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Keywords:

  • brain metastases;
  • stereotactic radiosurgery;
  • whole-brain radiotherapy;
  • recursive partitioning analysis class

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

BACKGROUND.

The authors investigated whether stereotactic radiosurgery (SRS) alone improved outcomes for patients in recursive partitioning analysis (RPA) Classes 1 and 2 who had 1 to 3 brain metastases compared with whole-brain radiotherapy (WBRT).

METHODS.

Data regarding 186 patients in RPA Classes 1 and 2 who had 1 to 3 brain metastases and who received either 30 to 40 grays (Gy) of WBRT (n = 91 patients) or 18 to 25 Gy SRS (n = 95 patients) were analyzed retrospectively. Eight other potential prognostic factors were evaluated regarding overall survival (OS), entire brain control (BC), local control (LC) of treated metastases, and brain control distant from treated metastases (distant control [DC]): Those 8 factors were age, sex, performance status, tumor type, number of brain metastases, extracranial metastases, RPA class, and interval from tumor diagnosis to radiotherapy.

RESULTS.

On multivariate analysis of OS, age ( risk ratio [RR], 1.51; P = .024), Karnofsky performance status (KPS) (RR, 1.98; P = .002), and extracranial metastases (RR, 2.26; P < .001) were significant, whereas the radiation regimen was not significant (P = .89). On multivariate analysis of BC, only the radiation regimen (RR, 1.33; P = .003) was found to be significant. On multivariate analysis of LC, radiation regimen (RR, 1.63; P < .001) and sex (RR, 1.62; P = .022) were significant. On multivariate analysis of DC, KPS (RR, 1.85; P = .049) and extracranial metastases (RR, 1.69; P = .047) were significant. The radiation regimen was not found to be significant even on univariate analysis (P = .80). In RPA class subgroup analyses, BC and LC were better after SRS than WBRT for patients in RPA Classes 1 and 2, whereas OS and DC did not differ significantly.

CONCLUSIONS.

For patients in RPA Classes 1 and 2 who had 1 to 3 brain metastases, SRS alone was associated with improved BC and LC compared with 30 to 40 Gy WBRT, whereas OS and DC were not significantly different. Similar results were observed in separate subgroup analyses of patients in RPA Class 1 and RPA Class 2. Cancer 2007. © 2007 American Cancer Society.

The survival prognosis for most patients with brain metastases is poor and is measured in months.1, 2 The prognosis for patients who have 1 to 3 brain metastases appears to be better than that for patients who have >3 lesions.3, 4 Therefore, the treatment of 1 to 3 brain metastases differs from that of multiple lesions. Although whole-brain radiotherapy (WBRT) is the most frequently treatment for multiple metastases, surgical resection of metastases and stereotactic radiosurgery (SRS) are important options for a limited number of metastases. However, randomized studies comparing SRS with surgical resection are not available. A small, uncontrolled, retrospective study that compared SRS with surgical resection for solitary brain metastasis of a suitable size (≤4 cm) suggested that SRS provided better local control (LC) but similar survival compared with resection.5 Furthermore, it should be kept in mind that considerable proportions of brain metastases are not accessible for resection, in particular, those in the brainstem and in the deep white and gray matter. These lesions can be treated reasonably only with radiotherapeutic options such as WBRT and SRS.

SRS and brain surgery are sophisticated techniques that are not available in many centers worldwide. Thus, WBRT is often the only available alternative and thus remains an important treatment option both for single or multiple metastases. Most studies that included SRS for the treatment of 1 to 3 lesions compared WBRT alone versus WBRT plus a stereotactic boost.6–9 Those studies suggested that better brain control was achieved with the combined approach than with WBRT alone, although no significant difference was reported in median survival.

