Whole-Brain Radiotherapy with 20 Gy in 5 Fractions for Brain Metastases in Patients with Cancer of Unknown Primary (CUP)

BACKGROUND: Whole brain radiotherapy (WBRT) is the most common treatment for brain metastases. Survival of patients with cancer of unknown primary (CUP) presenting with brain metastases is extremely poor. A radiation program with a short overall treatment time (short-course RT) would be preferable to longer programs if it provides similar outcomes. This study compares short-course RT with 20 Gy in 5 fractions (5 x 4 Gy) given over 5 days to longer programs in CUP patients. PATIENTS AND METHODS: Data regarding 101 CUP patients who received either short course WBRT (n=34) with 5 x 4 Gy or long-course WBRT (n=67) with 10 x 3 Gy given over 2 weeks or 20 x 2 Gy given over 4 weeks for brain metastases were analyzed retrospectively. Six additional potential prognostic factors were investigated: age, gender, Karnofsky performance score (KPS), number of brain metastases, extracranial metastases, RPA-(Recursive Partitioning Analysis-)class. RESULTS: On univariate analysis, the radiation program was not associated with survival (p=0.88) nor intracerebral control (p=0.36). Improved survival was associated with KPS >or= 70 (p<0.001), absence of extracranial metastases (p<0.001), and RPA-class 1 (p<0.001). On multivariate analyses, KPS (risk ratio [RR]: 4.55; p<0.001), extracranial metastases (RR: 1.70; p=0.018), and RPA-class (RR: 2.86; p<0.001) maintained significance. On univariate analysis, KPS (p<0.001) and RPA-class (p<0.001) were significantly associated with intracerebral control. On multivariate analyses, KPS (RR: 2.72; p<0.001) and RPA-class (RR: 2.09; p<0.001) remained significant. CONCLUSION: Short-course WBRT with 5 x 4 Gy provided similar intracerebral control and survival as longer programs for the treatment of brain metastases in CUP patients. 5 x 4 Gy appears preferable because it is more convenient for patients.     

Linac Radiosurgery Versus Whole Brain Radiotherapy for Brain Metastases

BACKGROUND AND PURPOSE: For patients with inoperable brain metastases, whole brain radiotherapy (WBRT) has been the standard treatment for decades. Radiosurgery is an effective alternative strategy, but has failed to show a substantial survival benefit so far. The prognostic factors derived from the RTOG recursive partitioning analysis (RPA) provide a framework that allows a nonrandomized comparison of the two modalities. PATIENTS AND METHODS: From 1991 to 1998, 117 patients with one to three previously untreated cerebral metastases underwent single-dose linac radiosurgery (median dose 20 Gy) without adjuvant WBRT. After radiosurgery, 26/117 patients (22%) had salvage WBRT, radiosurgery or neurosurgical resection of recurrent (4/117) and/or new (24/117) metastases. Survival of these patients was compared to a historical group of 138 patients with one to three lesions treated by WBRT (30-36 Gy/3-Gy fractions) from 1978 to 1991; only nine of these patients (7%) had salvage WBRT. All patients were classified into the three RPA prognostic classes based on age, performance score, and presence of extracranial tumor manifestations. RESULTS: In RPA class I (Karnofsky performance score > or = 70, primary tumor controlled, no other metastases, age < 65 years), radiosurgery resulted in a median survival of 25.4 months (n = 23, confidence interval [CI] 5.8-45.0) which was significantly longer than for WBRT (n = 9, 4.7 months, CI 3.8-5.5; p < 0.0001). In RPA class III (Karnofsky performance score < 70), no significant difference in survival between radiosurgery (n = 20, 4.2 months, CI 3.2-5.3) and WBRT (n = 68, 2.5 months, CI 2.2-2.8) was found. In RPA class II (all other patients), radiosurgery produced a small, but significant survival advantage (radiosurgery: n = 74, 5.9 months, CI 3.2-8.5, WBRT: n = 61, 4.1 months, CI 3.4-4.9; p < 0.04). CONCLUSION: Radiosurgery in patients with one to three cerebral metastases results in a substantial survival benefit only in younger patients with a low systemic tumor burden when compared to WBRT alone. It cannot be excluded that this effect is partially caused by the available salvage options after radiosurgery.     

