Japanese Journal of Clinical Oncology Advance Access originally published online on July 23, 2007
Japanese Journal of Clinical Oncology 2007 37(7):493-500; doi:10.1093/jjco/hym055
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© 2007 Foundation for Promotion of Cancer Research
Results of the 1999–2001 Japanese Patterns of Care Study for Patients Receiving Definitive Radiation Therapy without Surgery for Esophageal Cancer
1 Department of Radiology, Hiroshima University Graduate School of Medicine, Hiroshima
2 Department of Radiation Oncology, Chiba University Graduate School of Medicine, Chiba
3 Department of Radiation Oncology, The Cancer Institute Hospital, The Japanese Foundation for Cancer Research, Tokyo
4 Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, Osaka, Japan
For reprints and all correspondence: Yuji Murakami, Department of Radiology, Hiroshima University Graduate School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. E-mail: yujimura{at}hiroshima-u.ac.jp
Received October 2, 2006; accepted March 2, 2007
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Abstract |
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 TOP Abstract INTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSConflict of interest statementReferences |
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Background: The third Japanese Patterns of Care Study (JPCS) was conducted for esophageal cancer patients receiving radiotherapy (RT). The aim of this study is to analyse the data of the non-surgery group.
Methods: Of the 621 patients receiving RT from 1999 to 2001, 385 non-surgical patients were analysed.
Results: Median age was 71 years and 85% were male. Karnofsky performance status (KPS) was 
80 in 71% and better in T1 cases than in T2–4 cases. Ninety-nine per cent had squamous cell carcinoma and 56% had the main lesion in the middle thoracic esophagus. Twenty-one per cent had T1 disease, 12% T2, 38% T3 and 29% T4. Endoscopic ultrasound was used in 29% and mainly in T1 cases. Endoscopic mucosal resection was performed in 40% of mucosal cancer. Utilization of chemotherapy had remarkably increased compared with the 1995–1997 JPCS (61% versus 35%), however was significantly less in T1 cases than in T2–4 cases. The most frequently used agents for concurrent use were 5-fluorouracil and cisplatin. The median total dose of external beam RT (ERT) was 60 Gy and did not differ between T1 and T2–4 cases and also in comparison with the 1995–1997 JPCS. Brachytherapy was used in 10% and mainly in T1 cases.
Conclusions: Utilization of chemotherapy had remarkably increased. However the common treatment for T1 cases was RT alone. The standard dose of ERT was 60 Gy in spite of the increase in chemotherapy administration. Moreover, this survey showed significant differences in many parameters of treatment process between T1 and T2–4 cases.
Key Words: Patterns of Care Study • esophageal cancer • radiotherapy • depth of tumor invasion
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INTRODUCTION |
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TOPAbstractINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSConflict of interest statementReferences |
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To improve the quality of radiotherapy (RT), the Patterns of Care Study (PCS) was introduced to Japan from the USA, courtesy of the American College of Radiology in 1996. So far, three Japanese PCS (JPCS) surveys for esophageal cancer patients receiving RT have been performed. The first survey was conducted from 1996 to 1998 collecting data of patients treated from 1992 to 1994. In this 1992–1994 JPCS, the feasibility of JPCS was confirmed and the author concluded that institutional stratification including equipment and personnel had significantly affected the patterns of care for esophageal cancer (1). The second survey was carried out from 1998 to 2001, collecting data of patients treated from 1995 to 1997. The report of this survey emphasized that there had been several problems that needed resolving immediately, such as the use of inappropriate lower photon beam energy and the excess dose applied to the spinal cord (2,3). Moreover, the utilization rate of chemo-radiotherapy (CRT) in this survey was about 40%, and CRT was not established as the standard therapy for cancer of the esophagus during this time period. However, according to the results of the 1996–1999 PCS for esophageal cancer patients in the United States (USPCS) (4), 89% of patients received chemotherapy in addition to RT. The author concluded that this study confirmed the use of concurrent CRT as part of the standard practice for esophageal cancer. In addition, the significant rise in the use of endoscopic ultrasound (EUS) compared to the 1992–1994 USPCS was identified in this report. It was stated that this had been caused by the revision of the American Joint Committee on Cancer (AJCC) staging system from the old 1983 version to the current 1997 version in which T-classification relies on the depth of tumor invasion.