Hasegawa et al. suggested that brain metastases are well controlled with SRS alone and that WBRT, in addition to SRS, may be omitted to reduce the risk of radiation-related toxicity.10 Those authors suggested that SRS alone was a reasonable alternative to WBRT plus SRS. Sneed et al. suggested in 2 retrospective studies that the omission of WBRT in the initial management of patients who undergo radiosurgery does not appear to compromise survival.11, 12

However, the studies by Sneed et al. and Hasegawa et al. did not compare SRS alone with WBRT alone. A study by Chougule et al. compared 31 patients who received 10 × 3 grays (Gy) of WBRT alone and 36 patients who underwent with γ-knife radiosurgery alone.8 The 1-year brain LC rates in that study were 62% and 87%, respectively (P value not stated), and the median survival was 9 months and 7 months, respectively. The difference was not significant. However, these data have been published only in abstract form. Thus, there is a distinct lack of data comparing SRS alone with WBRT alone for the treatment of brain metastases. Such a comparison is performed in the current study of 186 patients who had 1 to 3 brain lesions.

The prognosis for patients with brain metastases is associated strongly with their recursive partitioning analysis (RPA) class. Using data from 3 Radiation Therapy Oncology Group (RTOG) brain metastases trials, RPA was performed to define prognostic factors.13 The Karnofsky performance status (KPS), age, primary tumor status (controlled vs uncontrolled), and extracranial metastases were the most relevant prognostic factors. On the basis of these factors, 3 prognostic classes were defined: RPA Class 1 (KPS ≥70%; age <65 years; controlled primary tumor; and no extracranial metastases), RPA Class 1 (KPS ≥70%; age ≥65 years, and/or uncontrolled primary tumor, and/or extracranial metastases), and RPA Class 3 (all patients with KPS <70%). The median survivals for patients in RPA Classes 1, 2, and 3 were 7.1 months, 4.2 months, and 2.3 months, respectively.13 The appropriate treatment may vary with RPA class. Therefore, in the current study, we compared the outcome of the radiation regimens for the entire cohort and for RPA Classes 1 and 2.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

The data regarding 186 patients who were treated for 1 to 3 brain metastases between 1993 and 2005 with either WBRT (n = 91 patients; Group A; treated between 1999 and 2005) or SRS (n = 95 patients; Group B; treated between 1993 and 2005) were analyzed retrospectively. Only patients in RPA Classes 1 and 2 were included in the current study, because patients with a poor performance status (patients in RPA Class 3) usually are not selected for SRS. Group A patients received 10 × 3 Gy or 20 × 2 Gy of WBRT. Group B patients received from 18 to 25 Gy of SRS (median dose, 23.5 Gy) either as linear accelerator-based SRS (n = 66 patients) or as γ-knife SRS (n = 29 patients). Further criteria for inclusion were as follows: no prior radiotherapy (RT) to the brain, confirmation of metastases by computed tomography scanning or magnetic resonance imaging, size of the metastases ≤4 cm, and administration of dexamethasone (12–32 mg/day) during RT. The selection of the treatment regimen was influenced by the year of treatment (SRS has been available in our institutions only since 1999), by the length of the waiting list of patients (limited capacities of SRS), and by the patient's decision (some patients refused to undergo SRS). WBRT was performed with a linear accelerator and a 6- to 10-megavolt photon beam; SRS was performed either as linear accelerator-based SRS or as γ-knife SRS. The total dose of SRS mentioned above represents the dose at the tumor-surrounding isodose. The data for this analysis were obtained from the patients, their general practitioners, treating oncologists, and patient files. The patient characteristics are summarized in Table 1.

Table 1. Patient Characteristics of the 2 Treatment Groups
CharacteristicNo. of patients (%)P
Entire series (n = 186)WBRT (n = 91)SRS (n = 95)
  1. WBRT indicates whole-brain radiotherapy; SRS, stereotactic radiosurgery; KPS, Karnofsky performance status; RPA, recursive partitioning analysis; RT, radiotherapy.

