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The treatment result of definitive radiotherapy for superficial esophageal cancer
264
I. J. Radiation Oncology
2076
● Biology ● Physics
Volume 51, Number 3, Supplement 1, 2001
The Treatment Result of Definitive Radiotherapy for Superficial Esophageal Cancer
K. Seki, K. Karasawa, M. Kohno, N. Hanyuu, M. Isobe, N. Mitsuhashi Radiology, Tokyo Women’s Medical University, Tokyo, Japan Purpose: To assess the effectiveness of radiotherapy and to determine the standard treatment method in patient with superficial esophageal cancer, we analyzed the treatment results of our institute. Materials and Methods: Between 1985 to 2000, 66 patients (62 males, 4 females) with superficial esophageal cancer were treated with radical radiotherapy. The mean age was 66 years old (ranged 42-87). All the cases were confirmed to have squamous cell carcinoma. Fifty-three patients (80.3%) were diagnosed incidentally without any subjective signs. Primary tumor thickness were assessed by endoscopic ultrasonography (EUS) and endoscopy in 50 patients, by endoscopy alone in 16. Depth of tumor invasion were intraepithelial or mucosal tumor in 10 patients, submucosal in 53 and unclassified in 3. Fifty-one patients (77.2%) were without nodal invasion, 15 patients were with nodal invasion. The mean tumor length was 4.9 ⫾ 3.1 cm (ranged 0.7-15.0). Tumor location was cervical esophagus in 7 cases, upper thoracic in 7, middle thoracic in 43, lower thoracic in 7 and superspread in 2. Twenty-one patients had undergone endoscopic treatment (endoscopic mucosal resection (EMR) and/or laser treatment) before radiotherapy. All patients underwent external radiotherapy (EX), 14 were treated with intraluminal radiotherapy (IL) plus EX. The mean total dose was 65.3 ⫾ 6.9 Gy(ranged 38.2-75.6). Thirty-three patients underwent chemotherapy (neoadjuvant chemo therapy in 15, concurrent in 7, adjuvant in 11) with platinums and/or fluorouracils. Median treatment period was 48 days (ranged 30-62). Mean follow-up time was 3.7 ⫾ 2.7 years (ranged 0.17-12.4). Results: Complete response (CR) rate was 82%(54/66) and tumor response (CR⫹partial response) rate was 91%(60/66). Mild (lower than NIC grade 2) esophagitis was observed in 41%(27/39) as early adversed effect. One patient died from radiation pneumonitis. Late complications were seen in 8 patients, two of them underwent operation due to severe painful esophageal ulcer and the others had mild esophageal disconfort including stenosis and prolonged esophagitis. At April 2001, 28 patients survive without the disease, 7 are survival with cancer, 11 died from cancer, 20 died from other diseases. Tumor recurrence were observed in 18 patients (27%), esophagus only in 10, lymph node (LN) only in 2, esophagus⫹LN in 4, LN⫹liver in 1 and bone in 1. Recurrences inside of the radiation field in 11 cases, outside in 5 and inside⫹outside in 2. Overall and cause-specific five-year survival rates were 51.7% and 78.1%, respectively. No statistic significant differences were proved about depth of cancer invasion, tumor length, radiation method, total dose, chemotherapy and endoscopic treatment. Five-year cause-specific survival rates depend on radiation treatment period, less than 48 days were 90.3% and that of more than 49 days were 68.0% (p⫽0.023). Less than 48 days group contained only 1 (/33) case of radiation rest period more than 7 days, while more than 49 days group included 11 (/33) cases of that. There was no significant difference between the two groups about total radiation dose, dose per fraction and performance of chemotherapy. Conclusion: Radiotherapy for superficial esophageal cancer is useful. Five-year cause-specific survival was 78.1% and adverse effect was acceptable. This study indicates that total radiation treatment period should be shortened to achieve good outcome.
