Long-term Follow-up of a Randomized Phase II Study of Cisplatin/5-FU Concurrent Chemoradiotherapy for Esophageal Cancer (KROSG0101/JROSG021)

Nishimura, Yasumasa; Hiraoka, Masahiro; Koike, Ryuta; Nakamatsu, Kiyoshi; Itasaka, Satoshi; Kawamura, Masashi; Negoro, Yuji; Araki, Norio; Ishikawa, Hitoshi; Fujii, Takashi; Mitsuhashi, Norio

doi:10.1093/jjco/hys112

Cited by 37 publications

(25 citation statements)

References 19 publications

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“…We suggest therefore that lower cervical and upper mediastinal nodes should be included in the CTV, especially LNs of 101 (specifically 101R), 105 and 106Rec. This is in accordance with the historically small T‐shaped field radiation and with the current RTOG guidelines …”

Section: Discussionsupporting

confidence: 90%

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Distribution of lymph node metastases on FDG‐PET/CT in inoperable or unresectable oesophageal cancer patients and the impact on target volume definition in radiation therapy

et al. 2016

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Our results show a good correlation between the distribution of nodal volumes at risk in surgical series and on FDG-PET/CT. The results can be used to determine target definition in dCRT for oesophageal cancer. For mid-thoracic tumours, the current target delineation guidelines may be extended based on the risk of node involvement, but more clinical studies are needed to determine if the potential harm of expanding the CTV outweighs the potential benefit.

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Section: Discussionsupporting

confidence: 90%

“…This is in accordance with the historically small T-shaped field radiation and with the current RTOG guidelines. 13,15 Mid-thoracic tumours…”

Section: Proximal Tumoursmentioning

confidence: 99%

Distribution of lymph node metastases on FDG‐PET/CT in inoperable or unresectable oesophageal cancer patients and the impact on target volume definition in radiation therapy

et al. 2016

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“…For more advanced stages, chemotherapy has shown favorable results. Combinations of cisplatin and other drugs, such as paclitaxel, docetaxel, and 5-fluorouracil (CF), are standard chemotherapy regimens for advanced ESCC [4–6]. Cisplatin, a molecule that can enter the cell, interferes with the process of DNA synthesis, resulting in inhibition of DNA replication and cell cycle arrest, DNA damage, and subsequent apoptosis and necrosis [7 8].…”

Section: Introductionmentioning

confidence: 99%

Krüppel-Like Factor 4 Enhances Sensitivity of Cisplatin to Esophageal Squamous Cell Carcinoma (ESCC) Cells

Chen

Zhang

et al. 2017

Med Sci Monit

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BackgroundThe aim of this study was to elucidate the role of Krüppel-Like factor 4 (KLF4) in cisplatin resistance in esophageal squamous cell carcinoma (ESCC) cells, which may eventually help to improve the treatment efficacy.Material/MethodsHuman esophageal squamous cell carcinoma (ESCC) cell line CaEs-17, TE-1, EC109, KYSE510, KYSE140, KYSE70, and KYSE30 were selected to detect their sensitivity to cisplatin. 5-Azacytidine-2′-deoxycytidine (5′-Aza-CdR) treatment and methylation-specific PCR (MS-PCR) were used to detect the methylation status for KLF4. Cell viability, apoptosis, and cell cycle were measured using methyl thiazolyl tetrazolium (MTT) assay, Annexin V affinity assay, and flow cytometry, respectively.ResultsThe sensitivity to cisplatin was different in the seven ESCC cell lines, with TE-1 having the lowest sensitivity and KYSE140 having the highest sensitivity. Interestingly, the level of KLF4 was relatively low in TE-1 cells; while it was high in KYSE140 cells. These results suggested that KLF4 may be involved in cisplatin resistance. The promoter region was mostly unmethylated in KYSE140 cells; while it was hypermethylated in TE-1 cells. After treatment with demethylation reagent 5-Aza-CdR, cisplatin sensitivities were significantly increased after upregulation of KLF4, as the IC50 values were significantly decreased in the TE-1 cell treated with 5-Aza-CdR. Furthermore, upregulation of KLF4 induced cell apoptosis and cell cycle arrest at S phase.ConclusionsKLF4 enhances the sensitivity of cisplatin to ESCC cells through apoptosis induction and cell cycle arrest. Our data provided a novel insight to the mechanism of cisplatin resistance; overexpression of KLF4 may be a potential therapeutic strategy for cisplatin resistance in human ESCC.