Age, y  
 ≤6090 (48)46 (51)44 (46) 
 >6096 (52)45 (49)51 (54).75
Sex  
 Women95 (51)44 (48)51 (54) 
 Men91 (49)47 (52)44 (46).68
KPS  
 70-80144 (77)71 (78)73 (77) 
 90-10042 (23)20 (822)22 (23).96
Primary tumor  
 Breast cancer31 (17)16 (18)15 (16) 
 Lung cancer69 (37)36 (40)33 (35) 
 Other tumors86 (46)39 (43)47 (49).83
No. of brain metastases
 198 (53)45 (49)53 (56) 
 2–388 (47)46 (51)42 (44).63
Extracranial metastases  
 No97 (52)47 (52)50 (53) 
 Yes89 (48)44 (48)45 (47).95
RPA class  
 Class 166 (35)31 (34)35 (37) 
 Class 2120 (65)60 (66)60 (63).89
Interval from tumor diagnosis to RT, mo
 ≤1591 (49)47 (52)44 (46) 
 >1595 (51)44 (48)51 (54).68

In addition to the treatment regimen, 8 other potential prognostic factors were evaluated regarding the endpoints survival (OS), entire brain control (BC) (ie, freedom from recurrent metastases in the entire brain), LC of the treated metastases, and brain control distant from the treated metastases (DC). The 8 potential prognostic factors included age (≤60 years vs >60 years; median age, 60 years), sex, KPS (70–80 vs KPS 90–100), primary tumor type (breast cancer vs lung cancer vs other tumors), number of brain metastases (1 vs 2–3), presence of extracranial metastases at the time of RT, RPA class (Class 1 vs Class 2), and the interval between tumor diagnosis and RT (≤15 months vs >15 months; median interval, 15 months). Subgroup analyses were performed for the 2 RPA classes to evaluate whether patients in either RPA class benefit from one of the compared therapies.

The patients were followed until death or for 6 to 49 months (median follow-up, 13 months) after RT. Entire BC was defined as the absence of new or recurrent brain metastases (BC = LC + DC). LC was defined as the absence of recurrence of the treated brain metastases. DC was defined as the absence of recurrence of brain metastases other than the treated brain metastases. Local or distant brain failure was confirmed by computed tomography scanning or magnetic resonance imaging. The time to any endpoint was measured from the completion of RT. Patient characteristics were compared with the chi-square test. Survival, BC, and LC rates were calculated by using the Kaplan-Meier method.14 The differences between the Kaplan-Meier curves were determined with the log-rank test (univariate analysis). The prognostic factors that were identified as significant (P < .05) were included in a multivariate analysis, which was performed with the Cox proportional hazards model. The acute toxicity rates were assessed according to version 2.0 of the Common Toxicity Criteria, and the late toxicity rates were assessed according to RTOG criteria.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

The median survival after RT was 9 months for the entire cohort, 7 months for Group A patients, and 13 months for Group B patients. Both treatment groups were balanced for the other potential prognostic factors that were investigated (Table 1). Table 2 summarizes the impact of the potential prognostic factors on OS (univariate analysis). On univariate analysis, improved OS was associated with SRS (vs WBRT), age ≤60 years (vs age >60 years), KPS 90–100 (vs KPS 70–80), lack of extracranial metastases, and RPA Class 1 (vs RPA Class 2). The RPA class was not included in the multivariate analysis, because it takes into account age, KPS, and extracranial metastases. On multivariate analysis, age (relative risk [RR], 1.51; 95% confidence interval [95% CI], 1.06–2.17 [P = .024]), KPS (RR, 1.98; 95% CI, 1.28–3.17 [P = .002]), and extracranial metastases (RR, 2.26; 95% CI, 1.43–3.64 [P < .001]) maintained significance, whereas the radiation regimen lost significance (RR, 1.04; 95% CI, 0.54–1.87 [P = .89]).

Table 2. Results of the Univariate Analysis of Survival
CharacteristicAt 6 mo, %At 12 mo, %At 24 mo, %P
  1. WBRT indicates whole-brain radiotherapy; SRS, stereotactic radiosurgery; KPS, Karnofsky performance status; RPA, recursive partitioning analysis; RT, radiotherapy.

