Initial Brain Metastases Research Articles

Abstract P6-11-02: Patient characteristics and outcomes for patients with HER2-overexpressing breast cancer with brain metastases undergoing radiation therapy in the pre- and post adjuvant trastuzumab era

Abstract Background: Trastuzumab (H) has improved outcomes for patients with HER2 overexpressing (HER2+) breast cancer (BC) and thus increased the at-risk period for development of brain metastases (BM). In this study we describe the characteristics and outcomes of patients with HER2+BCBM who underwent stereotactic radiosurgery (SRS) or whole brain radiation (WBRT) as initial BM treatment (tx) in the pre- and the post adjuvant (adj) H era at MSKCC. Methods: 100 consecutive pts with HER2+ BCBM who received SRS or WBRT from January 2001 to December 2011 were identified. Clinical, pathologic and tx information were obtained by retrospective review. Pt characteristics at the time of BM diagnosis (dx) and their associations with time from BM to death were evaluated by Kaplan-Meier (KM) curves, log-rank tests, and Cox proportional hazard models. Results: The median age at BM dx was 54 yrs (range 26-79). 31% and 69% of pts received SRS and WBRT respectively. After the BM dx, 97% continued to receive systemic tx consisting of chemotherapy and/or anti-HER2 tx. 97% of pts received H for MBC and 17% received H in the adj setting (all after 2005). Patient characteristics were compared between pre-adj H (2001-2005) and post-adj H (2006-2011) cohorts. The only significant differences noted between the cohorts in univariate analysis were extra-CNS disease control and use of anti-HER2 therapy after BM dx: pre-adj H era pts had a higher likelihood of extra-CNS disease control (79.5% vs. 52%, p = 0.004) at BM dx and less use of anti-HER2 tx after BM dx (70% vs. 87.5%. p = 0.05). For all pts, the median follow-up for survivors was 33.5 mos (range 18-103). There were 79 deaths. The median survival from BM dx was 19.4 mos (95%CI: 15.5, 26.6). KM curves and log-rank tests showed significantly better survival from BM for pts with higher KPS, single BM, extra-CNS disease control, lack of neurologic sx at BM dx, initial presentation without LMD, use of lapatinib (ever), SRS as initial RT, and use of any anti-HER2 tx after BM dx. Multivariate analysis showed that higher KPS [HR 0.21 (0.09,0.53)], extra-CNS disease control [HR 2.89 (1.67, 5.00)], single BM [HR 4.73 (2.11,10.60)], use of anti-HER2 tx after BM dx [HR 0.30 (0.17,0.53)], asymptomatic status at BM dx [HR 3.69 (1.69,8.07)] were associated with improved survival from BM. Lack of neurologic sx at BM dx was significantly associated with longer survival from BM even after adjustment for other potentially confounding prognostic factors. Conclusion: These data are mostly consistent with prior reports regarding prognostic factors and inform contemporary clinical trial design. In pts with HER2+BCBM where the majority were subsequently exposed to anti-HER2 and other systemic tx, presence of neurologic sx at BM dx was significantly associated with worse survival after BM dx. Prospective evaluation of screening brain MRI allowing for earlier detection, leading to more careful monitoring or pre-emptive tx of asymptomatic BM may be warranted. The observation of better extra-CNS disease control at BM dx among pts in the pre- adj H era was unexpected, is hypothesis generating, and requires independent confirmation. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-11-02.

Comparison of clinical characteristics between patients with ALK-positive and EGFR-positive lung adenocarcinoma

The discovery of the chromosomal fusion product of anaplastic lymphoma kinase (ALK) with echinoderm microtubule-associated protein-like 4 (EML4) (EML4-ALK) has changed the treatment paradigm of lung cancer. In this study, we analysed the clinical characteristics, including bronchoscopic findings, of patients with EML4-ALK-positive adenocarcinoma and compared them with those of EGFR mutation-positive patients. In this retrospective cohort study, the clinical characteristics and bronchoscopic findings of patients with ALK fusion-positive lung cancers were compared to patients with EGFR-mutant lung cancers. Among the 440 patients with adenocarcinoma of lung screened for this study, 46 (10.4%) harboured the EML4-ALK fusion, 90 (20.4%) harboured an activating EGFR mutation, and all had adenocarcinoma. In univariate analysis, ALK-positive patients were significantly younger than EGFR-positive patients (p=0.004) and were more commonly male (p=0.021). An initial status of stage IV metastatic cancer was more frequently noted in EML4-ALK-positive patients (p=0.012), with initial brain metastasis frequently observed (p=0.007). Compared with EGFR-positive patients, EML4-ALK-positive patients were significantly more likely to have positive bronchoscopic findings, which suggested a more centralized origin (p=0.001). EML4-ALK patients also had significantly more positive bronchoscopic findings and were more commonly male in multivariate analysis. The EML4-ALK fusion defines a new molecular subset of NSCLC that has distinct clinical and bronchoscopic findings suggesting more proximal origin when compared to tumours harbouring EGFR mutations.

Survival patterns following brain metastases for patients with melanoma in the targeted therapy era.

