Japanese Journal of Clinical Oncology Advance Access originally published online on November 12, 2008
Japanese Journal of Clinical Oncology 2009 39(1):22-26; doi:10.1093/jjco/hyn124
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© The Author (2008). Published by Oxford University Press. All rights reserved
Questionnaire Survey of Treatment Choice for Breast Cancer Patients with Brain Metastasis in Japan: Results of a Nationwide Survey by the Task Force of the Japanese Breast Cancer Society
1 Hyogo Cancer Center, Division of Medical Oncology, Hyogo
2 National Cancer Center Hospital, Division of Medical Oncology, Tokyo
3 Kyoto University, Department of Therapeutic Radiology and Oncology, Kyoto
4 Kansai Rousai Hospital, Division of Surgery, Hyogo
5 Shikoku Cancer Center Hospital, Division of Therapeutic Radiology, Ehime
6 Yokohama Rousai Hospital, Division of Neurosurgery, Kanagawa
7 Juntendo University, Department of Radiation Oncology, Tokyo
8 Satiama Cancer Center, Division of Pathology, Saitama
9 Hiei Hospital, Division of Surgery, Kyoto, Japan
For reprints and all correspondence: Koji Matsumoto, Hyogo Cancer Center, Division of Medical Oncology, 13-70 Kitaoji-cho, Akashi, Hyogo 673-8558, Japan. E-mail: kojmatsu{at}hp.pref.hyogo.jp
Received May 2, 2008; accepted October 5, 2008
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Abstract |
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 TOP Abstract INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONFundingReferences |
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Objective: A nationwide survey was performed to investigate the current patterns of care for brain metastasis (BM) from breast cancer in Japan.
Method: A total of 351 survey questionnaires were sent to community or academic breast oncologists who were members of the Japanese Breast Cancer Society as of December 2005. The questionnaire consists of 40 multiple choice questions in eight categories.
Results: Of 240 institutions sent survey questionnaires, 161 (67.1%) answered; 60% of institutions answered with ‘<5’ patients with BM every year; almost half (83 of 161) screened for BM in asymptomatic patients; surgical resection was rarely performed, as ~75% of institutions (118 of 160 institutions) answered ‘none or one case of surgery per year’; 27% (41 of 154) preferred stereotactic radiosurgery (SRS) over whole-brain radiotherapy (WBRT) as the initial treatment in all cases, although ~70% (100 of 154) of them answered ‘depend on cases’. The preference for SRS over WBRT mainly depends on the impressions of breast oncologists about both safety (late normal tissue damage and dementia in WBRT) and efficacy (better local control by SRS). Eighty-one percent (117 of 144) of institutions did not limit the number of SRS sessions as far as technically applicable.
Conclusion: SRS is widely used as the first choice for BM from breast cancer in Japan. Considerable numbers of Japanese breast oncologists prefer SRS over WBRT as the initial treatment for BM. A randomized trial comparing SRS and WBRT is warranted.
Key Words: breast cancer • brain metastasis • stereotactic radiosurgery • whole-brain radiotherapy
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INTRODUCTION |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONFundingReferences |
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Brain metastasis (BM) is one of the most devastating complications of cancer and is usually associated with poor prognosis. The incidence of BM is high among patients with breast cancer, 10–20% in general (1). The incidence of BM in patients with HER2/neu over-expression is considered to be especially high, around 25–40% (2–5).
Whole-brain radiotherapy (WBRT) is the standard treatment for most patients with BM. For patients with a single BM, surgery followed by WBRT is superior to WBRT alone (6,7), although some studies does not support this (8). For patients with limited number (usually one to three) of BM, there is a controversy as discussed later (9). For patients with multiple (usually four or more) BM, WBRT is standard treatment.
Stereotactic radiosurgery (SRS) was developed in 1950s (10) and is now widely used as an alternative to surgery, WBRT and sometimes both. WBRT followed by SRS boost has also been studied (11,12) and is considered a standard treatment for patients with a single metastasis. Radiation-induced necrosis, especially after WBRT, is a rare but irreversible complication (13), which leads to the frequent use of SRS for the treatment of BM.
