Japanese Journal of Clinical Oncology Advance Access originally published online on April 12, 2006
Japanese Journal of Clinical Oncology 2006 36(4):193-196; doi:10.1093/jjco/hyl007
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© 2006 Foundation for Promotion of Cancer Research
The Use of Recursive Partitioning Analysis Grouping in Patients with Brain Metastases from Non-Small-Cell Lung Cancer
ükrü Erkal
Department of Radiation Oncology, 
nönü University Faculty of Medicine, Malatya, Turkey
For reprints and all correspondence: Haldun ükrü Erkal, MD, Department of Radiation Oncology, nönü University Faculty of Medicine, Malatya, TR-44280, Turkey. E-mail: hserkal{at}inonu.edu.tr
Received December 5, 2005; accepted January 30, 2006
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Abstract |
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 TOP Abstract INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONSReferences |
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Background: This study evaluates the use of recursive partitioning analysis (RPA) grouping in an attempt to predict the survival probabilities in patients with brain metastases from non-small-cell lung cancer (NSCLC).
Methods: Seventy-two patients with brain metastases from NSCLC treated with radiation therapy were included in the study. Sixty-three patients were male and nine patients were female. Their median age was 57 years and their median Karnofsky performance status was 70. At the time of brain metastases, there was no evidence of the intrathoracic disease in 27 patients and the extrathoracic disease was limited to the intracranial disease in 42 patients. In accordance with RPA grouping, 12 patients were in Group 1, 24 patients were in Group 2, and 36 patients were in Group 3. Radiation therapy was delivered to the whole brain at a dose of 30 Gy in 10 fractions in most of the patients.
Results: The median survival time was 7 months for Group 1, 5 months for Group 2 and 3 months for Group 3. The survival probability at 1 year was 50% for Group 1, 26% for Group 2 and 14% for Group 3.
Conclusions: This study presents evidence supporting the use of RPA grouping in an attempt to predict the survival probabilities in patients with brain metastases from NSCLC.
Key Words: non-small-cell lung cancer • brain metastases • radiation therapy • recursive partitioning analysis
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INTRODUCTION |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONSReferences |
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For patients with brain metastases, radiation therapy to the whole brain might be questionable for those having shorter life expectancy (1), whereas the addition of surgical resection (2) or stereotactic radiation therapy (3) might be justified for those having longer life expectancy. Therefore, the ability to foresee the survival probabilities in patients with brain metastases attains tremendous importance with regard to the allocation of these patients to conservative as opposed to aggressive treatment strategies. The use of recursive partitioning analysis (RPA) grouping, as described by the Radiation Therapy Oncology Group (RTOG), has been proposed as a tool for the stratification of patients with brain metastases with such intent (4). For a better understanding of the robustness of this proposal, it will be necessary to evaluate RPA grouping in distinct, yet homogeneous, groups of patients with brain metastases (5). This study evaluates the use of RPA grouping in an attempt to predict the survival probabilities in patients with brain metastases from non-small-cell lung cancer (NSCLC).
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PATIENTS AND METHODS |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONSReferences |
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Seventy-two consecutive patients with brain metastases from NSCLC, treated with radiation therapy with palliative intent from October 2002 through June 2005 in the Department of Radiation Oncology at
nönü University Faculty of Medicine, were included in the study. Clinical, pathological and radiological data for these patients were reviewed and retrospectively classified (Table 1). Sixty-three patients (87%) were male and nine patients (13%) were female. Their ages ranged from 34 years to 79 years (median, 57 years), and their Karnofsky performance status (KPS) ranged from 30 to 90 (median, 70).
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The diagnosis of NSCLC was based on histopathological evaluation in all of the patients. Computed tomography of the thorax was available in all patients to evaluate the extent of the intrathoracic disease. At the time of brain metastases, there was no evidence of the intrathoracic disease in 27 patients (38%). Computed tomography of the abdomen and bone scintigraphy were available in most of the patients to evaluate the extent of the extrathoracic disease. At the time of brain metastases, the extrathoracic disease was limited to intracranial disease in 42 patients (58%).
For 23 patients (32%), the diagnosis of NSCLC coincided with the diagnosis of brain metastases. At the time of brain metastases, two patients (9%) did not experience any symptoms, 11 patients (48%) experienced headache, six patients (26%) experienced neurological dysfunction and four patients (17%) experienced both headache and neurological dysfunction. Regarding neurological dysfunction, five patients experienced focal weakness, two patients experienced seizures, one patient experienced impairment of gait, one patient experienced impairment of speech and one patient experienced impairment of cognition. For the remaining 49 patients (68%), the time from the diagnosis of NSCLC to the diagnosis of the brain metastases ranged from 1 to 23 months (median, 6 months). At the time of brain metastases, one patient (2%) did not experience any symptoms, 24 patients (49%) experienced headache, 10 patients (20%) experienced neurological dysfunction and 14 patients (29%) experienced both headache and neurological dysfunction. Regarding neurological dysfunction, nine patients experienced focal weakness, six patient experienced impairment of gait, four patients experienced impairment of cognition, three patients experienced seizures and two patients experienced impairment of vision.