The objectives of this study were to evaluate the 1999–2001 JPCS data for esophageal cancer patients receiving RT without surgery and also to investigate the differences in treatment process according to the depth of tumor invasion.
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METHODS |
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TOPAbstractINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSConflict of interest statementReferences |
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On the basis of the Japanese facility master list of 1999 (5), all radiation therapy facilities, composed of more than 700 institutions, were classified as follows: A1, academic institutions (cancer centers and university hospitals) treating
430 patients a year; A2, <430 patients; B1, other non-academic institutions treating 130 patients a year; and B2, <130 patients. A stratified two-stage cluster sampling was used to select facilities and patients for review (Fig. 1). In the first stage of sampling, facilities were randomly selected for investigation. In the second stage, random sampling of patients was performed from all eligible patients of each facility. Radiation oncologists of the JPCS Working Group, who visited each selected facility and reviewed the records of the selected patients, collected data from 2002 to 2004. For this survey, 76 facilities were selected (20 from A1, 18 from A2, 20 from B1 and 18 from B2). The number of selected facilities corresponds to a little over 10% of all RT facilities in Japan. The inclusion criteria were thoracic and abdominal esophageal cancer treated with RT from 1999 to 2001, squamous cell, adenosquamous cell or adenocarcinoma histology and Karnofsky performance status (KPS) of 60 or more. Patients with distant organ metastasis or other active malignancies within 5 years prior to treatment were excluded. Cervical esophageal cancer patients were excluded because the treatment strategy and the various parameters of RT differ from thoracic and abdominal cancer patients. The clinical data of 621 esophageal cancer patients receiving RT with or without surgery were accumulated. Of these, 385 patients (62%) who received RT without surgery were analysed (106 patients from A1, 88 from A2, 142 from B1 and 49 from B2).
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430 patients a year; A2, <430 patients; B1, other non-academic institutions treating Statistical analyses were performed using the statistical analysis system (SAS) at the JPCS statistical center (6). Statistical significance was tested using the
2 test and Student's t-test. |
RESULTS |
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TOPAbstractINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSConflict of interest statementReferences |
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Patient and Tumor Characteristics
Patient and tumor characteristics are listed in Table 1. The median age was 71 years and 85% of patients were male. Seventy-one per cent had KPS of 80 or more. Fifty-six per cent of patients had the main lesion in the middle thoracic esophagus and 99% had squamous cell carcinoma histology. According to the 1997 International Union Against Cancer (UICC) staging system, 79 patients (21%) had T1 disease, 51 patients (13%) T2 disease, 143 patients (37%) T3 disease and 112 patients (29%) T4 disease. Among the 79 patients with T1 disease, 15 (4%) had mucosal cancer and 64 (17%) had submucosal cancer. Sixteen patients were clinical stage I, 29% were stage II, 43% were stage III and 12% were stage IVa-b. The patient characteristics according to the depth of tumor invasion were shown in Table 2. The KPS of patients with T1 disease was better than patients with T2–4 disease (P = 0.0001).
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Pretreatment Evaluation
Procedures of pretreatment evaluation are shown in Table 3. Ninety-four per cent of patients had an esophagram, and 96% underwent endoscopy. Computed tomography (CT) scans of the chest and abdomen were obtained in 97 and 90%, respectively. There was no significant difference in the use of these procedures according to the depth of tumor invasion. EUS was used in 29%. The utilization rates of EUS for T1, T2, T3 and T4 cases were 53, 29, 21 and 21%, respectively, and T1 cases underwent it more frequently than T2–4 cases (P = 0.0001). Magnetic resonance imaging (MRI) was used on 15% of patients. The performance rates for T1, T2, T3 and T4 cases were 3, 13, 12 and 26%, respectively, and this procedure was performed significantly less in T1 cases than in T2–4 cases (P = 0.0051).