Withholding WBRT, SRS alone as upfront therapy is thought to be an alternative to BM (14–17). One prospective study compared SRS alone with SRS plus WBRT (18), which did not show a statistically significant difference in terms of overall survival. A relatively small sample size, decreased local control rate and lack of difference in neurological adverse events made it difficult to conclude that SRS alone was not inferior to SRS plus WBRT (19). Although this evidence confirms WBRT as standard treatment, SRS alone is widely used in daily practice.
BM in breast cancer is unique, compared with BM in other primaries, for certain reasons. The first is the high incidence of BM in breast cancer, especially in patients with the Her2/neu subtype, which has already been mentioned. The second is, BM in breast cancer is more radiosensitive than that in other primary such as non-small cell lung cancer or renal cell carcinoma. This may lead to better local control of BM by WBRT only. The third is the better prognosis after diagnosis of BM, especially in patients with Her2/neu positive subtype (20). This may lead to increased concern about radiation necrosis and failure of local control. For these reasons, BM in breast cancer is unique in terms of risk-benefit balance. A prospective trial, ideally exclusive to breast cancer, is needed for optimal usage of SRS.
As preparation for a future prospective trial, the task force of the Japanese Breast Cancer Society made a questionnaire survey of treatment choices for breast cancer patients with BM.
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PATIENTS AND METHODS |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONFundingReferences |
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A total of 351 survey questionnaires were sent to community or academic breast oncologists who were board members of the Japanese Breast Cancer Society, in December 2005. For most institutions, one breast oncologist was selected from each institution. For some large institutions, two or more oncologists were selected, because they have multiple hospitals or divisions that may have different treatment strategies. To avoid duplicated answers from the same treatment team, we attached the statement asking to unite one answer from one hospital or divisions. The questionnaire consists of 40 multiple choice questions in about eight categories, such as characteristics of hospitals, screening for BM, operation, radiation, re-irradiation, chemotherapy, SRS and cost.
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RESULTS |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONFundingReferences |
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Of 240 institutions to which we sent survey questionnaires, 161 (67.1%) answered. More than 90% of answers were obtained from surgical oncologists; the remainders were radiation and medical oncologists, reflecting the current situation that most patients with breast cancer are treated by surgeons in Japan. The background characteristics of each institution are summarized in Table 1. Both small and large institutions were included in this survey. In many institutions, BM was a rare complication (60% of institutions answered ‘<5’ patients with BM every year), but some institutions treat many BM patients (>20 patients per year). In 75% (125 of 155) of institutions, the treatment decision is made by a neurosurgeon and/or radiation oncologist.
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More than half the institutions (83 of 161) screened for BM, although no evidence exists to support a screening strategy (Table 2). Timing of screening for BM differed, although more than half of the institutions with a screening strategy screen at disease progression. Some institutions screened before starting trastuzumab.
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Surgical resection was less frequently used as local therapy for BM because
75% of the institutions (118 of 160) answered ‘none or one case who received surgical resection per year’ (Table 3). The infrequent choice of surgical resection might be a result of the rigid indications for surgery. More than 60% of institutions answered that no evidence of systemic disease except for BM, or controlled systemic disease by systemic therapy was crucial for surgical resection. WBRT, not SRS, was dominantly used for postoperative radiotherapy.
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The indication for WBRT is summarized in Table 4. Different from surgical resection, it was not dependent on prognosis (87% of institutions answered that they considered radiotherapy regardless of the prognosis, for symptom relief). Even in patients with a poor performance status, WBRT can be used. More than 30% of institutions (52 of 161) answered that they would consider WBRT for patients with ECOG PS 4, if clinically needed. Eighty-one percent of institutions (124 of 154 institutions) interrupted chemotherapy during WBRT, although some institutions did not.