2077
A Prospective Randomized Trial of HDR Brachytherapy as a Sole Modality in Palliation of Advanced Esophageal Carcinoma - An International Atomic Energy Agency (IAEA) Study
R.K. Sur1, C.V. Levin2, V. Sharma3, B. Donde1, L. Miszczyk4, S. Nag5 1
Radiation Oncology, University of the Witwatersrand, Johannesburg, South Africa, 2ARBR, IAEA, Vienna, Austria, Radiation Oncology, Tata Memorial Hospital, Mumbai, India, 4Radiation Oncology, Insitute of Oncology, Gliwice, Poland, 5Radiation Oncology, Ohio State University, Columbus, OH 3
Background: Previous studies from South Africa have established that fractionated HDR brachytherapy gives best results in terms of palliation and survival in advanced esophageal cancer. A multi-center, prospective randomized study was therefore conducted to evaluate two HDR regimens. Material and Methods: Surgically inoperable patients with histologically proven squamous cell cancer of the esophagus, tumor ⬎ 5 cm in length on barium swallow and/or endoscopy, Karnofsky performance score ⬎ 50, age 17-70 years, with primary disease in the thoracic esophagus, no prior malignancy within the last 5 years, and any N or M status were included in the study. Exclusion criteria included, cervical esophagus location, tumor extending ⬍ 1 cm from GE junction, tracheoesophageal fistula, Karnofsky performance score ⬍ 50, altered mental status, and extension to great vessels on CT scan. Patients were randomized to receive 18 Gy/3 fractions/alternate days (6 Gy per fraction – Group (Gr) A) or 16 Gy/2 fractions/alternate days (8 Gy per fraction – Gr B). HDR dose was prescribed at 1 cm from the center of the source axis, after dose optimization. A margin of 2 cm was included proximally and distally. Approval for the study was obtained from respective Hospital and University committees and informed consent was obtained in all patients. Results: Two hundred and thirty two patients were entered into the study done under the auspices of the IAEA (112 –Gr A; 120 – Gr B). There was no difference between the groups for any of the prognostic variables. All patients were followed up until death. The dysphagia-free survival for the whole group was 7.1 months (mo) (Gr A⫽7.8 mo, Gr B⫽6.3 mo, p⬎0.05). The overall survival was 7.9 mo for the whole group (Gr A⫽9.1 mo, Gr B⫽6.9 mo, p⬎0.05). On univariate analysis, sex (p⫽0.0038), race (p⫽0.0105), grade (p⫽0.0029), presenting weight (p⫽0.0083), and treatment center (p⫽0.0029) had an impact on dysphagia-free survival, while age (p⫽0.0011) and Karnofsky performance score (p⫽0.0119) had an impact on overall survival on multivariate analysis. Only age had an impact on overall survival on both univariate (p⫽0.0430) and multivariate (p⫽0.0331) analysis. The incidence of strictures (Gr A⫽12, Gr B⫽13, p⬎0.05) and fistulae (Gr A⫽11, Gr B⫽12, p⬎0.05) was similar in both groups. Conclusions: Fractionated HDR brachytherapy alone is an effective method of palliating advanced esophageal cancers surpassing the results of any other modality of treatment presently available. Dose fractions of 6 Gy x 3 and 8 Gy x 2 give similar results for dysphagia-free survival, overall survival, strictures and fistulae.
I. J. Radiation Oncology
2076
● Biology ● Physics
Volume 51, Number 3, Supplement 1, 2001
The Treatment Result of Definitive Radiotherapy for Superficial Esophageal Cancer
K. Seki, K. Karasawa, M. Kohno, N. Hanyuu, M. Isobe, N. Mitsuhashi Radiology, Tokyo Women’s Medical University, Tokyo, Japan Purpose: To assess the effectiveness of radiotherapy and to determine the standard treatment method in patient with superficial esophageal cancer, we analyzed the treatment results of our institute. Materials and Methods: Between 1985 to 2000, 66 patients (62 males, 4 females) with superficial esophageal cancer were treated with radical radiotherapy. The mean age was 66 years old (ranged 42-87). All the cases were confirmed to have squamous cell carcinoma. Fifty-three patients (80.3%) were diagnosed incidentally without any subjective signs. Primary tumor thickness were assessed by endoscopic ultrasonography (EUS) and endoscopy in 50 patients, by endoscopy alone in 16. Depth of tumor invasion were intraepithelial or mucosal tumor in 10 patients, submucosal in 53 and unclassified in 3. Fifty-one patients (77.2%) were without nodal invasion, 15 patients were with nodal invasion. The mean tumor length was 4.9 ⫾ 3.1 cm (ranged 0.7-15.0). Tumor location was cervical esophagus in 7 cases, upper thoracic in 7, middle thoracic in 43, lower thoracic in 7 and superspread in 2. Twenty-one patients had undergone endoscopic treatment (endoscopic mucosal resection (EMR) and/or laser treatment) before radiotherapy. All patients underwent external radiotherapy (EX), 14 were treated with intraluminal radiotherapy (IL) plus EX. The mean total dose was 65.3 ⫾ 6.9 Gy(ranged 38.2-75.6). Thirty-three patients underwent chemotherapy (neoadjuvant chemo therapy in 15, concurrent in 7, adjuvant in 11) with platinums and/or fluorouracils. Median treatment period was 48 days (ranged 30-62). Mean follow-up time was 3.7 ⫾ 2.7 years (ranged 0.17-12.4). Results: Complete response (CR) rate was 82%(54/66) and tumor response (CR⫹partial response) rate was 91%(60/66). Mild (lower than NIC grade 2) esophagitis was observed in 41%(27/39) as early adversed effect. One patient died from radiation pneumonitis. Late complications were seen in 8 patients, two of them underwent operation due to severe painful esophageal ulcer and the others had mild esophageal disconfort including stenosis and prolonged esophagitis. At April 2001, 28 patients survive without the disease, 7 are survival with cancer, 11 died from cancer, 20 died from other diseases. Tumor recurrence were observed in 18 patients (27%), esophagus only in 10, lymph node (LN) only in 2, esophagus⫹LN in 4, LN⫹liver in 1 and bone in 1. Recurrences inside of the radiation field in 11 cases, outside in 5 and inside⫹outside in 2. Overall and cause-specific five-year survival rates were 51.7% and 78.1%, respectively. No statistic significant differences were proved about depth of cancer invasion, tumor length, radiation method, total dose, chemotherapy and endoscopic treatment. Five-year cause-specific survival rates depend on radiation treatment period, less than 48 days were 90.3% and that of more than 49 days were 68.0% (p⫽0.023). Less than 48 days group contained only 1 (/33) case of radiation rest period more than 7 days, while more than 49 days group included 11 (/33) cases of that. There was no significant difference between the two groups about total radiation dose, dose per fraction and performance of chemotherapy. Conclusion: Radiotherapy for superficial esophageal cancer is useful. Five-year cause-specific survival was 78.1% and adverse effect was acceptable. This study indicates that total radiation treatment period should be shortened to achieve good outcome.
2077
A Prospective Randomized Trial of HDR Brachytherapy as a Sole Modality in Palliation of Advanced Esophageal Carcinoma - An International Atomic Energy Agency (IAEA) Study
R.K. Sur1, C.V. Levin2, V. Sharma3, B. Donde1, L. Miszczyk4, S. Nag5 1
Radiation Oncology, University of the Witwatersrand, Johannesburg, South Africa, 2ARBR, IAEA, Vienna, Austria, Radiation Oncology, Tata Memorial Hospital, Mumbai, India, 4Radiation Oncology, Insitute of Oncology, Gliwice, Poland, 5Radiation Oncology, Ohio State University, Columbus, OH 3
Background: Previous studies from South Africa have established that fractionated HDR brachytherapy gives best results in terms of palliation and survival in advanced esophageal cancer. A multi-center, prospective randomized study was therefore conducted to evaluate two HDR regimens. Material and Methods: Surgically inoperable patients with histologically proven squamous cell cancer of the esophagus, tumor ⬎ 5 cm in length on barium swallow and/or endoscopy, Karnofsky performance score ⬎ 50, age 17-70 years, with primary disease in the thoracic esophagus, no prior malignancy within the last 5 years, and any N or M status were included in the study. Exclusion criteria included, cervical esophagus location, tumor extending ⬍ 1 cm from GE junction, tracheoesophageal fistula, Karnofsky performance score ⬍ 50, altered mental status, and extension to great vessels on CT scan. Patients were randomized to receive 18 Gy/3 fractions/alternate days (6 Gy per fraction – Group (Gr) A) or 16 Gy/2 fractions/alternate days (8 Gy per fraction – Gr B). HDR dose was prescribed at 1 cm from the center of the source axis, after dose optimization. A margin of 2 cm was included proximally and distally. Approval for the study was obtained from respective Hospital and University committees and informed consent was obtained in all patients. Results: Two hundred and thirty two patients were entered into the study done under the auspices of the IAEA (112 –Gr A; 120 – Gr B). There was no difference between the groups for any of the prognostic variables. All patients were followed up until death. The dysphagia-free survival for the whole group was 7.1 months (mo) (Gr A⫽7.8 mo, Gr B⫽6.3 mo, p⬎0.05). The overall survival was 7.9 mo for the whole group (Gr A⫽9.1 mo, Gr B⫽6.9 mo, p⬎0.05). On univariate analysis, sex (p⫽0.0038), race (p⫽0.0105), grade (p⫽0.0029), presenting weight (p⫽0.0083), and treatment center (p⫽0.0029) had an impact on dysphagia-free survival, while age (p⫽0.0011) and Karnofsky performance score (p⫽0.0119) had an impact on overall survival on multivariate analysis. Only age had an impact on overall survival on both univariate (p⫽0.0430) and multivariate (p⫽0.0331) analysis. The incidence of strictures (Gr A⫽12, Gr B⫽13, p⬎0.05) and fistulae (Gr A⫽11, Gr B⫽12, p⬎0.05) was similar in both groups. Conclusions: Fractionated HDR brachytherapy alone is an effective method of palliating advanced esophageal cancers surpassing the results of any other modality of treatment presently available. Dose fractions of 6 Gy x 3 and 8 Gy x 2 give similar results for dysphagia-free survival, overall survival, strictures and fistulae.