Definitive Chemoradiation in Esophageal Cancer Patients
Definitive Chemoradiation in Esophageal Cancer Patients
In this multicenter retrospective study, we analyzed 102 EC patients without distant metastases, who were treated with curatively intended dCRT in five centers in the Northeast Netherlands from 1996 till 2008. This subgroup of patients treated with only chemoradiation as definitive treatment is part of a larger cohort described elsewhere. As described in the publication of Smit et al., the indications in both dCRT regimens were technically unresectable tumors, medically unfit patients or patient's own choice. Carboplatin/paclitaxel was the standard regimen in two of the five centers and also preferred above cisplatinum/5-FU for patients with cardiovascular comorbidity. Patients with other histology than adenocarcinoma or squamous carcinoma were excluded as well as cases with missing relevant staging information or inadequate follow-up.
pretreatment staging Pretreatment staging consisted of endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes, 16–64 multidetector computed tomography (md-CT) scans of the neck, chest and abdomen and on indication cervical echographic examination. From 2002 onward, F-fluorodeoxyglucose positron emission tomography (FDG-PET) was added to the staging procedure. Bronchoscopy was required when the tumor was tethered to the trachea or main stem bronchus. Patients were staged according to the Union for International Cancer Control TNM 6th edition.
chemotherapy regimens The cisplatinum/5-FU dCRT (N = 47) regimen consisted of cisplatinum 75 mg/m (day 1) and 5-FU 1 g/m (day 1–4) at week 1 and 5 during RT, with two additional courses on week 8 and 11 (RTOG 85-01 scheme).
In the carboplatin/paclitaxel group (N = 55), a chemotherapy scheme was given weekly during RT at day 1, 8, 15, 22, 29 (and 35). The paclitaxel dose was 50 mg/m and carboplatin was administered at AUC2.
radiation scheme RT planning was carried out after direct simulation, based on diagnostic images or 3D based on treatment planning CT images. During direct simulation, patients had to swallow barium contrast to facilitate identification and localization of the primary tumor. For the planning CT, the patients also received oral contrast.
Gross tumor volume (GTV), defined as the macroscopic primary tumor and regional lymph node metastases, was reconstructed using all available information derived from endoscopy, EUS, CT and from FDG-PET.
At direct simulation, margins from GTV to field margin were 5 cm in caudal/cranial direction and 2 cm margin in transversal plane. A margin of 4 cm in caudal/cranial direction and 1.5 cm in transversal plane was used to generate the planning target volume. If the treatment planning was based on a planning CT, the clinical target volume was obtained by adding a 3-cm margin in cranial–caudal direction and 1 cm margin in transversal plane. A 0.5–1 cm margin was used around pathological lymph nodes.
A total radiation dose of 46.8–70 Gy (median dose 50.4 Gy) was given in daily fractions of 1.8–2 Gy. One patient received a dose of 41.1 Gy as the initial neoadjuvant treatment was switched to dCRT. Generally delivered with at least 6 MV photons. Intraluminal brachytherapy was given in two fractions of 6 Gy or a single fraction of 10 Gy and administered in 5% of the patients.
data acquisition Data was obtained using the medical records of the different centers in the North-East region of the Netherlands. Additional information from comprehensive cancer centers was acquired. The study was carried out according to national ethics guidelines (http://www.ccmo-online.nl).
follow-up Patients were generally seen for regular follow-up according to national guidelines at 4–8 weeks after completion of treatment, every 6 months in the first year and thereafter annually up to 5 years or until death.
toxicity Toxicity was measured according to the Common Terminology Criteria for Adverse Events (CTCAE 4.0). Grade 3 and 4 toxicity reactions are shown in Table 3. Grade 5 toxicity occurring up to 30 days after treatment was recorded as mortality.
statistics OS was defined as the time interval between the starting date of the chemoradiation and documentation of the day of death or last follow-up. Disease-free survival (DFS) was determined from the starting date of treatment to documented date of first recurrence or death of any cause. OS and DFS rates were calculated according to the Kaplan–Meier method and compared using the log-rank test. Patient characteristics and toxicity rates were determined and compared using Student's t-test and Fisher's exact test. Univariate and multivariate analyses were carried out using Cox-regression analyses. P values of <0.150 in the univariate analysis were included in the multivariate analysis. A P value of <0.05 [95% confidence interval (CI)] was considered as significant. The statistical analyses were carried out by using the Statistical Package for Social Sciences (SPSS, Chicago, IL) version 18.0 software.