Recursive Partitioning Analysis (RPA) Class Does Not Predict Survival in Patients with Four or More Brain Metastases

BACKGROUND: We evaluated prognostic factors for survival in patients with four or more brain metastases in order to determine whether intense local treatment might be justified for some of them. If up to three brain metastases are present, surgical resection or radiosurgery are currently being considered in case of favorable prognostic factors. PATIENTS AND METHODS: Retrospective intention-to-treat analysis of 113 patients who underwent whole-brain radiotherapy without surgical resection or radiosurgery at a single institution. Standard treatment was given with ten fractions of 3 Gy. Higher total doses were administered in 13% of patients. Recursive partitioning analysis (RPA) prognostic classes have been described by the Radiation Therapy Oncology Group (RTOG) in 1997 (class I: Karnofsky performance status [KPS] > or = 70%, age < or = 65 years, no extracranial metastases, controlled primary tumor; class III: KPS < 70%; class II: others). RESULTS: Median number of brain metastases was six (four to 50). Most patients (69%) had extracranial metastases as well. Criteria of RPA Class I (II) were met in 4% (41%), whereas 56% had KPS < 70% and thus were grouped into class III (Tables 1 and 2). Complete or partial remission of brain metastases was found in 46% of patients who underwent computed tomography. Median survival was 4 months, 1-years survival rate 15%. Only age was a borderline significant prognostic factor in univariate analysis (< or = 50 years vs > 50 years, p = 0.05). Strong trends were found for KPS, extracranial metastases, control of the primary tumor, and breast primary tumor. Number of brain metastases, RPA class and treatment-related factors such as total dose or remission of brain metastases had no appreciable influence on survival (Figure 1). Multivariate analysis failed to identify any significant prognostic factor. CONCLUSIONS: Patients with four or more brain metastases seem to represent a group with unfavorable prognosis where remission of brain metastases or administration of more than 30 Gy were not associated with increased survival. The number of patients in RPA class I was too small to draw final conclusions. However, there was absolutely no survival difference between patients in class II (median survival 3.6 months) and III (median 4.2 months).     

Brain metastasis from non-small cell lung cancer (NSCLC)

Background and purpose

This study investigated the potential prognostic value of the number of involved extracranial organs in patients with brain metastasis from non-small cell lung cancer (NSCLC).

Material and methods

A total of 472 patients who received whole-brain radiotherapy (WBRT) alone with 5?×?4 Gy or 10?×?3 Gy for brain metastasis from NSCLC were included in this retrospective study. In addition to the number of involved extracranial organs, 6 further potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), number of brain metastases, and the interval from cancer diagnosis to WBRT. Subgroup analyses were performed for patients with metastatic involvement of one (lung vs. bone vs. other metastasis) and two (lung?+?bone vs. lung?+?lymph nodes vs. other combinations) extracranial organs.

Results

The survival rates at 6 months of the patients with involvement of 0, 1, 2, 3, and ≥?4 extracranial organs were 52, 27, 17, 4, and 14?%, respectively (p?<?0.001). On multivariate analysis, the number of involved extracranial organs remained significant (risk ratio 1.32; 95?% confidence interval 1.19–1.46; p?<?0.001). Age <?65 years (p?=?0.004), KPS ≥?70 (p?<?0.001), and only 1–3 brain metastases (p?=?0.022) were also significantly associated with survival in the multivariate analysis. In the separate analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the pattern of extracranial organ involvement.

Conclusion

The number of involved extracranial organs is an independent prognostic factor of survival in patients with brain metastasis from NSCLC, irrespective of the pattern of extracranial organ involvement.     

Comparison of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus a stereotactic boost (WBRT + SRS) for one to three brain metastases

Background

The best available treatment of patients with one to three brain metastases is still unclear. This study compared the results of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus SRS (WBRT + SRS).

Patients and Methods

Survival (OS), intracerebral control (IC), and local control of treated metastases (LC) were retrospectively analyzed in 144 patients receiving SRS alone (n = 93) or WBRT + SRS (n = 51). Eight additional potential prognostic factors were evaluated: age, gender, Eastern Cooperative Oncology Group performance score (ECOG-PS), tumor type, number of brain metastases, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from tumor diagnosis to irradiation. Subgroup analyses were performed for RPA class I and II patients.