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Treatment
Treatment characteristics are shown in Table 4. Ninety-three per cent of patients were hospitalized for treatment. There was no significant difference in the ratio of hospitalization between T1 and T2–4 cases. Planned treatment was accomplished in 83% of patients. The accomplishment rates for T1, T2, T3 and T4 cases were 94, 78, 82 and 77%, respectively, and the rate for T1 cases was higher than T2–4 cases (P = 0.0441). Endoscopic mucosal resection (EMR) was performed in 15% of T1 cases before RT, and the performance rates for mucosal and submucosal cancer were 40 and 9%, respectively.
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Treatment Strategy
Of all patients, 61% received CRT and 39% received RT alone. The utilization rates of CRT for T1, T2, T3 and T4 cases were 28, 74, 58 and 79%, respectively, and there was a significant difference in the use of CRT between T1 and T2–4 cases (P = 0.0001). Among patients with T1 disease, 20% with mucosal cancer and 30% with submucosal cancer received CRT.
Radiotherapy
All patients included in this study received external beam RT (ERT). The median total dose of ERT was 60 Gy and the median fraction dose was 2 Gy. There was no difference in the median total dose and the median fraction dose of ERT between T1 and T2–4 cases. Regarding irradiation fields (40 Gy), 66% of patients received whole mediastinal irradiation. Nodal irradiation fields (40 Gy) according to the tumor main location were shown in Table 5. Patients with upper thoracic tumors were irradiated supraclavicular region in 53%, whole mediastinal region in 70% and upper abdominal region in 3%. Patients with middle thoracic tumors were irradiated supraclavicular region in 13%, whole mediastinal region in 69% and upper abdominal region in 16%. Patients with lower thoracic tumors were irradiated supraclavicular region in 8%, whole mediastinal region in 49% and upper abdominal region in 35%. Brachytherapy (BT) was used in 10% of patients as a means of boosting the primary tumor site. Seventy-four per cent of patients who received BT were treated by high-dose-rate source and 26% by low-dose-rate source. The performance rates of BT for T1, T2, T3 and T4 cases were 20, 14, 6 and 5%, respectively, and a significant difference in its use was found between T1 and T2–4 cases (P = 0.0018). Among patients with T1 disease, 27% with mucosal cancer and 18% with submucosal cancer received BT.
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Chemotherapy
Chemotherapy was administered in 61% of patients, as mentioned above. Of these, 73% received chemotherapy concurrently with RT, 15% before RT and 12% after RT. The most frequently used individual agents for concurrent CRT cases were 5-fluorouracil (5-FU) (97%) and cisplatin (82%). The patients who were administered the combination of cisplatin and 5-FU concomitantly were 80% of concurrent CRT cases. When the combination of cisplatin and 5-FU was used for concurrent CRT, the administration schedules were daily administration in 64%, tri-weekly/monthly administration in 19%, weekly administration in 14% and others in 4%. There was no use of paclitaxel or docetaxel in this study.
Comparison with the 1995–1997 JPCS
Comparison of work up and process for non-surgical patients between the 1995–1997 JPCS survey and this survey is shown in Table 6. Work up to including age, gender, KPS and histology was almost the same. The administration rate of chemotherapy had remarkably increased (35% versus 61%) and the performance rate of BT had decreased (17% versus 10%). Regarding ERT, the median total dose and fraction dose of ERT did not change and the ratio of whole mediastinal nodal irradiation had increased (47% versus 66%).