Radiation regimen    
 WBRT (n = 91)593313 
 SRS (n = 95)685219.045
Age, y    
 ≤60 (n = 90)725318 
 >60 (n = 96)563316.021
Sex    
 Women (n = 95)665020 
 Men (n = 91)623614.16
KPS    
 70–80 (n = 144)583610 
 90–100 (n = 42)856436<.001
Primary tumor    
 Breast cancer (n = 31)776622 
 Lung cancer (n = 69)674117 
 Other tumors (n = 86)563615.34
No. of brain metastases    
 1 (n = 98)654518 
 2–3 (n = 88)623915.73
Extracranial metastases    
 No (n = 97)805428 
 Yes (n = 89)46304<.001
RPA class    
 Class 1 (n = 66)835824 
 Class 2 (n = 120)533412.002
Interval from tumor diagnosis to RT, mo
 ≤15 (n = 91)603519 
 >15 (n = 95)674916.13
All patients (n = 186)644317 

A recurrence anywhere in the brain occurred in 110 patients (59%) after a median interval of 5.5 months (range, 0–27 months). Forty-seven patients had a recurrence of the treated metastases, 20 patients had a recurrence distant from the treated metastases, and 41 patients had both. The potential prognostic factors in relation BC are summarized in Table 3 (univariate analysis). On univariate analysis, improved BC was associated significantly with SRS (vs WBRT), being a woman (vs being a man), KPS 90-100 (vs KPS 70–80), and breast cancer (vs lung cancer and other tumors). On multivariate analysis, only the radiation regimen remained significant (RR, 1.33; 95% CI, 1.10–1.61 [P = .003]). A trend toward significance was observed for KPS (RR, 1.47; 95%CI, 0.93–2.38 [P = .09]) and for tumor type (RR, 1.29; 95% CI, 0.96–1.75 [P = .09]). Sex lost significance (RR, 1.39; 95% CI, 0.93–2.11 [P = .11]).

Table 3. Results of the Univariate Analysis of Overall Brain Control
CharacteristicAt 6 mo, %At 12 mo, %At 24 mo, %P
  1. WBRT indicates whole-brain radiotherapy; SRS, stereotactic radiosurgery; KPS, Karnofsky performance status; RPA, recursive partitioning analysis; RT, radiotherapy.

Radiation regimen    
 WBRT (n = 91)55234 
 SRS (n = 95)744919.005
Age, y    
 ≤60 (n = 90)714015 
 >60 (n = 96)59328.28
Sex    
 Women (n = 95)754516 
 Men (n = 91)54277.009
KPS    
 70–80 (n = 144)65308 
 90–100 (n = 42)755320.022
Primary tumor    
 Breast cancer (n = 31)93620 
 Lung cancer (n = 69)55357 
 Other tumors (n = 86)492917.039
No of brain metastases    
 1 (n = 98)694014 
 2–3 (n = 88)593310.15
Extracranial metastases    
 No (n = 97)673516 
 Yes (n = 89)63410.17
RPA class    
 Class 1 (n = 66)693512 
 Class 2 (n = 120)623811.58
Interval from tumor diagnosis to RT, mo
 ≤15 (n = 91)60297 
 >15 (n = 95)694315.13
All patients (n = 186)653612 

Local recurrence of the treated brain metastases was observed in 88 patients (47%) after a median interval of 5 months (range, 0–27 months). The potential prognostic factors in relation to LC are summarized in Table 4 (univariate analysis). On univariate analysis, improved LC was significantly associated with SRS (vs WBRT) and female sex. On multivariate analysis, both the radiation regimen (RR, 1.64; 95% CI, 1.32–2.04 [P < .001]) and sex (RR, 1.62; 95% CI, 1.07–2.48 [P = .022]) maintained significance.

Table 4. Results of the Univariate Analysis of Local Control of Treated Metastases
CharacteristicAt 6 mo, %At 12 mo, %At 24 mo, %P
  1. WBRT indicates whole-brain radiotherapy; SRS, stereotactic radiosurgery; KPS, Karnofsky performance status; RPA, recursive partitioning analysis; RT, radiotherapy.

