma of the oesophagus or the gastro-oesophageal junction who were candidates for curative-intended treatment. The primary endpoint was histological complete response after neoadjuvant treatment, which has been shown to be correlated to increased long-term survival. Study participants were randomised to nCT or nCRT, followed by surgery with two-field lymphadenectomy. Three cycles of platin/5-fluorouracil were administered in both arms, while 40 Gy of concomitant radiotherapy was added in the nCRT arm.


The trial met the primary endpoint, histological complete response being achieved in 28% after nCRT, versus 9% after nCT (p=0.002). Lymph-node metastases were observed in 62% in the nCT group, versus 35% in the nCRT group (p=0.001). The R0 resection rate was 87% after nCRT and 74% after nCT (p=0.04). There was no difference in overall survival between the treatment arms.


The addition of radiotherapy to neoadjuvant chemotherapy results in higher histological complete response rate, higher R0 resection rate and a lower frequency of lymph node metastases, without significantly affecting survival.

©PubMed Central

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