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DISCUSSION |
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TOPAbstractINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSConflict of interest statementReferences |
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In this survey, we evaluated the 1999–2001 JPCS data of esophageal cancer patients receiving RT without surgery and revealed significant differences in patterns of care according to the depth of tumor invasion. Among patient characteristics, a KPS of T1 cases was better than T2–4 cases in this survey. This possibly suggests that a ratio that definitive RT/CRT was chosen for operable T1 cases increased. It is thought to be attributable that the RT/CRT has been recognized as a curable treatment for T1 tumors.
In the report of the 1996–1999 USPCS for esophageal cancer, the significant rise in the use of EUS compared to the 1992–1994 USPCS was identified (4). The performance rate of EUS in this JPCS survey was higher than in the 1996–1999 USPCS (29% versus 18%). Furthermore, more than half of T1 cases had EUS and the performance rate was significantly higher in T1 cases than in T2–4 cases. In Japan, there is an original staging system created by the Japanese Society for Esophageal Diseases (7). The particularity of the Japanese staging system is that T1 disease is subclassified into mucosal cancer as T1a and submucosal cancer as T1b. The incidences of lymph node metastasis in mucosal cancer and submucosal cancer were reported as 0–5% and 41.4–53.3%, respectively (8–11), and the survival rate for submucosal cancer is significantly worse than for mucosal cancer (12–14). From this point of view, the diagnosis of mucosal cancer or submucosal cancer is regarded as very important. The accuracy of EUS for the diagnosis of the depth of tumor invasion for esophageal cancer has been reported to be more than 80% (15, 16). The reason why the performance rate of EUS was high in T1 cases was that EUS was thought to be the most useful procedure for the diagnosis of mucosal cancer and submucosal cancer. As a new diagnostic procedure for esophageal cancer, positron emission tomography (PET) has recently been noted. The usefulness of PET for pretreatment staging, especially for detecting lymph node metastases, has been reported (17–20). Although PET was not investigated in this survey, this procedure should be examined in a future study in order to increase its future use.
EMR is effective and the least invasive treatment method for small mucosal cancer. Its local control rate is very high and is equivalent to esophagectomy (21–23). Because of the low rate of lymph node metastasis, additional treatment is not necessary for mucosal cancer after complete resection by EMR. However, in cases with positive margin or deeper invasion identified pathologically, additional treatment should be considered. In this survey, 40% of patients with mucosal cancer and 9% with submucosal cancer received EMR before radiotherapy. Recently, positive outcomes of RT and CRT following EMR have been reported (24,25). Considering the high performance rate of EMR before RT for mucosal cancer in this survey, this combination of treatments should be examined in detail in future.
Compared with the 1995–1997 JPCS, the performance ratio of CRT has remarkably increased. There are potentially several reasons such as the facts that several reports evaluating the efficacy of CRT have been published (26–29) and that the percentage of patients who were eligible for chemotherapy has increased. In spite of the increase in the use of chemotherapy, the most common treatment regimen for T1 cases was still RT alone during this time period. Recently, positive results of CRT for T1 cases have been reported (30,31) which means we need to investigate the transition of CRT for T1 cases in the next study.
Regarding ERT, the median fraction dose and the median total dose were 2 and 60 Gy, respectively, and they were not different between T1 and T2–4 cases. This result suggests that the strength of RT was not weakened for T1 cases in the treatment of esophageal cancer. Furthermore, compared with the 1995–1997 JPCS, the median total dose did not change in spite of the remarkable increase in chemotherapy administration. This suggests that not a small number of the patients receiving CRT were treated by ERT with a dose of 60 Gy. According to the data of the 1996–1999 USPCS, the median total dose of ERT was 50.4 Gy (4). Additionally, the result of the phase III trial of CRT with high dose (64.8 Gy) versus standard dose (50.4 Gy) for esophageal cancer was published in 2002 (32). In this report it is concluded that the higher radiation dose did not increase survival or local/regional control and the standard radiation dose for patients treated with concurrent CRT was 50.4 Gy. The patients in our study were treated in 1999–2001, so we need to compare with the result of the next PCS in order to evaluate the change of irradiation dose after this report. However, when we look at the clinical situation, the result of this trial seems not to be accepted at this moment in Japan.
