Japanese Journal of Clinical Oncology 33:456-462 (2003)
© 2003 Foundation for Promotion of Cancer Research
Patterns of Care Study in Japan: Analysis of Patients Subjected to Mastectomy Followed by Radiotherapy
1 Japanese PCS Working Subgroup of Breast Cancer, 2 Department of Radiology, Shinshu University, School of Medicine, Matsumoto, Nagano, 3 Department of Radiation Oncology, Kyoto University School of Medicine, Kyoto, 4 Department of Medical Engineering, Osaka University Faculty of Medicine, Osaka and 5 Division of Multidisciplinary Radiotherapy, The Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONSACKNOWLEDGMENTSREFERENCES |
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Background: Two prospective studies reported in 1997 demonstrated that postoperative radiotherapy after mastectomy was not only associated with a higher loco-regional control rate but also with a higher overall survival rate. The purpose of this study is to clarify the processes of care for patients undergoing mastectomy and postoperative radiotherapy in Japan.
Methods: A national survey carried out in 1998–2000, involving 79 Japanese institutions by two-stage cluster sampling of institutions and patients, disclosed that 1124 patients with breast cancer had been treated between 1995 and 1997. Mastectomy followed by radiotherapy was performed on 258 patients.
Results: The compliance rates for pre-treatment evaluation, including history, physical examination and mammography, averaged ~50% (24–81%). The chest wall was irradiated in only 19% of the patients and regional node irradiation was carried out for 70–86%. Radiation treatment planning with the aid of computed tomography was done in only 29% of patients (university hospitals or cancer centers, 39%; other hospitals, 17%; P = 0.001). Hormonal therapy was administered to 56% of the patients who showed no endocrine responsiveness. Non-intensive chemotherapy, which did not include the use of anthracycline or taxol, was used in 55% of the patients who received chemotherapy.
Conclusions: There is room for improvement regarding some aspects of radiotherapy and adjuvant systemic therapies. Especially in the field of radiotherapy, significant differences were found among the treatment techniques employed in various institutions.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONSACKNOWLEDGMENTSREFERENCES |
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Several differences exist between the United States and Japan with regard to medical care systems and cancer treatment including structure, staff-pattern and processes of care (1). Sophisticated structure and process for cancer treatment may lead to a good treatment outcome (2). Teshima et al. reported that there were big differences in the structure and staff-pattern of radiation oncology between the United States and Japan (1). The ratio of radiation oncologists to population in the United States was three times that in Japan. One-half of the newly diagnosed patients with cancer were treated with radiotherapy in the United States, whereas only 15% of the newly diagnosed patients were treated in Japan (1). A severe shortage of manpower in the field of radiation oncology, including radiation oncologists, medical physicists and dosimetrists, may prevent improvement of the structure.
A comprehensive multidisciplinary approach is crucial for patients with breast cancer, which consists of loco-regional therapy in the case of patients with locally advanced breast cancer, such as surgical management and postoperative radiotherapy, and systemic therapy such as chemotherapy and hormonal therapy (3). The consensus meeting held in St Gallen and other guidelines recommended an adequate adjuvant therapy in relation to the risk factors (4–6). Clarification on the present status of the therapeutic process in Japan is important to establish a multidisciplinary approach for patients subjected to mastectomy and postoperative radiotherapy.
This study was undertaken to clarify the therapeutic process including work-up, surgery, radiotherapy, chemotherapy and hormonal therapy for patients subjected to mastectomy and postoperative radiotherapy in Japan.
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PATIENTS AND METHODS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONSACKNOWLEDGMENTSREFERENCES |
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A national survey carried out in 1998–2000, which involved 79 Japanese institutions by two-stage cluster sampling of institutions and patients, disclosed that 1124 patients with breast cancer had been subjected to radiotherapy between 1995 and 1997. Breast-conserving therapy had been provided for 866 patients, and mastectomy followed by radiotherapy had been provided for 258 patients. This study deals with the latter patients. The eligibility criteria for this survey included: (i) absence of distant metastases, (ii) ipsilateral lesion, (iii) absence of prior or concurrent malignancies, (iv) absence of prior history of radiotherapy for breast cancer and (v) absence of collagen vascular disease.