Results

1-year-OS was 53% after SRS and 56% after WBRT + SRS (p = 0.24). 1-year-IC rates were 51% and 66% (p = 0.015), respectively. 1-year-LC rates were 66% and 87% (p = 0.003), respectively. On multivariate analyses, OS was associated with age (p = 0.004), ECOG-PS (p = 0.005), extracerebral metastases (p < 0.001), RPA class (p < 0.001), and interval from tumor diagnosis to irradiation (p < 0.001). IC was associated with interval from tumor diagnosis to irradiation (p = 0.004) and almost with treatment (p = 0.09), and LC with treatment (p = 0.026) and almost with interval (p = 0.08). The results of the subgroup analyses were similar to those of the entire cohort. The increase in IC was stronger in RPA class I patients.

Conclusion

WBRT + SRS resulted in better IC and LC but not better OS than SRS alone. Because also IC and LC are important end-points, additional WBRT appears justified in patients with one to three brain metastases, in particular in RPA class I patients.     

Recursive Partitioning Analysis (RPA) Class Does Not Predict Survival in Patients with Four or More Brain Metastases

Background: We evaluated prognostic factors for survival in patients with four or more brain metastases in order to determine whether intense local treatment might be justified for some of them. If up to three brain metastases are present, surgical resection or radiosurgery are currently being considered in case of favorable prognostic factors. Patients and Methods: Retrospective intention-to-treat analysis of 113 patients who underwent whole-brain radiotherapy without surgical resection or radiosurgery at a single institution. Standard treatment was given with ten fractions of 3 Gy. Higher total doses were administered in 13% of patients. Recursive partitioning analysis (RPA) prognostic classes have been described by the Radiation Therapy Oncology Group (RTOG) in 1997 (class I: Karnofsky performance status [KPS] S 70%, age h 65 years, no extracranial metastases, controlled primary tumor; class III: KPS < 70%; class II: others). Results: Median number of brain metastases was six (four to 50). Most patients (69%) had extracranial metastases as well. Criteria of RPA Class I (II) were met in 4% (41%), whereas 56% had KPS < 70% and thus were grouped into class III (Tables 1 and 2). Complete or partial remission of brain metastases was found in 46% of patients who underwent computed tomography. Median survival was 4 months, 1-years survival rate 15%. Only age was a borderline significant prognostic factor in univariate analysis (h 50 years vs > 50 years, p = 0.05). Strong trends were found for KPS, extracranial metastases, control of the primary tumor, and breast primary tumor. Number of brain metastases, RPA class and treatment-related factors such as total dose or remission of brain metastases had no appreciable influence on survival (Figure 1). Multivariate analysis failed to identify any significant prognostic factor. Conclusions: Patients with four or more brain metastases seem to represent a group with unfavorable prognosis where remission of brain metastases or administration of more than 30 Gy were not associated with increased survival. The number of patients in RPA class I was too small to draw final conclusions. However, there was absolutely no survival difference between patients in class II (median survival 3.6 months) and III (median 4.2 months). Hintergrund: Die Prognosefaktoren für Patienten mit vier oder mehr Hirnmetastasen wurden ausgewertet, um festzulegen, ob einige dieser Patienten eine intensivierte Lokalbehandlung erhalten sollten. Bei Vorliegen von bis zu drei Hirnmetastasen wird gegenwärtig im Fall günstiger Prognoseparameter eine Resektion oder Radiochirurgie erwogen. Patienten und Methoden: Retrospektive Analyse (Intention-to-Treat) von 113 Patienten, die an einer einzigen Klinik mittels Ganzhirnbestrahlung ohne Resektion oder Radiochirurgie behandelt wurden. Die Standardtherapie erfolgte mit zehn Fraktionen von 3 Gy. 13% der Patienten erhielten eine höhere Gesamtdosis. Die Radiation Therapy Oncology Group (RTOG) publizierte 1997 einen prognostischen Score, der auf der Basis einer rekursiven Partitionierungsanalyse (RPA) ermittelt wurde. Die Kriterien für Klasse I lauten: Karnofsky-Index (KPS) S 70%, Alter h 65 Jahre, keine extrakraniellen Metastasen, kontrollierter Primärtumor; Klasse III: KPS < 70%; Klasse II: andere. Ergebnisse: Im Median lagen sechs Hirnmetastasen vor (vier bis 50). 69% der Patienten hatten auch extrakranielle Metastasen. Die Kriterien für Klasse I bzw. Klasse II erfüllten 4% bzw. 41%, wohingegen 56% wegen des schlechten Allgemeinzustands in Klasse III gruppiert werden (Tabellen 1 und 2). Eine komplette oder partielle Remission der Hirnmetasasen wurde bei 46% der Patienten, die computertomographisch nachuntersucht worden waren, festgestellt. Das mediane Überleben betrug 4 Monate (1-Jahres-Überlebensrate 15%). Lediglich das Alter konnte als grenzwertig signifikanter Prognosefaktor identifiziert werden (h 50 Jahre vs. > 50 Jahre, p = 0,05). Tendenzen ergaben sich auch für KPS, extrakranielle Metastasen, kontrollierten Primärtumor und Mammakarzinome. Die Zahl der Hirnmetastasen, RPA-Klasse, Ansprechen der Hirnmetastasen und Bestrahlungsdosis hatten keinen erkennbaren Einfluss auf das Überleben (Abbildung 1). Multivariat konnten keine signifikanten Faktoren herausgearbeitet werden. Schlussfolgerung: Patienten mit vier oder mehr Hirnmetastasen scheinen eine Subgruppe mit ungünstiger Prognose zu repräsentieren, bei denen ein Ansprechen der Metastasen oder eine höher dosierte Strahlentherapie das Überleben nicht verbesserten. Die Zahl der Patienten in RPA-Klasse I war zu gering für definitive Schlussfolgerungen. Es ergab sich keine signifikante Differenz im Überleben zwischen Klasse II und III (medianes Überleben 3,6 vs. 4,2 Monate).     