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Table 5 summarizes the questions about re-irradiation for patients who had progressed to BM after WBRT. More than 80% of institutions answered that they did not repeat radiotherapy except for SRS. Interval as an indication for re-irradiation is controversial. Sixteen institutions needed an interval before re-irradiation, whereas another 14 institutions did not. Regarding the risk of re-irradiation, most surgeons estimated that the risk was greater than a few percent, but did not present their estimate to patients numerically.
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Table 6 summarizes the questions about SRS and cost. Only 7% (13 of 154) of institutions gave WBRT as their first choice, although
70% (100 of 154) answered ‘depend on cases’. The indication for SRS according to the metastatic site, size and the number of BMs largely influenced the treatment decision. Concerning the indication for SRS, 98% (98 of 100) of institutions limited SRS for only small (<3 cm) lesions. Seventy-one percent (76 of 108) of institutions choose SRS only for patients with a limited number (<5 lesions) of BMs. However, 81% (117 of 144) of institutions did not limit the number of sessions as long as neurosurgeons technically permitted SRS. There was no consensus concerning prognosis and PS as indications for SRS. SRS was preferred to WBRT for both safety (less dementia) and efficacy (better BM control) reasons. The cost of SRS was not precisely estimated by the majority of surgeons.
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DISCUSSION |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONFundingReferences |
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This survey revealed that SRS is widely used as the first choice for BM treatment for patients with breast cancer in Japan. Many Japanese breast oncologists prefer SRS to WBRT as radiation therapy against BM. There are discrepancies between NCCN guideline recommendations and the practice in Japan. For example, for a limited number of BM, 30% of Japanese breast oncologists use SRS as adjuvant treatment although NCCN guidelines recommend WBRT as adjuvant treatment after surgery. For multiple BM, 30% of Japanese breast oncologists use SRS for patients with more than five BM, although NCCN guidelines recommend WBRT. For both a limited number of, and multiple, BM 60% of Japanese breast oncologists use SRS, although NCCN guidelines recommend WBRT for patients with systemic disease refractory to aggressive treatment. What causes these discrepancies, a preference for SRS and reluctance to use WBRT? Our survey revealed that Japanese breast oncologists believe that SRS is a safer and more effective treatment than WBRT, as shown in Table 6. Interestingly, one of the major concerns about WBRT was dementia, although 70% had not actually experienced it. Nonetheless, they did not limit the number of sessions for SRS. It seems that they believe that SRS is much safer than WBRT. Lack of recognition of the precise cost of SRS also enhances this preference for SRS, because the current national insurance system covers 70–90% of the total costs of SRS, which costs 500 000 yen per session.
The present study suggests issues for future trials. First, as shown in Table 1, the treatment decision for BM is shared by neurosurgeons and radiation oncologists, so their collaboration is essential. Another suggestion is the consideration of screening. More than half of the institutions had screened for BM although there is no supporting evidence. This should be taken into account when designing a clinical trial because screening may detect BM earlier in its clinical course, influencing the treatment choice (fewer lesions may lead to more SRS) and the survival of BM patients as a result of lead-time bias. Preference for SRS and its reasons are also important. A future trial on SRS should answer two questions: first, is limitless repetition of SRS safer than WBRT in terms of the long-term adverse effects of radiotherapy? and second, is SRS superior to WBRT in terms of local control? To answer these two questions, we need a prospective trial comparing WBRT with SRS for patients with breast cancer having limited number, and small size, of BM. This kind of randomized study would need too large a sample size to be conducted in Japan only, so international collaboration would be needed.
One limitation of the present study is that a questionnaire from one oncologist at an institution does not demonstrate the pattern of practice at the institution perfectly, because there could be many biases such as recall bias, response bias and so on. Although the background of institutions shown in Table 1 seems to show that this survey describes the current pattern of practice in Japan well, actual data from each institution are more helpful. We have therefore planned a historical cohort study to reduce these biases.
In conclusion, the present study showed that SRS alone is widely used as BM treatment for patients with breast cancer in Japan. To address the issues of both safety and efficacy, a future prospective trial studying the optimal usage of screening, SRS and WBRT is warranted.
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Funding |
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This study is supported by Japanese Breast Cancer Society.
Conflict of interest statement
None declared.
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References |
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