With the comparison of the ratio of whole mediastinal irradiation between this survey and the 1995–1997 JPCS, irradiation fields became wider. However, from the results of the analysis of irradiation fields according to the tumor main location, it is suggested that the three-field (supraclavicular, whole mediastinal and upper abdominal region) nodal irradiation was rarely used and the localized fields were used at a constant rate. Cardiopulmonary toxicities after CRT have become a topic of interest since the paper by Ishikura et al. (33). These toxicities may be attributable to the usage of chemotherapy and extremely large field such as the so-called ‘super-long-T field’. As it is anticipated that long-term survivors after CRT for esophageal cancer will increase hereafter, investigations of late toxicities including cardiovascular toxicities, the optimum ERT dose and the optimum ERT fields need to be carried out.
The performance ratio of BT was 10% and patients with T1 disease had BT significantly more frequently than those with T2–4 disease. This result suggested that in Japan BT was often used to boost irradiation following ERT for T1 disease rather than for advanced cancer. Compared with the 1995–1997 JPCS, the performance ratio of BT has decreased (17% versus 10%). As a result of the introduction of CRT and use of the 3D-treatment technique, it is thought that there may be a change of direction in the use of BT for esophageal cancer in the future.
Regarding the sequence of chemotherapy administration, concurrent use with RT was the most common for any depth of tumor invasion. Cisplatin and 5-fluorouracil were the most frequently used agents in concurrent CRT. Evidence of the effectiveness of the combination of cisplatin and 5-fluorouracil has been shown for cancer of the esophagus (26–29), and it is thought that this has affected the choice of agents. However, as for the dosage method, daily low-dose administration was used most commonly without enough evidence. The evaluation of this method is entrusted to the future. Although the use of taxane has remarkably increased recently in the USA (4), this agent was not used at all during the time period in this survey. However, as docetaxel was covered by health insurance for esophageal cancer from 2004 in Japan, it is predicted that its use will increase in future.
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CONCLUSIONS |
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TOPAbstractINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSConflict of interest statementReferences |
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We evaluated the 1999–2001 JPCS data for non-surgical esophageal cancer patients. The performance rate of CRT had remarkably increased compared with the 1995–1997 JPCS survey. However the common treatment for T1 cases was still RT alone. The standard dose of ERT was 60 Gy in spite of the remarkable increase in chemotherapy administration. Moreover, this survey showed significant differences in many parameters of work up and treatment process between T1 and T2–4 cases.
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Conflict of interest statement |
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TOPAbstractINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSConflict of interest statementReferences |
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None declared.
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Acknowledgments |
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We would like to thank all radiation oncologists who participated in this study for their support and cooperation. This paper was supported by a Grant-in-Aid for Cancer Research (No. 14-6) from the Ministry of Health, Labor and Welfare of Japan and a Grant from the Japan Society for the Promotion of Science.
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References |
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TOPAbstractINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSConflict of interest statementReferences |
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1 Teshima T, Abe M, Ikeda H, Hanks GE, Owen JB, Hiraoka M, et al. Patterns of care study of radiation therapy for esophageal cancer in Japan: influence of the stratification of institution on the process. Jpn J Clin Oncol (1998) 28:308–13.