Brain metastasis

Background and purpose

This study was performed to evaluate the prognostic role for survival of the number and the type of involved extracranial organs in patients with brain metastasis.

Material and methods

The data of 1146 patients who received whole-brain radiotherapy (WBRT) alone for brain metastasis have been retrospectively analyzed. In addition to the number of involved extra cranial organs, seven potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), primary tumor type, number of brain metastases, and the interval from cancer diagnosis to WBRT. Additionally, subgroup analyses were performed for patients with involvement of one (lung vs. bone vs. liver vs. other metastasis) and two (lung + lymph nodes vs. lung + bone vs. lung + liver vs. liver + bone vs. other combinations) extracranial organs.

Results

The 6-month survival rates for the involvement of 0, 1, 2, 3, and ≥?4 extracranial organs were 51, 30, 16, 13, and 10?%, respectively (p?<?0.001). On multivariate analysis, the number of involved extracranial organs maintained significance (risk ratio 1.26; 95?% confidence interval 1.18–1.34; p?<?0.001). According to the multivariate analysis, age (p?<?0.001), gender (p?=?0.002), and KPS (p?<?0.001) were also independent prognostic factors for survival. In the subgroup analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the extracranial organ involved.

Conclusion

The number of involved extracranial organs proved to be an independent prognostic factor in patients with brain metastasis, regardless of the organs involved. The number of involved extracranial organs should be considered in future trials designed for patients with brain metastasis.     

Treatment of Solitary Brain Metastasis

BACKGROUND: Whole brain radiation therapy (WBRT) is reported to improve local control after resection of brain metastases. Improvement of survival was only observed in patients with controlled extracranial disease. The optimum radiation schedule has yet to be defined. The authors' experience with a postoperative approach including WBRT and a radiation boost to the metastatic site is presented. PATIENTS AND METHODS: Criteria for inclusion into this retrospective analysis were solitary brain metastasis, Karnofsky performance status > or = 70%, and controlled extracranial disease. Two therapies were compared for local control and survival: surgery followed by 40 Gy WBRT (group A) versus surgery followed by 40 Gy WBRT and a 10 Gy boost (group B). Statistical analysis was performed using the Kaplan-Meier method and log-rank test. RESULTS: 33 patients were included (17 group A, 16 group B). The results suggested better local control (p = 0.0087) and survival (p = 0.0023) for group B. 17/17 patients (100%) of group A and 13/16 patients (81%) of group B showed progression of brain metastasis, 8/17 and 3/16 patients in the area of metastatic surgery. Median time to progression was 7 (1-22) months in group A and 12 (3-42) months in group B. The number of cancer-related deaths amounted to 17/17 (100%) in group A after a median interval of 9 (3-26) months, and to 9/16 (56%) in group B after 14 (4-46) months. CONCLUSION: After resection of solitary brain metastasis, a radiation boost in addition to WBRT seems to improve local control and survival when compared to postoperative WBRT alone. The results should be confirmed in a larger prospective trial.     