Radiation regimen    
 WBRT (n = 91)57265 
 SRS (n = 95)846434<.001
Age, y    
 <60 (n = 90)754820 
 >60 (n = 96)664215.68
Sex    
 Women (n = 95)805322 
 Men (n = 91)613715.031
KPS    
 70–80 (n = 144)694017 
 90–100 (n = 42)755623.21
Primary tumor    
 Breast cancer (n = 31)93690 
 Lung cancer (n = 69)764210 
 Other tumors (n = 86)593925.27
No. of brain metastases    
 1 (n = 98)764720 
 2–3 (n = 88)654317.22
Extracranial metastases    
 No (n = 97)714321 
 Yes (n = 89)72500.71
RPA class    
 Class 1 (n = 66)734319 
 Class 2 (n = 120)704818.93
Interval from tumor diagnosis to RT, mo
 ≤15 (n = 91)673712 
 >15 (n = 95)755224.19
All patients (n = 186)714519 

An intracerebral recurrence distant of the treated brain metastases was observed in 61 patients (33%) after a median interval of 7 months (range, 0–51 months). The potential prognostic factors in relation to DC are summarized in Table 5 (univariate analysis). On univariate analysis, improved DC was associated significantly with better KPS and absence of extracranial metastases. On multivariate analysis, both KPS (RR, 1.85; 95% CI, 1.00–3.73 [P = .049]) and extracranial metastases (RR, 1.69; 95% CI, 1.01–2.85 [P = .047]) maintained significance.

Table 5. Results of the Univariate Analysis of Brain Control Distant From the Treated Metastases
VariableAt 6 mo, %At 12 mo, %At 24 mo, %P
  1. WBRT indicates whole-brain radiotherapy; SRS, stereotactic radiosurgery; KPS, Karnofsky performance status; RPA, recursive partitioning analysis; RT, radiotherapy.

Radiation regimen    
 WBRT (n = 91)816638 
 SRS (n = 95)826128.80
Age, y    
 ≤60 (n = 90)856632 
 >60 (n = 96)786142.98
Sex    
 Women (n = 95)826632 
 Men (n = 91)816137.98
KPS    
 70–80 (n = 144)785926 
 90–100 (n = 42)927851.029
Primary tumor    
 Breast cancer (n = 31)938026 
 Lung cancer (n = 69)805720 
 Other tumors (n = 86)786455.23
No. of brain metastases    
 1 (n = 98)847237 
 2–3 (n = 88)795531.07
Extracranial metastases    
 No (n = 97)846943 
 Yes (n = 89)795623.019
RPA class    
 Class 1 (n = 66)856739 
 Class 2 (n = 120)796232.38
Interval from tumor diagnosis to RT, mo
 ≤15 (n = 91)805817 
 >15 (n = 95)82 48.11
All patients (n = 186)816435 

The subgroup analyses of each of the 2 RPA classes demonstrated that SRS was associated with significantly better BC and LC compared with WBRT both for patients in RPA Class 1 and for patients in RPA Class 2. OS and DC were not significantly better with SRS than with WBRT. These results are summarized in Table 6.

Table 6. Subgroup Analyses of the 2 Recursive Partitioning Analysis Classes for Survival, Entire Brain Control, Local Control, and Brain Control Distant From Treated Metastases: Potential Impact of the Treatment Schedule
SubgroupAt 6 mo, %At 12 mo, %At 24 mo, %P
  1. OS indicates overall survival; RPA, recursive partitioning analysis; WBRT, whole-brain radiotherapy; SRS, stereotactic radiosurgery; BC, brain control (entire brain control); LC, local control; DC, distant control (brain control from treated metastasis).

OS    
 RPA Class 1    
  WBRT (n = 31)795021 
  SRS (n = 35)866626.33
 RPA Class 2    
  WBRT (n = 60)48227 
  SRS (n = 60)584616.09
BC    
 RPA Class 1    
  WBRT (n = 31)57245 
  SRS (n = 35)814519.047
 RPA Class 2    
  WBRT (n = 60)54220 
  SRS (n = 60)705420.049
LC    
 RPA Class 1    
  WBRT (n = 31)60265 
  SRS (n = 35)845931.003
 RPA Class 2    
  WBRT (n = 60)56270 
  SRS (n = 60)857138<.001
DC    
 RPA Class 1    
  WBRT (n = 31)876742 
  SRS (n = 35)836730.75
 RPA Class 2    
  WBRT (n = 60)776636 
  SRS (n = 60)825527.98

The rates of grade ≥3 acute toxicity according to the Common Toxicity Criteria were 4% in Group A and 2% in Group B. The rates of grade ≥3 late toxicity according to RTOG criteria were 4% for both groups.