Patients and Methods
Patients
In this multicenter retrospective study, we analyzed 102 EC patients without distant metastases, who were treated with curatively intended dCRT in five centers in the Northeast Netherlands from 1996 till 2008. This subgroup of patients treated with only chemoradiation as definitive treatment is part of a larger cohort described elsewhere. As described in the publication of Smit et al., the indications in both dCRT regimens were technically unresectable tumors, medically unfit patients or patient's own choice. Carboplatin/paclitaxel was the standard regimen in two of the five centers and also preferred above cisplatinum/5-FU for patients with cardiovascular comorbidity. Patients with other histology than adenocarcinoma or squamous carcinoma were excluded as well as cases with missing relevant staging information or inadequate follow-up.
Methods
pretreatment staging Pretreatment staging consisted of endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes, 16–64 multidetector computed tomography (md-CT) scans of the neck, chest and abdomen and on indication cervical echographic examination. From 2002 onward, F-fluorodeoxyglucose positron emission tomography (FDG-PET) was added to the staging procedure. Bronchoscopy was required when the tumor was tethered to the trachea or main stem bronchus. Patients were staged according to the Union for International Cancer Control TNM 6th edition.
chemotherapy regimens The cisplatinum/5-FU dCRT (N = 47) regimen consisted of cisplatinum 75 mg/m (day 1) and 5-FU 1 g/m (day 1–4) at week 1 and 5 during RT, with two additional courses on week 8 and 11 (RTOG 85-01 scheme).
In the carboplatin/paclitaxel group (N = 55), a chemotherapy scheme was given weekly during RT at day 1, 8, 15, 22, 29 (and 35). The paclitaxel dose was 50 mg/m and carboplatin was administered at AUC2.
radiation scheme RT planning was carried out after direct simulation, based on diagnostic images or 3D based on treatment planning CT images. During direct simulation, patients had to swallow barium contrast to facilitate identification and localization of the primary tumor. For the planning CT, the patients also received oral contrast.
Gross tumor volume (GTV), defined as the macroscopic primary tumor and regional lymph node metastases, was reconstructed using all available information derived from endoscopy, EUS, CT and from FDG-PET.
At direct simulation, margins from GTV to field margin were 5 cm in caudal/cranial direction and 2 cm margin in transversal plane. A margin of 4 cm in caudal/cranial direction and 1.5 cm in transversal plane was used to generate the planning target volume. If the treatment planning was based on a planning CT, the clinical target volume was obtained by adding a 3-cm margin in cranial–caudal direction and 1 cm margin in transversal plane. A 0.5–1 cm margin was used around pathological lymph nodes.
A total radiation dose of 46.8–70 Gy (median dose 50.4 Gy) was given in daily fractions of 1.8–2 Gy. One patient received a dose of 41.1 Gy as the initial neoadjuvant treatment was switched to dCRT. Generally delivered with at least 6 MV photons. Intraluminal brachytherapy was given in two fractions of 6 Gy or a single fraction of 10 Gy and administered in 5% of the patients.
data acquisition Data was obtained using the medical records of the different centers in the North-East region of the Netherlands. Additional information from comprehensive cancer centers was acquired. The study was carried out according to national ethics guidelines (http://www.ccmo-online.nl).
follow-up Patients were generally seen for regular follow-up according to national guidelines at 4–8 weeks after completion of treatment, every 6 months in the first year and thereafter annually up to 5 years or until death.
toxicity Toxicity was measured according to the Common Terminology Criteria for Adverse Events (CTCAE 4.0). Grade 3 and 4 toxicity reactions are shown in Table 3. Grade 5 toxicity occurring up to 30 days after treatment was recorded as mortality.
statistics OS was defined as the time interval between the starting date of the chemoradiation and documentation of the day of death or last follow-up. Disease-free survival (DFS) was determined from the starting date of treatment to documented date of first recurrence or death of any cause. OS and DFS rates were calculated according to the Kaplan–Meier method and compared using the log-rank test. Patient characteristics and toxicity rates were determined and compared using Student's t-test and Fisher's exact test. Univariate and multivariate analyses were carried out using Cox-regression analyses. P values of <0.150 in the univariate analysis were included in the multivariate analysis. A P value of <0.05 [95% confidence interval (CI)] was considered as significant. The statistical analyses were carried out by using the Statistical Package for Social Sciences (SPSS, Chicago, IL) version 18.0 software.
Source...