Prognostic Factors for Brain Metastases after Whole Brain Radiotherapy

PURPOSE: Prognostic factors for overall survival of patients treated for brain metastases with whole brain radiotherapy (WBRT) at a single institution were retrospectively evaluated, and the validity of the RTOG recursive partitioning analysis (RPA) for prognostic classes was assessed. PATIENTS AND METHODS: The data of all patients (n = 268) with brain metastases from solid tumors homogeneously treated between 01/1997 and 09/1999 at the University of Heidelberg, Germany, with WBRT without surgery or radiosurgery were reviewed. 13 different patient- and therapy-related variables were evaluated for prognosis. Second, a grouping of the study cohort was performed according to the RTOG RPA prognostic classes. RESULTS: Median survival of the whole population after the start of WBRT was 3.8 months. The 1-year survival rate was 19%. Multivariate analysis revealed that only the Karnofsky performance status, control of the primary and no extracranial disease were independent prognostic factors for overall survival. These are also the main determinants of the RTOG RPA classes. Applying the RTOG RPA classes to the authors' data set revealed three subgroups with significantly different prognosis. CONCLUSION: Based on this analysis, prognostic factors for survival after WBRT in patients with brain metastases could be identified. A total of 19% (n = 44/232) survived > or = 1 year, whereas overall survival was poor. The potential value of the RPA classes in estimating the patient's prognosis could be confirmed.     

A New Scoring System to Predicting the Survival of Patients Treated with Whole-Brain Radiotherapy for Brain Metastases

PURPOSE: To create a scoring system to estimate survival of patients who received whole-brain radiotherapy (WBRT) for brain metastases. MATERIAL AND METHODS: Based on a multivariate analysis of 1,085 retrospectively analyzed patients, a scoring system was developed. This score was based on the four significant prognostic factors found in the multivariate analysis including: age, performance status, extracranial metastases at the time of WBRT, and interval between tumor diagnosis and WBRT. The score for each prognostic factor was determined by dividing the 6-month survival rate (in %) by 10. The total score represented the sum of the partial scores for each prognostic factor. Total scores ranged from 9 to 18 points, and patients were divided into four groups. For each group, survival was compared for short-course (5 x 4 Gy) versus longer-course WBRT (10 x 3 Gy/20 x 2 Gy). RESULTS: Actuarial 6-month survival rates were 6% for patients with scores of 9-10 points, 15% for those with scores of 11-13 points, 43% for those with scores of 14-16 points, and 76% for those with scores of 17-18 points (p < 0.001). Longer-course WBRT was not associated with better survival than short-course WBRT in any of the four groups. CONCLUSION: Patients with brain metastases receiving WBRT can be grouped with this score to estimate survival. Short-course and longer-course WBRT resulted in similar survival in all groups studied. However, in the more favorable patients with scores of 17-18, longer-course WBRT with lower doses per fraction should be considered, as these schedules have been associated with less neurocognitive toxicity.     

The impact of tumour histology and recursive partitioning analysis classification on the prognosis of patients treated with whole-brain hypofractionated radiotherapy for brain metastases: analysis of 382 patients

Purpose

Recursive partitioning analysis (RPA) is a prognostic index capable of predicting survival in patients with brain metastases. Histology of the primary tumour has only recently been introduced among the factors that could potentially affect the prognosis of these patients. The main purpose of this study was to analyse the impact of RPA in correlation with histology of the primary tumour in patients with brain metastases treated with hypofractionated radiotherapy.

Materials and methods

A total of 382 patients were treated at the Department of Radiotherapy of Brescia University, and RPA classes were retrospectively assigned to all patients. Univariate and multivariate analyses were then performed to verify the role of the single prognostic variables, for the entire group and for each prognostic class, as well as in correlation with histology of the primary tumour.