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

WBRT is the most common treatment modality for patients with multiple brain metastases. Patients in RPA Classes 1 and 2 who have a limited number of metastases have a considerably better survival than patients who have multiple lesions. Therefore, these patients may benefit from more aggressive treatment, such as surgical resection or SRS.3, 4 However, in a considerable proportion of these patients, resection cannot be performed safely, because the lesions are surgically inaccessible. These patients need to be treated with radiotherapeutic options, such as WBRT and SRS. However, SRS is not available in many centers worldwide, and WBRT often remains the only alternative. In most centers, the standard fractionation of WBRT is 30 Gy in 10 fractions given in 2 weeks (10 fractions of 3 Gy each). Another common schedule in Germany and other European countries is 40 Gy in 20 fractions given in 4 weeks (20 fractions of 2 Gy each). The biologic effect of a radiation schedule depends on total dose and dose per fraction. Different radiation schedules can be compared with the equivalent dose in 2 Gy fractions (EQD2),15 which takes into account both total dose and dose per fraction. The EQD2 is calculated with the equation EQD2 = D × ([d + α/β]/2 Gy + α/β), This is derived from the linear-quadratic model, in which D indicates the total dose, d indicates the dose per fraction, α is the linear (first-order dose-dependent) component of cell killing, β is the quadratic (second-order dose-dependent) component of cell killing, and the α/β ratio is the dose at which both components of cell killing are equal. Assuming an α/β ratio of 10 Gy for tumor cell kill, the EQD2 is 32.5 Gy for 10 fractions of 3 Gy each and 40 Gy for 20 fractions of 2 Gy each.

It is possible to speculate whether WBRT with an EQD2 of 32 Gy or 40 Gy is sufficient to achieve appropriate long-term control and survival in patients with 1 to 3 brain metastases and whether the results can be improved with an escalation of the radiation dose. It has been demonstrated that adding an SRS boost to WBRT results in better LC than WBRT alone.7–9, 16 Other ways to escalate the dose include using greater doses of WBRT, WBRT plus a boost to the metastatic site, or SRS alone. For 18 Gy to 25 Gy of SRS, the EQD2 ranges between 42 Gy and 73 Gy.

Investigators have suggested that, if SRS is administered, then WBRT can be omitted in patients with a limited number of brain metastases, because median survival is not altered significantly with the combined approach.10–12 One prospective study suggested that only in favorable subsets of patients, such as patients in RPA Class 1 or patients with favorable histology,9 WBRT improves survival when added to SRS. Thus, SRS alone can be considered an effective treatment for most patients with 1 to 3 lesions. The current analysis was performed to determine whether SRS alone is superior in terms of survival and brain control compared with WBRT alone in patients with 1 to 3 brain metastases.

Although several studies have compared WBRT alone versus WBRT plus an SRS boost, studies comparing WBRT alone and SRS alone are lacking. Only 1 abstract could be identified.8 Chougule et al. observed no significant difference in median survival between WBRT alone and SRS alone in a series of 67 patients who had 1 to 3 lesions (P value not stated). The 1-year rates of brain control in their study were 87% after SRS and 62% after WBRT. Although LC appeared much better after SRS, a P value for brain control was not stated in that abstract.

In our study, SRS was associated with significantly better LC and BC in both univariate and multivariate analyses. SRS was not associated with significantly better survival in the current series, a result that is in accordance with the findings of Chougule et al.8 However, it is difficult to compare both studies, because we do not know the details of the selection criteria for the study by Chougule et al. It is possible that patients in RPA Class 3 were included in that study, and it is known that those patients have a poor survival regardless of the type of treatment. In the current study, both treatment groups were balanced for the other potential prognostic factors, which reduced the risk of a selection bias. However, the retrospective design of the current study must be taken into account when interpreting these results. Thus, further prospective studies are required to define better the optimal radiation regimen for patients with 1 to 3 brain metastases. In the subgroup analyses performed for patients in RPA Classes 1 and 2 separately, the results were similar to the findings for the entire cohort. Patients in either RPA class appeared to benefit from SRS in terms of BC and LC, whereas survival did not differ significantly.

