Chemoradiotherapy for T3 and T4 squamous cell carcinoma of the esophagus using low-dose FP and radiation: A preliminary report

Fujiwara, Yoshinori; Kamikonya, Norihiko; Inoue, Takashi; Koishi, Kenji; Yoshikawa, Reigetsu; Nakao, Koji; Yagyu, Ryuuichirou; Nishiwaki, Manabu; Kojima, Shoudou; Nakagawa, Kazuhiko; Yamamura, Takehira

doi:10.3892/or.14.5.1177

Cited by 11 publications

(17 citation statements)

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“…Overall response rates with preoperative chemoradiotherapy (FP, 40-44 Gy) were reported to be higher than chemotherapy, 55.2%-74.4% [14,15], and pathological complete response (pCR) rates were 25%-28% [16][17][18]. Neoadjuvant chemoradiotherapy followed by surgery is expected to improve local control, the curative resection rate, and the [19,20].…”

Section: Discussionmentioning

confidence: 96%

Preoperative chemotherapy with weekly docetaxel plus low-dose cisplatin and 5-fluorouracil for stage II/III squamous cell carcinoma of the esophagus

et al. 2010

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Background. Docetaxel is a powerful anticancer agent for esophageal cancer. Preoperative combined chemotherapy with weekly docetaxel plus low-dose cisplatin and 5-fl uorouracil (DFP) followed by surgery is expected to improve the survival of patients with resectable esophageal squamous cell carcinoma. Methods. Clinical stage II/III squamous cell carcinoma patients who received DFP followed by esophagectomy (NAC group, n = 13) were compared retrospectively with patients who received surgery without preoperative DFP (Surgery group, n = 12). Not only the effi cacy and toxicity of initial chemotherapy but also morbidity and survival after esophagectomy were assessed. Results. Of 13 patients, the overall response rate was 92.3%; 30.8% (4/13) patients had CR, 61.5% (8/13) PR, 7.7% (1/13) SD, and 0 (0/13) PD. The 4 patients who achieved a pathological complete response (pCR) included 1 with cT4N1M0, 2 with cT3N1M0, and 1 with cT3N0M0. More than grade 3 toxicity of neutropenia and stomatitis occurred in 15.4% and 23.1% of patients, respectively. Leakage was 23.1% in the NAC group and 8.3% in the Surgery group. No treatment-related deaths occurred in the NAC group. Conclusions. This regimen as preoperative chemotherapy seemed to provide a high response rate and a favorable survival benefi t with acceptable toxicity and morbidity. To validate the clinical signifi cance of this protocol, a randomized trial is essential.

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Section: Discussionmentioning

confidence: 96%

Preoperative chemotherapy with weekly docetaxel plus low-dose cisplatin and 5-fluorouracil for stage II/III squamous cell carcinoma of the esophagus

et al. 2010

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“…infusion on days 1 -5 (Figure 1). Radiation therapy was performed after CDDP infusion on days 1 -5 using a linear accelerator (Mevatron KD2; Siemens, Munich, Germany) and a previously described radiation method (Fujiwara et al, 2005). Chemotherapy was combined with radiation therapy during the first week, and then radiation therapy alone was repeated for the next 3 weeks (days 8 -12, 15 -19, and 22 -26).…”

Section: Patients and Therapymentioning

confidence: 99%

“…Surgery is the treatment of choice for patients with locoregionally confined oesophageal cancer (stages II and III); however, the 5-year survival rate is less than 20%, even after curative surgery (Parkin et al, 2005). Since 1996, we have combined preoperative chemoradiotherapy (CRT) with radical surgery for the treatment of oesophageal cancers, and have reported increased resectability, a reduced incidence of both local recurrence and distant metastasis, and a better prognosis for CRT responders (Fujiwara et al, 2005). However, the benefits of CRT are controversial, and some clinical trials have shown that this preoperative strategy benefits only the 25% of patients who show a pathological complete response (CR; that is, no cancer cells in the resected specimen), whereas the remaining 75% present CRTresistant and highly aggressive cancers with lymph-node and distant metastases (Coia et al, 2000;Iyer et al, 2004).…”