Results

Most patients were classified as RPA prognostic class 2 (48%). The majority of patients was treated with a total dose of 30 Gy delivered in ten fractions, whereas the dose of 20 Gy in four or five fractions was primarily used in patients classified as RPA class 3. At univariate analysis, the main variable correlating with overall survival (OS) was RPA class (p=0.000). Uni- and multivariate analysis performed on RPA class 1 patients only confirmed the role of general performance status, number of metastases and total radiotherapy dose for predicting OS. In the group with the worst prognosis (RPA class 3), none of the variables had a statistically significant role in improving OS. Tumour histology and radiotherapy dose influence OS, even in RPA class 1 and 2 patients.

Conclusions

This analysis confirms that RPA prognostic class is the factor that most predicts survival. Primary tumour histology helps determine prognosis, especially in RPA prognostic classes 1 and 2. As regards RPA class 3, no factor influences survival prognosis.     

Phase I/II Trial of Simultaneous Whole-Brain Irradiation and Dose-Escalating Topotecan for Brain Metastases

BACKGROUND AND PURPOSE: Topotecan penetrates the blood-brain barrier and sensitizes tumor cells against radiation. A phase I/II dose-escalating trial of repetitive daily i. v. topotecan application simultaneously with whole-brain irradiation (WBRT) was conducted to estimate toxicity, maximum tolerated dose and survival in patients with inoperable brain metastases. PATIENTS AND METHODS: In 47 patients suffering from previously untreated brain metastases, topotecan was applied on a daily i. v. schedule simultaneously with WBRT (36 Gy/3-Gy fractions). The infusion schedule started at the beginning of WBRT and was discontinued during weekends. Each infusion was completed within 1-2 h before irradiation. In a dose-finding study, topotecan was escalated from 5 x 0.5 mg/m(2), 8 x 0.5 mg/m(2), 12 x 0.5 mg/m(2) to 12 x 0.6 mg/m(2). RESULTS: Altogether, 38/47 patients (81%) completed the prescribed schedule. Leukopenia and thrombocytopenia were dose-limiting. Grade 3/4 hematologic toxicity occurred in 5/32 chemona?ve patients (16%) and 7/15 patients (47%) with previous chemotherapy. At 12 x 0.6 mg/m(2), 2/4 patients experienced grade 4 leukopenia/thrombopenia. Nonhematologic toxicities were generally mild to moderate and unrelated to topotecan. Response evaluation was possible in 26/47 patients, overall response rate was 58% (CR [complete remission] 5/26, PR [partial remission] 10/26, NC [no change] 8/26). Median survival amounted to 5.1 months. In 15/42 patients (36%), brain metastases were the dominant cause of death. CONCLUSION: For a daily topotecan schedule simultaneous to WBRT, the maximum tolerated dose is 12 x 0.5 mg/m(2) in chemona?ve patients. For chemo-pretreated patients, daily doses should be reduced to 0.4 mg/m(2). A phase III trial has now been started to find out whether WBRT + topotecan increases survival compared to WBRT alone.     

Efficacy of whole brain radiotherapy combined with fractionated stereotactic radiotherapy in metastatic brain tumors, and prognostic factors

PURPOSE: We attempted to analyze the effectiveness of whole brain radiotherapy (WBRT) combined with fractionated stereotactic radiotherapy (FSRT) in brain metastases. METHODS: Thirty-seven metastatic brain tumors in 29 patients without previous treatment were treated with WBRT plus FSRT, from October 1996 to February 2002. Four of the patients received stereotactic radiosurgery (SRS) prior to WBRT. Non-small cell lung cancer was the most common type of primary tumor (20/29). The total dose to the whole brain ranged from 30 Gy to 40 Gy, and the boost dose from FSRT ranged from 12 Gy to 40 Gy. End points were survival rate and local control rates. Factors influencing survival were evaluated. RESULTS: Median survival was 13 months, and actuarial survival rates at one and two years were 81% and 39%, respectively. Actuarial one and two year local control rates for all lesions were 78% and 71%, respectively. Survival was significantly associated with age, tumor size, presence of active extracranial tumors, and performance status. No acute or delayed complications were observed. CONCLUSIONS: We believe that WBRT plus FSRT should be included in the treatment options for metastatic brain tumors, and we consider the effect of this non-invasive method to be quite good in patients with good prognostic factors, although other invasive modalities could also be effective in them.     