2 Gomi K, Oguchi M, Hirokawa Y, Kenjo M, Ogata T, Takahashi Y, et al. Process and preliminary outcome of a patterns-of-care study of esophageal cancer in Japan: patients treated with surgery and radiotherapy. Int J Radiat Oncol Biol Phys (2003) 56:813–22.[CrossRef][Web of Science][Medline]
3 Kenjo M, Oguchi M, Gomi K, Yamashita T, Uno T, Hirokawa Y, et al. Radiation therapy for esophageal cancer: results of the patterns of care study in Japan. Esophagus (2005) 2:77–83.[CrossRef]
4 Suntharalingam M, Moughan J, Coia LR, Krasna MJ, Kachnic L, Haller DG, et al. The national practice for patients receiving radiation therapy for carcinoma of the esophagus: results of the 1996–1999 Patterns of Care Study. Int J Radiat Oncol Biol Phys (2003) 56:981–7.[CrossRef][Web of Science][Medline]
5 JASTRO Database Committee. Present status of radiotherapy in Japan—the regular structure survey in 1999. J Jpn Soc Ther Radiol Oncol (2001) 13:227–35.
6 SAS Procedure Reference Vers. 6. (1995) 1st edn. Tokyo: SAS Institute.
7 Japanese Society for Esophageal Disease. Guidelines for Clinical and Pathologic Studies on Carcinoma of the Esophagus (in Japanese), (1999) 9th edn. Tokyo: Kanehara Shuppan.
8 Nishimaki T, Tanaka O, Suzuki T, Aizawa K, Watanabe H, Muto T. Tumor spread in superficial esophageal cancer: histopathologic basis for rational surgical treatment. Word J Surg (1993) 17:766–72.[CrossRef]
9 Tajima Y, Nakanishi Y, Ochiai A, Tachimori Y, Kato H, Watanabe H, et al. Histopathologic findings predicting lymph node metastasis and prognosis of patients with superficial esophageal carcinoma: analysis of 240 surgically resected tumors. Cancer (2000) 88:1285–93.[CrossRef][Web of Science][Medline]
10 Endo M, Kawano T. Detection and classification of early squamous cell esophageal cancer. Dis Esophagus (1997) 10:155–8.[Medline]
11 Tachibana M, Yoshimura H, Kinugasa S, Hashimoto N, Dhar DK, Abe S, et al. Clinicopathological features of superficial squamous cell carcinoma of the esophagus. Am J Surg (1997) 174:49–53.[CrossRef][Web of Science][Medline]
12 Sugimachi K, Ikebe M, Kitamura K, Toh Y, Matsuda H, Kuwano H. Long-term results of esophagectomy for early esophageal carcinoma. Hepatogastroenterology (1993) 40:203–206.[Medline]
13 Kato H, Tachimori Y, Watanabe H, Yamaguchi H, Ishikawa T, Itabashi M. Superficial esophageal carcinoma. Surgical treatment and the results. Cancer (1990) 66:2319–23.[CrossRef][Web of Science][Medline]
14 Nemoto K, Yamada S, Hareyama M, Nagakura H, Hirokawa Y. Radiation therapy for superficial esophageal cancer: a comparison of radiotherapy methods. Int J Radiat Oncol Biol Phys (2001) 50:639–44.[CrossRef][Web of Science][Medline]
15 Lightdale CJ, Kulkarni KG. Role of endoscopic ultrasonography in the staging and follow-up of esophageal cancer. J Clin Oncol (2005) 23:4483–9.
16 Rice TW, Blackstone EH, Adelstein DJ, Zuccaro G Jr, Vargo JJ, Goldblum JR, et al. Role of clinically determined depth of tumor invasion in the treatment of esophageal carcinoma. J Thorac Cardiovasc Surg (2003) 125:1091–102.
17 Flamen P, Lerut A, Van Cutsem E, De Wever W, Peeters M, Stroobants S, et al. Utility of positron emission tomography for the staging of patients with potentially operable esophageal carcinoma. J Clin Oncol (2000) 18:3202–10.
