Concomitant Chemotherapy and External Radiotherapy plus Brachytherapy for Locally Advanced Esophageal Cancer Results of a Retrospective Multicenter Study
M. TessaP RottaRiccardo RagonaB SolaMario GrassiniDaniela NassisiPiera SciaceroMario AiroldiAndrea Riccardo FilippiLuca GianelloClaudio De AngelisFranca OzzelloAlessandro Boidi TrottiUmberto RicardiG.L. Sannazzari
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Aims and Background In October 1995, the Piedmont AIRO (Italian Society of Radiation Oncology) Group started a multi-institutional study of radiochemotherapy on locally advanced esophageal cancer, characterized by external radiotherapy followed by an intraluminal high dose-rate brachytherapy boost. Most patients were re-evaluated for surgery at the end of the program. The primary aim of the study was to assess efficacy of curative radiochemotherapy regarding overall survival and local control rates. The secondary aim was to evaluate the ability of radiochemotherapy to make resectable lesions previously considered inoperable. Methods and Study Design Between January 1996 and March 2000, 75 patients with locally advanced esophageal cancer were enrolled. All were treated with definitive radiotherapy; due to age or high expected toxicity, chemotherapy was employed only in 53 of them. Treatment schedule consisted of 60 Gy external radiotherapy (180 cGy/d, 5 days/week for 7 weeks) concomitant with two 5-day cycles of chemotherapy with cisplatin and fluorouracil (weeks 1 and 5). One or two sessions of 5-7 Gy intraluminal high dose-rate brachytherapy were carried out on patients whose restaging showed a major tumor response. Surgery was performed in 14 patients. Results At the end of radiotherapy, dysphagia disappeared in 46/75 cases (61%), and in 20/75 (27%) a significant symptom reduction was recorded. Complete objective response at restaging after radiotherapy was obtained in 33% of patients and a partial response in 53%. At the end of the multimodal treatment program, including esophagectomy, complete responses were 34 (45%); 4 of 14 (28.5%) cases proved to be disease free (pTO) at pathological examination. No G3-G4 toxicity was recorded. Two- and 5-year overall survival rates of all patients were, respectively, 38% and 28%; 2- and 5-year local control rates were, respectively, 35% and 33%. In a subgroup of 20 nonsurgical patients in complete response after radiochemotherapy, the overall survival rate at 3 and 5 years was 65% and the local control rate at 3 and 5 years was 75%. According to multivariate analysis, prognostic factors for survival were Karnofsky index and esophagectomy. Conclusions For patients with locally advanced disease, radiochemotherapy showed improved clinical and pathologic tumor response and survival compared to surgery or radiotherapy alone. Intraluminal brachytherapy with a small fraction size allows an increased dose to the tumor without higher toxicity. Esophagectomy following radiochemotherapy could improve survival rates compared to definitive radiochemotherapy, but it is necessary to optimize selection criteria for surgery at the re-evaluation phase.Keywords:
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Esophagectomy
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Aims and Background In October 1995, the Piedmont AIRO (Italian Society of Radiation Oncology) Group started a multi-institutional study of radiochemotherapy on locally advanced esophageal cancer, characterized by external radiotherapy followed by an intraluminal high dose-rate brachytherapy boost. Most patients were re-evaluated for surgery at the end of the program. The primary aim of the study was to assess efficacy of curative radiochemotherapy regarding overall survival and local control rates. The secondary aim was to evaluate the ability of radiochemotherapy to make resectable lesions previously considered inoperable. Methods and Study Design Between January 1996 and March 2000, 75 patients with locally advanced esophageal cancer were enrolled. All were treated with definitive radiotherapy; due to age or high expected toxicity, chemotherapy was employed only in 53 of them. Treatment schedule consisted of 60 Gy external radiotherapy (180 cGy/d, 5 days/week for 7 weeks) concomitant with two 5-day cycles of chemotherapy with cisplatin and fluorouracil (weeks 1 and 5). One or two sessions of 5-7 Gy intraluminal high dose-rate brachytherapy were carried out on patients whose restaging showed a major tumor response. Surgery was performed in 14 patients. Results At the end of radiotherapy, dysphagia disappeared in 46/75 cases (61%), and in 20/75 (27%) a significant symptom reduction was recorded. Complete objective response at restaging after radiotherapy was obtained in 33% of patients and a partial response in 53%. At the end of the multimodal treatment program, including esophagectomy, complete responses were 34 (45%); 4 of 14 (28.5%) cases proved to be disease free (pTO) at pathological examination. No G3-G4 toxicity was recorded. Two- and 5-year overall survival rates of all patients were, respectively, 38% and 28%; 2- and 5-year local control rates were, respectively, 35% and 33%. In a subgroup of 20 nonsurgical patients in complete response after radiochemotherapy, the overall survival rate at 3 and 5 years was 65% and the local control rate at 3 and 5 years was 75%. According to multivariate analysis, prognostic factors for survival were Karnofsky index and esophagectomy. Conclusions For patients with locally advanced disease, radiochemotherapy showed improved clinical and pathologic tumor response and survival compared to surgery or radiotherapy alone. Intraluminal brachytherapy with a small fraction size allows an increased dose to the tumor without higher toxicity. Esophagectomy following radiochemotherapy could improve survival rates compared to definitive radiochemotherapy, but it is necessary to optimize selection criteria for surgery at the re-evaluation phase.