Predicting the presence of extracranial metastases in patients with brain metastases upon first diagnosis of cancer

Background and purpose

This study aimed to determine factors allowing the prediction of extracranial metastases in patients presenting with brain metastases at the first diagnosis of cancer.

Materials and methods

Data from 659 patients with brain metastases upon first diagnosis of cancer were retrospectively analyzed. The parameters age, gender, Karnofsky performance score (KPS), primary tumor type and number of brain metastases were compared between 359 patients with extracranial metastases and 300 patients without extracranial metastases. Additional analyses were performed for patients with the most unfavorable and those with the most favorable characteristics.

Results

The comparison of patients with versus without extracranial metastases revealed significant differences between the groups in terms of KPS (p?<?0.001) and number of brain metastases (p?<?0.001). Of the study patients, 113 had both most unfavorable characteristics, i.e. KPS ≤?50 and ≥?4 brain metastases. The sensitivity for identifying patients with extracranial metastases was 82?%; specificity was 51?%. A total of 50 patients had KPS ≥?90 and only one brain metastasis. The sensitivity for identifying patients without extracranial metastases was 86?%; specificity was 58?%.

Conclusion

The combination of KPS and the number of brain metastases can help to predict the presence or absence of extracranial metastases.     

伽玛刀立体定向放疗结合全脑照射治疗脑转移瘤临床效果分析

目的 分析立体定向放疗结合全脑照射治疗脑转移瘤的疗效和预后,同时观察服用替莫唑胺(TMZ)与放疗结合对患者生存率的影响。方法 脑转移瘤患者52例,按照治疗方法不同分为2组,一组为全脑照射(WBRT)+立体定向放疗(SRT,伽玛刀),共35例,一组为单纯SRT,共17例。全脑放疗分次剂量为1.8~3.0 Gy/次,1 次/d,5 次/周,总剂量D_T30~40 Gy,WBRT+SRT组全脑后伽玛刀补量采用45%~75%等剂量曲线包绕PTV,边缘剂量12~15 Gy,中心剂量20~30 Gy。单纯SRT组分次立体定向放疗采用45%~75%等剂量曲线包绕PTV,边缘剂量36~40 Gy,中心剂量70~80 Gy。随访1~2年。所选52例患者中有20例患者放疗期间及放疗后服用替莫唑胺胶囊,同步化疗组化疗方案为:口服替莫唑胺75 mg/m²,1次/d,直至放疗结束,放疗结束后再服用3~6个月,剂量改为150 mg/m²。结果 放射治疗后1~3个月,复查CT/MRI显示总有效率(CR+PR)为84.62%,WBRT+SRT组有效率为88.57%,SRT组有效率为76.47%;肿瘤的6个月及1年的局部控制率分别为92.10%和85.20%。WBRT+SRT组的平均生存期13.2个月,中位生存期11个月;6个月生存率为71.40%,12个月生存率为54.30%,18个月生存率为14.30%。SRT组的平均生存期10.2个月,中位生存期9个月;6个月生存率为41.20%,12个月生存率为23.50%,18个月生存率为5.88%。替莫唑胺+放疗与单纯放疗的6个月、12个月及18个月生存率分别为80.00%和56.30%、60.00%和37.50%、10.00%和12.50%。结论 WBRT+SRT治疗脑转移瘤总体上优于单纯SRT治疗。放疗+TMZ联合治疗与单纯放疗相比,替莫唑胺在放疗过程中服用可提高患者生存率,不良反应无显著增加。     

Stereotactic radiosurgery for newly diagnosed brain metastases

Background and purpose

Three doses were compared for local control of irradiated metastases, freedom from new brain metastases, and survival in patients receiving stereotactic radiosurgery (SRS) alone for one to three newly diagnosed brain metastases.

Patients and methods

In all, 134 patients were assigned to three groups according to the SRS dose given to the margins of the lesions: 13–16 Gy (n?=?33), 18 Gy (n?=?18), and 20 Gy (n?=?83). Additional potential prognostic factors were evaluated: age (≤?60 vs. >?60 years), gender, Karnofsky Performance Scale score (70–80 vs. 90–100), tumor type (non-small-cell lung cancer vs. melanoma vs. others), number of brain metastases (1 vs. 2–3), lesion size (?24 months).

