Definitive Chemoradiotherapy for T4 and/or M1 Lymph Node Squamous Cell Carcinoma of the Esophagus

Ohtsu, Atsushi; Boku, Narikazu; Muro, Kei; Chìn, Keisho; Muto, Manabu; Yoshida, Shigeaki; Satake, Mitsuo; Ishikura, Satoshi; Ogino, Takashi; Miyata, Yoshinori; Seki, Shu; Kaneko, Kazuhiro; Nakamura, Akira

doi:10.1200/jco.1999.17.9.2915

Cited by 404 publications

(396 citation statements)

References 16 publications

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“…However, it should be pointed out that three of them responded to the treatment, one obtained a pCR and another is one of the four long living. These findings are similar to the results reported by Ohtsu et al (1999)) and Polee et al (2003)) and support the concept that chemoradiotherapy has the same curative potential, for locally advanced disease, irrespective of mediastinal or M1a node extension; therefore, separating these groups is not strictly necessary. The utility of surgical resection after chemoradiotherapy in advanced oesophageal cancer is still not established; in spite of this, we offered responding patients the possibility of resection, as this was the best way to ascertain the rate of complete response, and residual tumour resection could be beneficial.…”

Section: Discussionsupporting

confidence: 90%

“…The high percentage of fistulisation observed might be explained by the prevalence of T4 lesions, localised mostly in the upper or middle portion of the oesophagus. The high risk of treatment-related perforation of the oesophageal wall in T4 oesophageal patients was also highlighted by Ohtsu et al (1999). In order to reduce the perforation risk, we decided to use induction chemotherapy, before chemoradiotherapy, with the hope of decreasing the tumour volume before encountering severe oesophagitis and stomatitis.…”

Section: Discussionmentioning

confidence: 99%

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Phase II trial of docetaxel, cisplatin and fluorouracil followed by carboplatin and radiotherapy in locally advanced oesophageal cancer

Chiarion-Sileni

Corti

Ruol³

et al. 2007

Br J Cancer

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This study was performed to assess the efficacy and safety of docetaxel, cisplatin and fluorouracil combination in patients with unresectable locally advanced oesophageal squamous cell carcinoma. Treatment consisted of docetaxel 60 mg m À2 , cisplatin 75 mg m À2 on day 1 and fluorouracil 750 mg m À2 day À1 on days 2 -5, repeated every 3 weeks for three cycles, followed by carboplatin 100 mg m À2 week À1 for 5 weeks and concurrent radiotherapy (45 Gy in 25 fractions, 5 days week À1 ). After radiotherapy, eligible patients either underwent an oesophagectomy or received high dose rate endoluminal brachytherapy (HDR-EBT). Thirty-one out of 37 enrolled patients completed the planned chemotherapy and 30 completed chemoradiation. After completion of chemotherapy, 49% (95% CI: 32.2 -66.2) had a clinical response. Twelve patients (32%) underwent a resection, which was radical in 60% (postoperative mortality: 0%). A pathological complete response was documented in four patients (11% of enrolled, 30% of resected). The median survival was 10.8 months (95% CI: 8.1 -12.4), and the 1-and 2-year survival rates were 35.1 and 18.9%, respectively. Grade 3 -4 toxicities were neutropoenia 32%, anaemia 11%, non-neutropoenic infections 18%, diarrhoea 6% and oesophagitis 5%. Nine patients (24%) developed a tracheo-oesophageal fistula during treatment. Even if the addition of docetaxel to cisplatin and 5-fluorouracil (5-FU) seems to be more active than the cisplatin and 5-FU combination, an incremental improvement in survival is not seen, and the toxicity observed in this study population is of concern. In order to improve the prognosis of these patients, new drugs, combinations and strategies with a better therapeutic index need to be identified.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Phase II trial of docetaxel, cisplatin and fluorouracil followed by carboplatin and radiotherapy in locally advanced oesophageal cancer

Chiarion-Sileni

Corti

Ruol³

et al. 2007

Br J Cancer

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“…A literature search produced no other studies that specifically investigated chemoradiotherapy for locally advanced disease, such as T4 and/or M1 LYM. In our previous study, a CR rate of 33% and a 3-year survival rate of 23% were achieved in patients with unresectable T4 tumours and/or M1 LYM disease (Ohtsu et al, 1999), suggesting that concurrent chemoradiotherapy was potentially curative for locally advanced carcinoma. In our present study, a CR rate of 39% and a 3-year survival rate of 19% were achieved in patients with 'severe dysphagia' accompanied by T3 or T4 disease.…”