The patient’s clinical records were retrospectively surveyed for work-up and treatment. As for their past history, eight items were evaluated: menopausal state, gravidity, parity, age at first delivery, use of oral contraception, use of estrogen replacement therapy, family history of breast cancer and family history of ovarian cancer. Physical examination included 11 items; affected site, location of primary lesion, clinical size of the primary lesion (longest and shortest diameters), clinical T stage, clinical N stage, distance from the nipple, height, weight, bust and bra size. The use of mammography was also investigated. Surgical management was evaluated: surgical type, level of axillary dissection, number of axillary node specimens and final surgical margin. Pathological examination was evaluated: pathological T stage, tumor size, pathological N stage, number of positive axillary nodes, pathological subtype and hormonal responsiveness. The technique of radiotherapy was evaluated: treatment volume, radiation dose, cast for immobilization, radiation field set-up and quality of radiotherapy. Adjuvant therapy was evaluated: type of chemotherapy and hormonal therapy.
The patient’s clinical records were also reviewed to determine the clinical and pathological stage of the tumors according to the International Union Against Cancer (UICC) (7). University hospitals or cancer centers were defined as Institutes Type A, and other hospitals were defined as Institutes Type B. Differences in proportion were tested by chi-squared test.
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RESULTS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONSACKNOWLEDGMENTSREFERENCES |
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Patient Characteristics
Institutes Type A included 115 patients, and Institutes Type B included 143 patients. The median age of the 258 patients was 53 years (25–83 years). Forty percent of the patients treated in Institutes Type A and 50% of those treated in Institutes Type B were in the postmenopausal state (P = 0.143). There was no big difference in patient characteristics between Institutes Type A and Institutes Type B (Table 1).
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Pretreatment Evaluation Based on History, Physical Examination and Radiological Studies
In general, the compliance rates of pre-treatment evaluation based on history taking, physical examination and radiological study were not very high. The compliance rates were relatively high (70–81%) for evaluation of menopausal status and family history of breast cancer and ovarian cancer, but those of evaluation of gravidity and age at the time of the first delivery were low (24–40%). The compliance rates in Institutes Type B were higher than those in Institutes Type A. Mammography was carried out in only half of the patients.
Evaluation and Management of the Primary Tumor and Regional Lymph Nodes
There were no big differences in tumor characteristics between Institutes Type A and Institutes Type B (Table 1). An invasive ductal cancer was shown in >90% of patients, and pathological T3–4 was shown in 25–35% of patients.
Twenty-two percent of patients were subjected to classical radical (Halsted) mastectomy that included resection of the major and minor pectoral muscles, and 6% of the patients were subjected to simple mastectomy (Fig. 1). Sixty-eight percent of patients were subjected to modified radical mastectomy, and there was no significant difference in the surgical approach between Institutes Type A (69%) and Institutes Type B (67%). The final surgical margin was found to be insufficient in only 4% of patients, and there was no difference in the frequency of a positive margin between Institutes Type A and Institutes Type B. The pathological primary stage could not be determined in 10% of patients.
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, simple mastectomy.As shown in Figure 2, an adequate axillary node dissection, which was defined as the resection of six axillary nodes or more, was performed in >70% of patients. The pathological node stage could be determined in 84% of patients. Half of the patients had more than four positive axillary nodes. There was no big difference in surgical management including surgical type, surgical margin, level of axillary dissection and number of nodes in axillary specimens between Institutes Type A and Institutes Type B (Table 2).
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Radiotherapy
The chest wall was irradiated in only 19% of patients, and radiotherapy was provided more frequently at Institutes Type A than Institutes Type B (26 versus 14%, P = 0.015) (Fig. 3). The median total dose of chest wall irradiation was 50 Gy. Supraclavicular nodes irradiation and/or internal mammary nodes irradiation was carried out in 70–86% of patients.
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Cast or shell for immobilization was used in only 9–20% of patients. Simulation using computed tomography (CT) was carried out in only 29% of patients (Institutes Type A, 39% versus Institutes Type B, 17%; P < 0.001) (Table 3). Dose distribution using CT image or breast contour was obtained in only 32–37% of patients. At Institutes Type B a high-energy beam (>6 MV photon) was applied more frequently than at Institutes Type A (16 versus 2%, P = 0.022).