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“…In a single institute phase II trial of chemoradiotherapy with 5-FU and cisplatin and 60 Gy irradiation for patients with clinical T4 and/or M1 lymph node ESCC, complete response (CR) rate was 33 % and median survival time and 3-year survival rate were 9 months and 23 %, respectively [6]. Another clinical trials of 5-FU and cisplatin and 60 Gy irradiation for patients including clinical T4 showed that CR rate was 15-33 % and 2-year, 3 year survival rates were 27-46 % and 23-30 %, respectively [7,8,[42][43][44]. Other combination regimen using new drugs (paclitaxel, docetaxel, oxaliplatin, S-1, and cetuximab) with concurrent radiotherapy have been evaluated [46][47][48][49].…”

Section: Chemoradiotherapy For Unresectable Locallymentioning

confidence: 99%

“…Late adverse events are pericardial effusion, pleural effusion, esophageal strictures, fistula formation, and hemorrhage [70]. And hypothyroidism may occur in case of including the thyroid within radiation field [44]. In a Japanese study, long-term analysis of 78 patients with complete remission treated with definitive chemoradiotherapy (cisplatin and 5-FU with 60 Gy) for squamous cell carcinoma revealed grade 2, 3, and 4 late pericarditis occurring in 6, 5, and 1 % of patients, respectively; grade 4 heart failure in two patients; grade 2, 3, and 4 pleural effusion development in 5, 6, and 0 % of patients, respectively; and grade 2, 3, and 4 radiation pneumonitis development in 1, 2, and 0 % of patients, respectively [71].…”

Section: Toxicity Of Radiotherapymentioning

confidence: 99%

Radiation Therapy

Ito¹

2014

Esophageal Squamous Cell Carcinoma

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Radiotherapy is indicated for the treatment of esophageal cancer both with curative intent and with palliative intent. Concurrent chemoradiotherapy is the standard treatment for patients in good condition who can receive chemotherapy, based on the result of randomized trial that compared chemoradiotherapy with radiotherapy alone. For locally advanced unresectable esophageal cancer, definitive chemoradiotherapy is the standard therapy with potentially curative intent. And for resectable esophageal cancer, definitive chemoradiotherapy is a treatment option in an attempt to preserve the esophagus from favorable results of clinical trials. These results are supported by salvage treatment in cases of residual or recurrent disease after chemoradiotherapy. However high mortality rate of salvage surgery and high incidence of late toxicities after chemoradiotherapy with higher radiation dose are important problems to be solved. Neoadjuvant chemoradiotherapy is standard treatment for locally advanced esophageal cancer in Western countries; however it is investigational in Japan. Combination chemotherapy of new agents and new radiotherapy technique such as intensity-modulated radiation therapy, protonbeam therapy, and heavy-particle radiotherapy have been evaluated in clinical trials to improve the treatment results including efficacy and toxicity.

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Long-term Follow-up of a Randomized Phase II Study of Cisplatin/5-FU Concurrent Chemoradiotherapy for Esophageal Cancer (KROSG0101/JROSG021)

Cited by 37 publications

References 19 publications

Distribution of lymph node metastases on FDG‐PET/CT in inoperable or unresectable oesophageal cancer patients and the impact on target volume definition in radiation therapy

Distribution of lymph node metastases on FDG‐PET/CT in inoperable or unresectable oesophageal cancer patients and the impact on target volume definition in radiation therapy

Krüppel-Like Factor 4 Enhances Sensitivity of Cisplatin to Esophageal Squamous Cell Carcinoma (ESCC) Cells

Radiation Therapy

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