Section: Discussionmentioning

confidence: 85%

“…In a prospective randomised trial by the Radiation Therapy Oncology Group, which compared chemoradiotherapy with radiotherapy alone, the combined-modality arm demonstrated a significant improvement of survival (Herskovic et al, 1992), with a 5-year survival rate of 27%, compared with 0% for radiotherapy alone (Al-Sarraf et al, 1997). With regard to the indications of chemoradiotherapy as a curative treatment for patients with locally advanced diseases, our multicentre study suggested that concurrent chemoradiotherapy was potentially curative even in cases with locally advanced carcinoma of the oesophagus (i.e., T4 and/or M1 lymph node metastasis (LYM) disease) (Ohtsu et al, 1999). Of the 54 patients in that study, 18 (33%) achieved a complete response, and the 3-year survival rate was 23%.…”

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confidence: 80%

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Definitive chemoradiotherapy for patients with malignant stricture due to T3 or T4 squamous cell carcinoma of the oesophagus

et al. 2003

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We retrospectively investigated the efficacy and feasibility of concurrent chemoradiotherapy for patients with severe dysphagia caused by oesophageal squamous cell carcinoma. Concurrent chemoradiotherapy was performed in 57 patients with T3 or T4 disease containing M1 lymph node (LYM) disease. Chemotherapy consisted of protracted infusion of 5-fluorouracil (5-FU) 400 mg m À2 24 h À1 on days 1 -5 and 8 -12, combined with 2-h infusion of cisplatin (CDDP) 40 mg m À2 on days 1 and 8. Radiation treatment at a dose of 30 Gy in 15 fractions of the mediastinum was administered concomitantly with chemotherapy. A course schedule with 3-week treatment and a 1 to 2-week break was applied twice, with a total radiation dose of 60 Gy, followed by two or more courses of 5-FU and CDDP. In all, 24 patients (42%) achieved a complete response, and the 3-year survival rate was 19%. Major toxicities were leukocytopenia and oesophagitis, and there were two (4%) treatment-related deaths. In contrast, 22 patients with T3 disease survived longer than 35 patients with T4 disease (P ¼ 0.001); however, the survival rate in 15 patients with M1 LYM disease did not differ significantly from that in 42 patients without M1 LYM disease (P ¼ 0.3545). Our results indicate that definitive chemoradiotherapy is potentially curative for locally advanced oesophageal carcinoma with malignant stricture. The efficacy and survival of patients treated with this regimen are related to the T factor.

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Treatment and clinical outcome of clinical T4 esophageal cancer: A systematic review

Makino

Yamasaki

Miyazaki

et al. 2018

Annals of Gastroent Surgery

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Background Survival of patients with cT4 esophageal cancer is dismal. Although the optimal treatment strategy remains to be established, two treatment options are available for cT4 esophageal cancers: definitive chemoradiation (dCRT) and induction treatment followed by conversion surgery (CS). However, little is known concerning the differences in clinical outcome between patients with T4 esophageal tumors treated with dCRT and those eventually treated with CS. Methods A systematic search of the scientific literature on PubMed/MEDLINE was carried out using the keywords “T4 esophageal cancer,” “invading (involving) adjacent organ,” “definitive chemoradiation,” “induction therapy,” “salvage surgery,” and “conversion surgery,” obtaining 28 reports published up to July 2018. Results/Conclusion We found that CS was superior to dCRT with respect to local disease control and short‐term survival; however, CS was associated with relatively higher perioperative mortality and morbidity. Alternatively, although dCRT might often cause fistula formation, a clinical complete response to dCRT is likely to lead to a better prognosis. Recent advances in chemotherapeutic agents have led to triple induction chemotherapy, with docetaxel, cisplatin, and 5‐fluorouracil (DCF), which has shown promise as an initial induction treatment for cT4 esophageal cancer. Indeed, this regimen could control both local and systemic disease, which enables curative resection without preoperative CRT. Moreover, some appropriate changes in perioperative management and intensive systemic chemotherapy might enhance patient outcome. Randomized controlled trials with a large sample size are needed to establish the standard treatment for cT4 esophageal cancer.

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Definitive Chemoradiotherapy for T4 and/or M1 Lymph Node Squamous Cell Carcinoma of the Esophagus

Abstract: Despite its significant toxicity, this combined modality seemed to have curative potential even in cases of locally advanced carcinoma of the esophagus.

Cited by 404 publications

References 16 publications

Phase II trial of docetaxel, cisplatin and fluorouracil followed by carboplatin and radiotherapy in locally advanced oesophageal cancer

Phase II trial of docetaxel, cisplatin and fluorouracil followed by carboplatin and radiotherapy in locally advanced oesophageal cancer

Definitive chemoradiotherapy for patients with malignant stricture due to T3 or T4 squamous cell carcinoma of the oesophagus

Treatment and clinical outcome of clinical T4 esophageal cancer: A systematic review

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