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Adjuvant Systemic Therapy
Chemotherapy was carried out in 67% of patients, not performed in 20% of patients and no information was available for 13% of patients. Concurrent chemotherapy with radiotherapy was performed in 50–53% of patients (Table 4). Seventy-six percent of the patients who were younger than 50 years of age received chemotherapy, while 59% of the patients who were 50 years of age or older received chemotherapy. Among the 171 patients who received chemotherapy, 55% were treated with non-intensive chemotherapy, which was defined as a regimen that did not include anthracyclines or taxol (Institutes Type A, 32%; Institutes Type B, 22%; P = 0.001), while 45% received intensive chemotherapy that included anthracyclines or taxol.
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Hormonal therapy was carried out in 66% of patients, was not provided for 16% of patients and there was no data in 18% of patients. There was insufficient information regarding estrogen receptors (ER) and/or progesterone receptors (PgR) in 54% of patients. Among 71 patients with ER(+) and/or PgR(+), 73% received hormonal therapy. Incidentally, 56% of patients who showed no endocrine response received hormonal therapy. There was no significant difference regarding the administration of hormonal therapy between Institutes Type A and Institutes Type B.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONSACKNOWLEDGMENTSREFERENCES |
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Chest wall recurrence after mastectomy is a significant problem associated with treatment of locally advanced breast cancer in Western countries (3,8–10). The reported rates of loco-regional failure in patients with positive axillary nodes who were subjected to mastectomy alone and/or were administered chemotherapy ranged from 11 to 44% (11–18). Two prospective studies reported in 1997 demonstrated that postoperative radiotherapy after mastectomy was not only associated with a higher loco-regional control rate but also with a higher overall survival rate (19,20). In contrast, chest wall recurrence after mastectomy is not as common in Japan. There is a report that chest wall recurrence was only 10% in a series of 105 Japanese patients with locally advanced breast cancer (TanyN1bii–3 or T3–4Nany) who did not receive chest wall irradiation (21). Chest wall irradiation has been seldom used after mastectomy, and Japanese radiation oncologists tend to have resorted to postoperative radiotherapy, using the so-called hockey-stick field including ipsilateral internal mammary nodes, supraclavicular nodes and infraclavicular nodes for high risk patients who had multiple positive axillary nodes or an advanced primary tumor (22). In order to resolve this difference we should consider the differences between treatment aspects in Western countries and those in Japan. The discrepancy of the loco-regional recurrence in Japan and in Western countries is a mystery, for which there seems to be no evidence that could readily account for the difference. One of the causes may be the frequency of insufficient surgical margin after mastectomy, as suggested by our report on the difference of surgical management between Japan and United States (23).
This study shows that rates of compliance with the pretreatment evaluation based on history taking and physical examination are not very high. Mammography before surgery was carried out in only half of the patients. The American College of Radiology (ACR) has emphasized the importance of breast cancer-specific history taking, including family history, history of prior therapeutic irradiation, presence of breast implants, date of last menstrual period and symptoms suggestive of metastases (24). It has also recommended physical examination, including tumor size and location, fixation to skin, ratio of breast size to tumor size, evidence of multiple primary tumors, axillary node status, supraclavicular nodes and evidence of locally advanced cancer for the pretreatment work-up. In Japan we should establish a work-up system that includes important elements for patients with breast cancer, and improve the rates of compliance of evaluation.
The technical aspects of the delivery of radiation differed from the guidelines established by the American Society of Clinical Oncology (ASCO) (5). In general, postoperative radiotherapy after mastectomy has been indicated for patients with locally advanced cancers (TanyN1bii–3 or T3–4Nany) (3,19,20). The irradiated area in patients subjected to postoperative radiotherapy after mastectomy included the chest wall and supraclavicular nodes and/or internal mammary nodes. The present data showed that chest wall irradiation was carried out in only 19% of patients. At present it seems that regional irradiation alone has limited value, and that the number of patients undergoing this treatment may decrease in the future (22). In addition, we also found that the radiation technique was inadequate from the present data: use of a high-energy beam (>6 MV) and clinical set-up. Simulation using CT was applied in only one-quarter of the patients. There are only a few radiation oncologists, medical physicists and dosimetrists in Japan, and therefore radiation technologists and radiation oncologists have to calculate the dose distribution. A key point which would improve the quality of radiotherapy is to increase the number of staff in the departments of radiation oncology. Moreover, Institutes Type B may have only one treatment machine, thus the radiation oncologist is unable to select an adequate energy dosage. In the future the import of machines provided with a dual-energy beam may solve this problem. A significant difference was found between the two types of institutions with regard to techniques employed to provide radiotherapy, and this difference should disappear in the future.