Results

For 13–16 Gy, 18 Gy, and 20 Gy, the 1-year local control rates were 31, 65, and 79?%, respectively (p?p?p?p?=?0.12); 18 Gy showed a strong trend toward better local control when compared with 13–16 Gy (p?=?0.059). Freedom from new brain metastases (p?=?0.57) and survival (p?=?0.15) were not associated with SRS dose in the univariate analysis.

Conclusion

SRS doses of 18 Gy and 20 Gy resulted in better local control than 13–16 Gy. However, 20 Gy and 18 Gy must be compared again in a larger cohort of patients. Freedom from new brain metastases and survival were not associated with SRS dose.     

脑转移瘤立体定向放射治疗进展

MRI在脑转移瘤的诊断、治疗以及随访中有重要作用。原发灶状况、脑转移瘤的体积、立体定向放疗前后是否加全脑放疗、一般状况评分、回归分割分析(RPA)分级、是否存在颅外转移等是影响脑转移瘤治疗效果的主要因素。单纯立体定向放疗逐渐成为脑转移瘤治疗的主流,分次立体定向放疗在脑转移瘤治疗中的作用尚未完全明确。     

Dose escalation of radiotherapy for Metastatic Spinal Cord Compression (MSCC) in patients with relatively favorable survival prognosis

Background and Purpose

Local control of metastatic spinal cord compression (MSCC) is particularly important for long-term survivors. Radiotherapy alone is the most common treatment for MSCC. The most frequently used schedule world wide is 30 Gy/10 fractions. This study investigated whether patients with favorable survival prognoses benefit from a dose escalation beyond 30 Gy.

Patients and Methods

Data from 191 patients treated with 30 Gy/10 fractions were matched to 191 patients (1:1) receiving higher doses (37.5 Gy/15 fractions or 40 Gy/20 fractions). All patients had favorable survival prognoses based on a validated scoring system and were matched for age, gender, tumor type, performance status, number of involved vertebrae, visceral or other bone metastases, interval from tumor diagnosis to radiotherapy, ambulatory status, and time developing motor deficits. Both groups were compared for local control, progression-free survival, overall survival, and functional outcome.

Results

Local control rates at 2 years were 71 % after 30 Gy and 92 % after higher doses (p = 0.012). Two-year progression-free survival rates were 68 % and 90 %, respectively (p = 0.013). Two-year overall survival rates were 53 % and 68 %, respectively (p = 0.032). Results maintained significance in the multivariate analyses (Cox proportional hazards model; stratified model) with respect to local control (p = 0.011; p = 0.012), progression-free survival (p = 0.010; p = 0.018), and overall survival (p = 0.014; p = 0.015). Functional outcome was similar in both groups. Motor function improved in 40 % of patients after 30 Gy and 41 % after higher doses (p = 0.98).

Conclusion

Escalation of the radiation dose beyond 30 Gy resulted in significantly better local control, progression-free survival, and overall survival in patients with favorable survival prognoses.     

Radiation therapy for painful bone metastases; aiming at optimal treatment schedules

PURPOSE: To evaluate the pain relief obtained by radiation therapy for painful bone metastases, with a special regard to general condition. MATERIALS AND METHODS: Between June 1998 and May 2000, 54 patients with 86 painful bone metastases were treated with radiation therapy whose effects could be evaluated for a minimum period of 6 months or until death. Treatment schedules were 3 Gy/fraction/day (30-36 Gy/10-12 fractions) in usual cases (61 lesions), 4-8 Gy/fraction/day (8-20 Gy/1-5 fractions) in patients with a poor general condition (9 lesions), and 2 Gy/fraction/day (40-50 Gy/20-25 fractions) in lesions with a large radiation field (16 lesions). RESULTS: Complete pain relief without medication (CR) was achieved in 40 lesions (47%). Significant predictors for CR were primary site (p = 0.0003), performance status (p = 0.0060), pain score (p = 0.0190), narcotic score (p < 0.0001), and prognosis (p < 0.0001), but no difference was found in CR among treatment schedules. No evidence of severe radiation-induced complication was seen. CONCLUSION: General condition (performance status and prognosis) has an influence on pain relief. Compared with the daily 2 Gy protocol, the daily 3 Gy protocol has the advantage of shorter treatment time. The treatment schedule should be assessed in patients with a large radiation field and/or poor general condition. Especially for the patients with poor general condition, combined pain medication should be considered.