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confidence: 99%

Hedgehog signal activation in oesophageal cancer patients undergoing neoadjuvant chemoradiotherapy

et al. 2008

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The zinc finger protein glioma-associated oncogene homologue 1 (Gli-1) is a critical component of the Hedgehog (Hh) signalling pathway, which is essential for morphogenesis and stem-cell renewal, and is dysregulated in many cancer types. As data were not available on the role of Gli-1 expression in oesophageal cancer progression, we analysed whether it could be used to predict disease progression and prognosis in oesophageal cancer patients undergoing neoadjuvant chemoradiotherapy (CRT). Among 69 patients with histologically confirmed oesophageal squamous cell carcinomas (ESCCs), 25 showed a pathological complete response after preoperative CRT. Overall survival (OS) was significantly associated with lymph-node metastasis, distant metastasis, and CRT, and was further correlated with the absence of both Gli-1 nuclear expression and residual tumour. All patients with Gli-1 nuclear expression (10.1%) had distant or lymph-node metastasis, and six out of seven died within 13 months. Furthermore, patients with Gli-1 nuclear-positive cancers showed significantly poorer prognoses than those without (disease-free survival: mean DFS time 250 vs 1738 months, 2-year DFS 0 vs 54.9%, P ¼ 0.009; OS: mean OS time 386 vs 1742 months, 2-year OS 16.7 vs 54.9%, P ¼ 0.001). Our study provides the first evidence that Gli-1 nuclear expression is a strong and independent predictor of early relapse and poor prognosis in ESCC after CRT. These findings suggest that Hh signal activation might promote cancer regrowth and progression after CRT.

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“…Moreover, preoperative chemoradiotherapy (CRT) has been accepted as a first-line therapy in the Unites States [4]. Since 1996, we have advocated a trimodal therapy, a combination of radical surgery with preoperative CRT, and have reported increased resectability, reduced incidence of both local recurrence and distant metastasis, and better clinical outcome for CRT responders [5]. However, the benefit of preoperative CRT over chemotherapy alone has not yet been established in Japan, and remains controversial in Europe.…”

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confidence: 99%

The oncoprotein and stem cell renewal factor BMI1 associates with poor clinical outcome in oesophageal cancer patients undergoing preoperative chemoradiotherapy

et al. 2012

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BackgroundThe polycomb group (PcG) family BMI1, acting downstream of the hedgehog (Hh) pathway, plays an essential role in the self-renewal of haematopoietic, neural, and intestinal stem cells, and is dysregulated in many types of cancer. Our recent report has demonstrated that Hh signalling activation can predict very earlier relapse of oesophageal cancers. As data were not available on the clinical role of BMI1 expression in oesophageal cancers after chemoradiotherapy (CRT), we analysed whether it could be also used to predict disease progression and prognosis in oesophageal cancer patients undergoing trimodality therapy of preoperative CRT and oesophagectomy.MethodsExpressions of BMI1 and p16INK4A, a downstream target of PcG, were analysed in 78 patients with histologically confirmed oesophageal squamous cell carcinoma (ESCC) after preoperative CRT by immunohistochemical staining. The association of BMI1 and p16INK4A expression with clinicopathologic characteristics was analysed by χ2-test. Survival analysis was carried out by the log-rank test using Kaplan-Meier method.ResultsAmong 78 ESCC patients, 24 patients (30.8%) showed BMI1 positivity, mainly localised in the nuclei of tumour cells. Patients harbouring BMI1-positive tumour cells showed significantly poorer prognoses than those without such cells or residual tumours (mean disease-free survival (DFS) time 16.8 vs 71.2 months; 3-yr DFS 13.3% vs 49.9%, P=0.002; mean OS time 21.8 vs 76.6 months; 3-yr OS 16.2% vs 54.9%, P=0.0005). There was no significant correlation between p16INK4A expression and BMI1 expression.ConclusionsOur study shows that BMI1 expression is a predictor of early relapse and poor prognosis in ESCC after CRT. These findings suggest that BMI1 signal activation might be involved in promoting cancer regrowth and progression after CRT, and might be indicative of emergence of ‘more aggressive’ cancer progenitor cells.

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Chemoradiotherapy for T3 and T4 squamous cell carcinoma of the esophagus using low-dose FP and radiation: A preliminary report

Cited by 11 publications

References 0 publications

Preoperative chemotherapy with weekly docetaxel plus low-dose cisplatin and 5-fluorouracil for stage II/III squamous cell carcinoma of the esophagus

Preoperative chemotherapy with weekly docetaxel plus low-dose cisplatin and 5-fluorouracil for stage II/III squamous cell carcinoma of the esophagus

Hedgehog signal activation in oesophageal cancer patients undergoing neoadjuvant chemoradiotherapy

The oncoprotein and stem cell renewal factor BMI1 associates with poor clinical outcome in oesophageal cancer patients undergoing preoperative chemoradiotherapy

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