In the current study, survival was associated significantly with age, KPS, and extracranial metastases, along with RPA class, which takes into account all 3 factors. These findings are in accordance with data regarding the survival of patients with brain metastases presented by Gaspar et al.13 In that study, age, KPS, and lack of extracranial metastases were significant on both univariate analysis and RPA. In their RPA, it was demonstrated that RPA class also retained its prognostic value for patients who underwent SRS.17 Weltman et al. presented a score index for predicting the survival prognosis for patients who underwent SRS for brain metastases.4 Those authors observed that KPS, extracranial metastases, and RPA class were correlated with survival, in accordance with our current results.

To our knowledge, there are nearly no data regarding prognostic factors for BC and LC. A MEDLINE search for prognostic factors regarding BC, LC, and DC for patients with brain metastases revealed 100 references. However, only the study by Kim et al. included a multivariate analysis for LC.18 The multivariate analysis was performed in a series of 53 patients who underwent γ-knife radiosurgery. Only tumor size, which was not assessed in the current study (because only patients with lesions that measured ≤4 cm were included), was significant. In our study, only the treatment regimen and sex were associated with significantly better LC. Other potential prognostic factors were not significant for LC, in accordance with the findings of Kim et al.18 In the current study, KPS and extracranial metastases were significant for DC. Both a poor KPS and the presence of extracranial metastases were indicators of an advanced stage of disease, which is more likely to be associated with new brain metastases, particularly in previously untreated areas of the brain.

Our data demonstrate that SRS alone is associated with improved BC and LC compared with 30 to 40 Gy of WBRT alone for patients in RPA Classes 1 and 2 who have 1 to 3 brain metastases, whereas OS and DS do not differ significantly. The finding that SRS results in better BC can be explained by the finding that more patients had local recurrence of the treated metastases alone than new metastases distant from the treated lesions. According to the available literature, the probability of developing new brain metastases outside the area treated with SRS can be reduced further with the addition of WBRT to SRS, in which survival is not altered.6, 8, 11, 17, 19 Aoyama et al. presented a randomized trial of 132 patients who had 1 to 4 brain metastases and received either WBRT plus SRS or SRS alone.19 The median survival and the 1-year actuarial survival rates were 7.5 months and 39%, respectively, in the WBRT plus SRS group and 8 months and 28%, respectively, in the SRS alone group (P = .42). The 1-year brain tumor recurrence rates were 47% and 76%, respectively (P < .001). Taking into account these data from the literature, SRS should be supplemented by WBRT, particularly in patients who have a relatively favorable survival prognosis, because brain control becomes more of an issue in long-term survivors.

In conclusion, SRS alone appears to be more effective than WBRT alone. Furthermore, it is less time consuming: SRS takes only 1 day, which means that the patients have to spend only very little time of their limited life span receiving treatment.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES
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    Sundstrom JT,Minn H,Lertola KK,Nordman E. Prognosis of patients treated for intracranial metastases with whole-brain irradiation. Ann Med. 1998; 30: 296299.
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    Nieder C,Nestle U,Motaref B,Walter K,Niewald M,Schable K. Prognostic factors in brain metastases: should patients be selected for aggressive treatment according to recursive partitioning analysis (RPA) classes? Int J Radiat Oncol Biol Phys. 2000; 46: 297302.
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    Weltman E,Salvajoli JV,Brandt RA, et al. Radiosurgery for brain metastases: a score index for predicting prognosis. Int J Radiat Oncol Biol Phys. 2000; 46: 11551161.
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    O'Neill BP,Iturria NJ,Link MJ,Pollock BE,Ballman KV,O'Fallon JR. A comparison of surgical resection and stereotactic radiosurgery in the treatment of solitary brain metastases. Int J Radiat Oncol Biol Phys. 2003; 55: 11691176.
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    Pirzkall A,Debus J,Lohr F, et al. Radiosurgery alone or in combination with whole-brain radiotherapy for brain metastases. J Clin Oncol. 1998; 16: 35633569.
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    Kondziolka D,Patel A,Lunsford LD,Kassam A.Flickinger JC. Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys. 1999; 45: 427434.
  • 8
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