The diagnosis of brain metastases was based on computed tomography of the brain in all of the patients. Magnetic resonance imaging of the brain was available in most of the patients to evaluate the extent of the intracranial disease. The number of brain metastases was 1 in 19 patients (26%) and more than one in 53 patients (74%). In accordance with RPA grouping as adopted for patients with brain metastases from NSCLC (Table 2), 12 patients (17%) were in Group 1, 24 patients (33%) were in Group 2 and 36 patients (50%) were in Group 3. Surgical resection of the intracranial disease was not attempted in any of the patients. Radiation therapy was delivered to the whole brain at a dose of 30 Gy in 10 fractions of 3 Gy in most of the patients.
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The survival time was defined as the time from the diagnosis of the brain metastases to death. Patients who were alive were classified as censored observations at the time of the last follow-up. The survival probabilities were estimated using the method of Kaplan and Meier. Statistical analysis was performed using the ‘10.0’ version of the ‘SPSS for Windows’ software package.
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RESULTS |
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The median follow-up was 4 months for all of the patients. The median follow-up was 9 months for patients in Group 1, 5 months for patients in Group 2 and 3 months for patients in Group 3. The median survival time was 4 months for all of the patients. The median survival time was 7 months for patients in Group 1, 5 months for patients in Group 2 and 3 months for patients in Group 3.
The survival probability at one year was 26% (95% confidence interval = 10% through 53%, number of censored observations = 9) for all of the patients. The survival probability at 1 year was 50% (95 % confidence interval = 19% through 81%, number of censored observations = 4) for the patients in Group 1, 26% (95% confidence interval = 5% through 70%, number of censored observations = 3) for patients in Group 2 and 14% (95% confidence interval = 1%through 67%, number of censored observations = 2) for patients in Group 3 (Fig. 1).
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DISCUSSION |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONSReferences |
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For patients with brain metastases, the treatment strategy relies on radiation therapy to the whole brain in an attempt to delay the progression of the intracranial disease for those having shorter life expectancy, whereas the addition of surgical resection or stereotactic radiation therapy in an attempt to eradicate the intracranial disease constitutes the treatment strategy for those having longer life expectancy (6). Hence, the ability to foresee the survival probabilities in patients with brain metastases might enable the allocation of these patients to conservative as opposed to aggressive treatment strategies. RPA grouping has been described by the RTOG in order to provide a stratification tool for patients with brain metastases with regard to their allocation to distinct treatment strategies (4). Through the use of RPA grouping, novel treatment strategies might be investigated in relatively homogeneous groups of patients with brain metastases, thus eliminating the selection bias in clinical trials (7). However, RPA grouping has not been unanimously adopted, in particular for those not participating in clinical trials (8). Besides, patients participating in clinical trials might display relatively favourable disease characteristics (9). Therefore, modifications (10), as well as further stratifications (11), of the established RPA groups have been proposed for patients not participating in clinical trials as well.
RPA grouping as adopted for patients with brain metastases from NSCLC underscores two patient characteristics, namely the age and the KPS, in addition to two disease characteristics, namely the evidence of the intrathoracic disease and the evidence of the extrathoracic disease other than the intracranial disease. The age and the KPS might be regarded as accurately assigned characteristics. On the other hand, once the diagnosis of the brain metastases is established, the evaluation of the extent of the intrathoracic disease is somewhat arbitrary and the effort to evaluate the extent of the extrathoracic disease is typically modest, particularly for patients not participating in clinical trials. In the present study, computed tomography of the thorax was available in all of the patients to evaluate the extent of the intrathoracic disease, and computed tomography of the abdomen and bone scintigraphy were available in most of the patients to evaluate the extent of the extrathoracic disease. Therefore, the patient characteristics as well as the disease characteristics were accurately assigned, resulting in improved reliability in terms of both grouping and evaluation.
Kepka et al. (8) reported a median survival time of 4 months for 190 patients with brain metastases from NSCLC. In that study, the median survival time was reported as 6 months for patients in Group 1, 3.5 months for patients in Group 2 and 3 months for patients in Group 3. Likewise, Rodrigus et al. (12) reported the median survival time as 3.1 months for 250 patients with brain metastases from NSCLC. In that study, the median survival time was 4.8 months for patients in Group 1, 2.8 months for patients in Group 2 and 2 months for patients in Group 3. The present study is in sound agreement with the retrospectively classified studies reporting institutional experiences on patients with brain metastases from NSCLC (8,12), with a median survival time of 4 months for all of the patients and a median survival time of 7 months, 5 months and 3 months, respectively, for patients in Group 1, Group 2 and Group 3. There exists no consensus on the optimal treatment strategies for patients with brain metastases from NSCLC (13). The median survival time of 3 months for patients in Group 3 in the present study argues in favour of the use of abbreviated, rather than protracted, radiation therapy strategies for these patients. Moreover, the median survival time of 7 months for patients in Group 1 in the present study, despite the fact that surgical resection of the intracranial disease was not attempted in any of these patients, suggests that the use of aggressive treatment strategies are warranted for these patients.
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CONCLUSIONS |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONSReferences |
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This study presents evidence supporting the use of RPA grouping in an attempt to predict the survival probabilities in patients with brain metastases from NSCLC.
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References |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONSReferences |
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