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Objective
To investigate the efficacy and toxicity of low dose of docetaxel and cisplatin (TP) combined with radiotherapy in the treatment of elderly patients with esophageal cancer.
Methods
The data of 65 elderly patients with esophageal cancer were studied retrospectively, including 33 patients treated by TP combined with radiotherapy(chemoradiotherapy group) and 32 patients by radiotherapy only (radiotherapy group). Patients in both groups received 3D conventional radiotherapy (3D-CRT). In chemoradiotherapy group, 40 mg/1f docetaxel and 40 mg/1f cisplatin were administered once a week on the 1st, 8th, 15th, 22th, 36th day of five successive weeks.
Results
In chemoradiotherapy group and radiotherapy group, the response (CR+RR) rates were 87.8 % (29/33) and 65.6 % (21/32), respectively (P 0.05). The incidences of esophagitis and gastrointestinal tract were slightly higher in chemoradiotherapy group than those in radiotherapy group (P< 0.05).
Conclusion
Concurrent radiotherapy and chemotherapy with low dose TP can treat effectively esophageal cancer in elderly patients with the tolerable toxic reactions.
Key words:
Esophageal neoplasms; Docetaxel; Cisplatin; Radiotherapy; Elderly
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A 66-year-old patient, who had advanced esophageal cancer with lymph node metastasis, was treated by neoadjuvant chemo-radiotherapy, followed by curative surgery. Chemotherapy of TS-1 (80 mg/m2) was administered orally for 21 days, and weekly intravenous administration of CDDP (20 mg/m2) was done 3 times. Radiotherapy at 2 Gy/day was combined 15 times (total 30 Gy). The tumor responded well to the treatment, and the size was remarkably reduced. Chemoradiotherapy using TS-1 and weekly CDDP revealed their efficacy for esophageal cancer.
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Background. Currently primary treatment options for esophageal cancer are surgery only or concomitant chemoradiotherapy (CRT) and the long-term survival of patients with locally advanced disease is rare. Preoperative concomitant CRT seems to be beneficial, mostly in patients who achieve a complete pathologic response (pCR) after CRT. In this retrospective analysis the efficiency and toxicity of preoperative CRT in patients with locally advanced esophageal cancer was analysed as well as the influence of pCR on the survival. Patients and methods. From 1996 to 2002 41 patients with locoregionally confined esophageal cancer were treated with cisplatin 75 mg/m2 and 5-FU 1000 mg/m2 as 4 day contonuous infusion starting on days 1. and 22. with concomitant radiotherapy 4500 cGy, 200-300 cGy/day. Esophagectomy followed 4-5 weeks after radiotherapy. After the surgery patients were followed-up regularly at 3-6 months intervals. Results. The pCR was achieved in 26.8% of patients. The overall median survival time was 18 months for all patients, 21.2 months for patients who achieved pCR and 16 months in those with residual disease (p= 0,79). Postoperative mortality rate was 22%. The median dose intensity for cisplatin was 92% and for 5-FU 71.5% of the planned dose. Disease recurred most often locoregionally (31.7%) and the overall recurrence rate was 43.9%. Conclusion. Modern radiation techniques and the adequate dose intensity could further improve the locoregional control. The selection of patients without comorbid conditions and without already present distant metastases is essential for this combined treatment approach.