18 Vrieze O, Haustermans K, De Wever W, Lerut T, Van Cutsem E, Ectors N, et al. Is there a role for FGD-PET in radiotherapy planning in esophageal carcinoma? Radiother Oncol (2004) 73:269–75.[CrossRef][Web of Science][Medline]
19 Kato H, Kuwano H, Nakajima M, Miyazaki T, Yoshikawa M, Ojima H, et al. Comparison between positron emission tomography and computed tomography in the use of the assessment of esophageal carcinoma. Cancer (2002) 94:921–8.[CrossRef][Web of Science][Medline]
20 Yoon YC, Lee KS, Shim YM, Kim BT, Kim K, Kim TS. Metastasis to regional lymph nodes in patients with esophageal squamous cell carcinoma: CT versus FDG PET for presurgical detection prospective study. Radiology (2003) 227:764–70.
21 Shimizu Y, Tsukagoshi H, Fujita M, Hosokawa M, Kato M, Asaka M. Long-term outcome after endoscopic mucosal resection in patients with esophageal squamous cell carcinoma invading the muscularis mucosae or deeper. Gastrointest Endosc (2002) 56:387–90.[CrossRef][Web of Science][Medline]
22 Kodama M, Kakegawa T. Treatment of superficial cancer of the esophagus: a summary of responses to a questionnaire on superficial cancer of the esophagus in Japan. Surgery (1998) 123:432–9.[Web of Science][Medline]
23 Pech O, Gossner L, May A, Vieth M, Stolte M, Ell C. Endoscopic resection of superficial esophageal squamous cell carcinomas: Western experience. Am J Gastroenterol (2004) 99:1226–32.[CrossRef][Web of Science][Medline]
24 Nemoto K, Takai K, Ogawa Y, Sakayauchi T, Sugawara T, Jingu K, et al. Salvage radiation therapy for residual superficial esophageal cancer after endoscopic mucosal resection. Int J Radiat Oncol Biol Phys (2005) 63:1290–4.[CrossRef][Web of Science][Medline]
25 Shimizu Y, Kato M, Yamamoto J, Nakagawa S, Tsukagoshi H, Fujita M, et al. EMR combined with chemoradiotherapy: a novel treatment for superficial esophageal squamous-cell carcinoma. Gastrointest Endosc (2004) 59:199–204.[CrossRef][Web of Science][Medline]
26 Cooper JS, Guo MD, Herskovic A, Macdonald JS, Martenson JA, Al-Sarraf M, et al. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA (1999) 281:1623–7.
27 Al-Sarraf M, Martz K, Herskovic A, Leichman L, Brindle JS, Vaitkevicius VK, et al. Progress report of combined chemoradiotherapy versus radiotherapy alone in patients with esophageal cancer: an intergroup study. J Clin Oncol (1997) 15:277–84.
28 Herskovic A, Martz K, al-Sarraf M, Leichman L, Brindle J, Vaitkevicius V, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med (1992) 326:1593–8.[Abstract]
29 Ohtsu A, Boku N, Muro K, Chin K, Muto M, Yoshida S, et al. Definitive chemoradiotherapy for T4 and/or M1 lymph node squamous cell carcinoma of the esophagus. J Clin Oncol (1999) 17:2915–21.
30 Yamada K, Murakami M, Okamoto Y, Okuno Y, Nakajima T, Kusumi F, et al. Treatment results of chemoradiotherapy for clinical stage I (T1N0M0) esophageal carcinoma. Int J Radiat Oncol Biol Phys (2006) 15:1106–11.
31 Kato H, Udagawa H, Togo A, Ando N, Tanaka O, Shinoda M, et al. A phase II trial of chemo-radiotherapy in patients with stage I esophageal squamous cell carcinoma: Japan Clinical Oncology Group study (JCOG9708). Proc Am Soc Clin Oncol (2003) 22:286.
32 Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, et al. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol (2002) 20:1167–74.
33 Ishikura S, Nihei K, Ohtsu A, Boku N, Hironaka S, Mera K, et al. Long-term toxicity after definitive chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus. J Clin Oncol (2003) 21:2697–702.
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