The overall survival after modified radical mastectomy was equal to that of classical radical mastectomy (3,13). The Japan Breast Cancer Society surveyed the patients treated in 1997 and showed that classical radical mastectomy was carried out in only 3% of patients, modified radical mastectomy in 60%, and breast-conserving therapy in 30% (24). In the present survey we found that 22% of the patients had been subjected to classical radical mastectomy. This study included many patients who were subjected to aggressive surgery compared with the national average, because we surveyed only the patients with locally advanced breast cancer, who were treated with mastectomy and postoperative radiotherapy. The present data showed that the pathological stage of the primary lesion could be determined in >90% of patients, and most patients were subjected to an axillary dissection that included six or more nodal specimens. There was no significant difference between Institutes Type A and Institutes Type B with regard to surgical management and staging of the primary tumor and regional nodes. In Japan, surgical management for locally advanced breast cancers seems to be relatively mature.
The consensus meeting held in St Gallen in 1998 recommended that adjuvant therapy should be provided according to risk factors, including menopausal state, tumor bulk, axillary node status and endocrine responsiveness (4). The present study showed that there was insufficient information on ER in half of the patients, and that half of the patients without endocrine response were subjected to inadequate hormonal therapy. We also found some problems in adjuvant systemic chemotherapy. The administration of adjuvant chemotherapy for premenopausal patients with positive nodes had been the established standard practice since the 1980s (26). On average, anthracycline-containing therapies were superior to average CMF (cyclophosphamide, methotrexate, fluorouracil) and to other non-intensive chemotherapy (6). The present data showed that half of the patients were treated with non-intensive chemotherapy. As there are few medical oncologists in Japan, surgical oncologists have to provide adjuvant chemotherapy and hormonal therapy for patients with breast cancer. Non-intensive chemotherapy, such as 5-FU (5-fluorouracil) or CMF, is considered convenient for surgical oncologists. A key point to improve the quality of adjuvant therapy for patients with locally advanced breast cancer is to increase the number of medical oncologists. But since there are few medical oncologists in Japan at present, surgical oncologists should perform adjuvant systemic therapy according to the consensus meeting of St Gallen (4).
In this study, we examined the problem of therapeutic process including work-up, surgery, radiotherapy and systemic therapy for patients subjected to mastectomy and postoperative radiotherapy in Japan. We have now conducted further studies to identify problems associated with the process of care for patients undergoing postmastectomy radiotherapy in Japan compared with those in the United States (23).
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CONCLUSIONS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONSACKNOWLEDGMENTSREFERENCES |
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The compliance rates of pretreatment work-up for patients treated with mastectomy and postoperative radiotherapy in Japan were not very high. Surgical management of the primary tumor and regional nodes seemed to be relatively mature, and there was little difference regarding surgical management between Institutes Type A and Institutes Type B. There is room for improvement regarding radiotherapy and adjuvant systemic therapies. In the field of radiotherapy, a significant difference was found between treatment techniques employed at Institutes Type A and Institutes Type B.
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONSACKNOWLEDGMENTSREFERENCES |
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This study was supported by Grant-in-Aid for Cancer Research (10-17, 14-6) from the Ministry of Health, Labor and Welfare of Japan and a Grant from the Japan Society for the Promotion of Science. We thank all radiation oncologists who participated in this study. Their efforts in providing information to us makes these surveys possible. Presented at the First Japan/United States PCS Workshop, San Francisco, CA, November 2001.
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FOOTNOTES |
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+ For reprints and all correspondence: Naoto Shikama, Department of Radiology, Shinshu University, School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan. E-mail: shikama{at}hsp.md.shinshu-u.ac.jp
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Received March 14, 2003; accepted August 3, 2003
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