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Surgery remains the standard radical therapy of esophageal cancer. Esophagectomy is accompanied by high proportion of morbidity and mortality, and on overall provides relatively poor results. Recently in esophageal cancer, radiation therapy has been more frequently combined with other modalities including chemotherapy and surgery. Survival benefit following preoperative chemoradiotherapy was demonstrated in only one randomized trial including patients with adenocarcinoma. Similarly, no survival benefit following postoperative chemoradiotherapy was demonstrated. Therefore, such two-modality strategies are not recommended as a standard management. Definitive radiotherapy is indicated in early-stage esophageal cancer patients not amenable to surgery because of comorbid conditions, in those who refused surgery, and in selected patients with locally advanced disease. Improved survival rates, yet at the expense of increased toxicity, were reported by the combining of radiotherapy with chemotherapy including 5-fluorouracil and cisplatin. Both brachytherapy and external beam radiotherapy are the main palliative approaches in patients with dysphagia.
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Esophageal cancer is often diagnosed in its late stages with a 5-year overall survival rate of approximately 28% in British Columbia. It frequently presents as either squamous cell carcinoma or adenocarcinoma. The most common presenting complaint is dysphagia, typically characterized by a worsening tolerance to solid foods. Esophagogastroduodenoscopy with biopsy is the gold standard for diagnosis. CT scan of the chest and abdomen, FDG-PET scan, and endoscopic ultrasound are useful staging investigations. Esophageal cancer is a heterogeneous disease with no single optimal treatment algorithm. Esophagectomy is the preferred treatment modality in Tis-T1 disease. Neoadjuvant chemoradiotherapy prior to definitive surgery should always be considered in T2 disease and is recommended in ≥T3 or N+ disease. There is controversial evidence against the survival benefit and potential added morbidity of neoadjuvant chemoradiotherapy in the treatment of early esophageal cancer. Unresectable and cervical tumors should be treated with definitive chemoradiotherapy. The optimal treatment of adenocarcinomas of the distal esophagus and gastro-esophageal junction is under investigation but likely includes peri-operative chemotherapy. Current research in esophageal cancer includes the use of early FDG-PET scans to assess response to chemotherapy, which could have important implications in prognostication and treatment decisions. Keywords: localized esophageal cancer, management, chemoradiotherapy, FDG-PET
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Objective To compare the short term effectivity, and survival rates of hyperfractionated radiotherapy plus chemotherapy concurrutly with hyperfractionated radiotherapy alone in patients with upper and middle esophageal cancer. Metheds:One hundred and fifty eight patients with upper and middle esophageal cancer were randomized into two groups where 75 treated by chemoradiotherapy(CRT) and 83 by radiotherapy(RT) alone. The chemotherapy included cispatin 20 mg/m 2 on d1 d5 infusion, 5 fluorouracil 500 mg/m 2 on d1 d5 by continuous infusion for 6 8 hours.Hyperfractionated radiotherapy were similar in the two groups:1.3 Gy/f,twice a day.Results 1 , 3 , 5 year suvival rates were 70.7%,40.0% and 24.0% for CRT and 51.8%,21.7%,10.8% for RT, respectively. The difference is statistically significant. The toxic and side effects are tolerable in the two groups. Conclusion Concurrut chemotherapy with 5 fluorouracil, cisplatin combimed hyperfractionated radiotherapy may improve the outcome of esophageal cancer, with the toxic and side effects being tolerated by all patients.
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International guidelines recommend brachytherapy for patients with dysphagia from esophageal cancer, whereas brachytherapy is infrequently used to palliate dysphagia in some countries. To clarify the availability of palliative treatment for dysphagia from esophageal cancer and explain why brachytherapy is not routinely performed are unknown, this study investigated the use of brachytherapy and external beam radiotherapy for dysphagia from esophageal cancer.Japanese Radiation Oncology Study Group members completed a survey and selected the treatment that they would recommend for hypothetical cases of dysphagia from esophageal cancer.Of the 136 invited facilities, 61 completed the survey (44.9%). Four (6.6%) facilities performed brachytherapy of the esophagus, whereas brachytherapy represented the first-line treatment at three (4.9%) facilities. Conversely, external beam radiotherapy alone and chemoradiotherapy were first-line treatments at 61 and 58 (95.1%) facilities, respectively. In facilities that performed brachytherapy, the main reason why brachytherapy of the esophagus was not performed was high invasiveness (30.2%). Definitive-dose chemoradiotherapy with (≥50 Gy) tended to be used in patients with expected long-term survival.Few facilities routinely considered brachytherapy for the treatment of dysphagia from esophageal cancer in Japan. Conversely, most facilities routinely considered external beam radiotherapy. In the future, it will be necessary to optimize external beam radiotherapy.
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