Preoperative (neoadjuvant) chemoradiotherapy in oesophageal cancer

Geh, J I; Crellin, A.; Glynne‐Jones, Robert

doi:10.1046/j.1365-2168.2001.01670.x

Cited by 191 publications

(157 citation statements)

References 150 publications

(152 reference statements)

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“…In patients with oesophageal adenocarcinoma long-term survival is strongly correlated with the achievement of pathological complete response (pCR) to neoadjuvant chemoradiotherapy (Walsh et al, 1996;Geh et al, 2001;Urba et al, 2001;Berger et al, 2005;Burmeister et al, 2005;Rohatgi et al, 2005). However, in the US Intergroup and OEO2 trials of preoperative chemotherapy, the pCR rates were only 2 and 4%, respectively (Kelsen et al, 1998;MRC, 2002).…”

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A phase II trial of preoperative chemotherapy with epirubicin, cisplatin and capecitabine for patients with localised gastro-oesophageal junctional adenocarcinoma

et al. 2009

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Preoperative cisplatin/fluorouracil is used for the treatment of localised oesophageal carcinoma. This phase II study aimed to assess the efficacy and safety of administering preoperative epirubicin/cisplatin/capecitabine (ECX). Patients with stage II or III oesophageal/ gastro-oesophageal junctional adenocarcinoma from one institution received 4 cycles of ECX (epirubicin 50 mg m À2 day 1, cisplatin 60 mg m À2 day 1, capecitabine 625 mg m À2 b.i.d. daily) followed by surgery. The primary end point was the pathological complete response (pCR) rate based on a Simon two-stage design. Secondary end points included overall and progression-free survival (OS/ PFS). Thirty-four patients were recruited: median age 60 years (range 41 -81), 91% male, 97% PS 0/1, 80% T3, 68% N1. Thirty-one patients completed four ECX cycles. Grade 3/4 toxicities X5% included neutropenia (62%), hand -foot syndrome (15%) and nausea/ vomiting (9%). Thirteen out of 28 (46%) evaluable patients responded to chemotherapy by EUS (X30% reduction in maximal tumour thickness). Twenty-six out of 34 (76%) patients underwent resection (R0 ¼ 73%, R1 ¼ 27%). Post-operatively, two patients died within 60 days of surgery. The pCR rate was 5.9% (95% CI 0 -14%) in the intent-to-treat population. According to the statistical design, this prompted early study termination. However, with a median follow-up of 34 months the median OS and 1-and 2-year survival rates were 17 months, 67 and 39% respectively. Median PFS was 13 months. Of the 14 relapsed patients, 10 presented with distant metastases. Preoperative ECX is feasible and well tolerated. Although associated with a low pCR rate, survival with ECX was comparable with published studies suggesting that pCR may not correlate with satisfactory outcome from preoperative chemotherapy for localised oesophageal adenocarcinoma.

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A phase II trial of preoperative chemotherapy with epirubicin, cisplatin and capecitabine for patients with localised gastro-oesophageal junctional adenocarcinoma

et al. 2009

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“…A pCR occurs in approximately 15 -30% of cases, and 3-year survival rates of approximately 60% irrespective of the applied protocol, type of histology and tumour stage are achieved (Geh et al, 2001). A further subdivision of pathological response to neoadjuvant regimens, the tumour regression grade (TRG) (Mandard et al, 1994), may also identify patterns of incomplete response that may impact on treatment outcome, and the addition of the pathologic response to pTNM staging has been recently advocated (Swisher et al, 2005).…”

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18FDG uptake during induction chemoradiation for oesophageal cancer fails to predict histomorphological tumour response

et al. 2006

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To determine whether [18 F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) could predict the pathological response in oesophageal cancer after only the first week of neoadjuvant chemoradiation. Thirty-two patients with localised oesophageal cancer had a pretreatment PET scan and a repeat after the first week of chemoradiation. The change in mean maximum standardised uptake value (SUV) and volume of metabolically active tissue (MTV) was compared with the tumour regression grade (TRG) in the final histology. Those who achieved a TRG of 1 and 2 were deemed responders and 3 -5 nonresponders. In the responders (28%), the SUV fell from 12.6 (76.3) to 8.1 (72.9) after 1 week of chemoradiation (P ¼ 0.070). In nonresponders (72%), the results were 9.7 (75.4) and 7.1 (73.8), respectively (P ¼ 0.003). The MTV in responders fell from 36.6 (722.7) to 22.3 (710.4) cm 3 (P ¼ 0.180), while in nonresponders, this fell from 35.9 (736.7) to 31.9 (752.7) cm 3 (P ¼ 0.405). There were no significant differences between responders and nonresponders. The hypothesis that early repeat FDG-PET scanning may predict histomorphologic response was not proven. This may reflect an inflammatory effect of radiation that obscures tumour-specific metabolic changes at this time. This assessment may have limited application in predicting response to multimodal regimens for oesophageal cancer.

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“…Recently, adjuvant modalities, such as chemotherapy and radiotherapy, have been explored for downstaging of the tumour and improving the prognosis after surgery. 4 Patients with a so-called Barrett's esophagus, that is intestinal metaplasia of the esophagus, are at increased risk for development of esophageal adenocarcinoma. 5 Malignant degeneration is characterized by a stepwise process from intestinal metaplasia through low-grade dysplasia and high-grade dysplasia into esophageal adenocarcinoma.…”

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Gene therapy for esophageal carcinoma: the use of an explant model to test adenoviral vectors ex vivo

Marsman¹,

Buskens²,

Wesseling³

et al. 2004

Cancer Gene Ther

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Adenoviral gene therapy might be a promising therapeutic strategy for esophageal carcinoma. However, adenoviral transduction efficacy in vivo is still limited. This efficacy can be improved by the insertion of an Arg-Gly-Asp (RGD) peptide in the HI-loop of the viral fiber knob. Indeed in established esophageal cell lines, we observed an up to six-fold improved transduction using the RGDtargeted adenovirus. Established cell lines, however, are easily transformed and do not represent the more complex in vivo histology and anatomy. Therefore, we set up an esophageal explant model using esophageal biopsies from patients. Viability is a limiting factor for this system. Cultured squamous epithelium, intestinal metaplasia and squamous cell carcinoma had a sufficient viability to study adenoviral transduction. Viability of the cultured adenocarcinoma biopsies was poor. Adenoviral transduction in the explant model was poor and was localized in particular cells. The transduction of the nontargeted and RGD-targeted adenovirus was similar in localization and efficacy. In conclusion, we established an esophageal explant system to test the transduction of adenoviral vectors ex vivo. The transduction was limited and localized in specific cells. RGD-targeted adenovirus did not show an improved transduction in this system.

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Preoperative (neoadjuvant) chemoradiotherapy in oesophageal cancer

Cited by 191 publications

References 150 publications

A phase II trial of preoperative chemotherapy with epirubicin, cisplatin and capecitabine for patients with localised gastro-oesophageal junctional adenocarcinoma

A phase II trial of preoperative chemotherapy with epirubicin, cisplatin and capecitabine for patients with localised gastro-oesophageal junctional adenocarcinoma

18FDG uptake during induction chemoradiation for oesophageal cancer fails to predict histomorphological tumour response

Gene therapy for esophageal carcinoma: the use of an explant model to test adenoviral vectors ex vivo

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