9064 Background: Survival from metastatic melanoma (MM) has been significantly prolonged with the introduction of molecularly targeted therapy, including BRAF inhibitors (BRAFi) for patients (pts) with the V600E mutation. Here, we present the first data describing patterns of survival after diagnosis of brain metastases (BM) in a large cohort of these pts with long follow-up. Methods: A retrospective review of 191 MM pts accrued on multiple prospective trials between 2008–2012 was conducted. These trials assessed novel immunologic and targeted therapies in pts with both BRAF mutant (n=70) and wild type/unknown (n=121) tumors. We evaluated pt characteristics and the impact of systemic and BM-directed treatments. Results: Of 98 pts who developed BM, median follow-up after first BM was 7.7 months (15.5 months for the 25 living pts), and 33 were treated with BRAFi. Median duration of BRAFi use was 5.9 months (range 0.7–27.1), which preceded BM in 30%, was concurrent with first BM in 18%, and followed first BM in 52%. Ipilimumab or anti–PD-1/PD-L1 immunotherapy was given to 58% of pts who received a BRAFi and 95% of those who did not. Limited intracranial disease on initial BM presentation (defined as ≤3 lesions) occurred in 70% of BRAFi-treated pts and 74% of non-BRAFi pts, and 70% of BRAFi pts received at least one focal BM treatment (stereotactic radiosurgery or resection) compared to 75% of non-BRAFi pts. As shown in the Table, actuarial survival after BM diagnosis was prolonged among pts treated with a BRAFi. This is due primarily to the nearly 2-year median survival of pts for whom a BRAFi was initiated after BM were diagnosed. Conclusions: Survival for pts with BM from BRAF mutant MM can significantly exceed the often anticipated 4–6 months, particularly if a BRAFi is initiated after BM arise. This supports BRAFi activity in intracranial disease, and helps to inform trials currently under way testing BRAFi use among MM pts with previously diagnosed BM. [Table: see text]

The effect of tumor subtype on the time from primary diagnosis to development of brain metastases and survival in patients with breast cancer

Our group has previously published the Diagnosis-Specific Graded Prognostic Assessment (GPA) showing the prognostic factors associated with survival in patients with brain metastases (BM). The purpose of this study is to investigate the relationship of breast cancer subtype to the time interval from primary diagnosis (PD) to development of BM (TPDBM), number of BM at initial BM presentation and survival. We analyzed our previously described multi-institutional retrospective database of 865 breast cancer patients treated for newly-diagnosed BM from 1993 to 2010. Several factors found to be associated with survival were incorporated into the Breast-GPA, including tumor subtype. The GPA database was further analyzed to determine if the subtype correlated with the TPDBM, number of BM, and survival from PD. After exclusions for incomplete data, 383 patients remained eligible for analysis. The subtypes were approximated as follows: Luminal B: triple positive; HER2: HER2 positive/ER/PR negative; Luminal A; ER/PR positive/HER2 negative; Basal: triple negative. Patients with Basal (90), HER2 (119), Luminal B (98) and Luminal A (76) tumor subtypes had a median TPDBM of 27.5, 35.8, 47.4 and 54.4 months (p < 0.01), median survival from PD of 39.6, 66.4, 90.3 and 72.7 months (p < 0.01) and median survival from BM of 7.3, 17.9, 22.9 and 10.0 months (p < 0.01), respectively. Tumor subtype is an important prognostic factor for survival in patients with breast cancer and BM. Although TPDBM is not an independent prognostic factor for survival (and thus not part of the Breast-GPA), the TPDBM does correlate with tumor subtype but does not correlate with the number of BM. Patients with Basal and HER2 tumor subtypes have short TPDBM. Prospective studies are needed to determine if screening brain MRIs are indicated in patients with Basal or HER2 subtypes.

Brain metastases in patients with urothelial carcinoma.

282 Background: Muscle invasive urothelial cancers are infrequent. Patients (pts) with metastatic disease have poor prognosis. Brain metastases (BM) are rare. The aim of this retrospective study is to analyse the characteristics, the treatment and the evolution of patients with BM treated in a single centre. Methods: Thirty pts with BM were identified among the 1591 pts with urothelial carcinoma seen at the Centre Léon Bérard, between 1994 and 2011. The study population was described, overall survival (OS) from diagnosis of BM was estimated by Kaplan-Meier method and prognostic factors were explored using a Cox model. Results: Twenty seven pts in our series were male. Median age at initial diagnosis was 60 years (range: 33.9-78.9 years). Twenty two pts had primary bladder tumours and 8 upper urinary tract tumours. Twenty four pts underwent surgery for their primary lesion, 2 received chemoradiotherapy and 4 did not receive any radical local treatment. Six pts had metastatic disease at initial presentation: 3 were operated on. Median delay between initial diagnosis and BM was 16.6 months (range: 0-56.4 months), 3 patients had BM at initial presentation. Median time between first metastases and BM was 10 months (range=0-52 months). Eleven patients developed BM as one of the first sites of metastases. BM were symptomatic in 28 pts: specific neurological symptoms (n=25), headaches (n=6), epilepsy (n=2). For the 2 other pts, they were discovered on a systematic brain MRI. Eighteen pts had cerebral metastases only, 5 pts had cerebellar metastases only, 6 had both; the last patient had cerebral, cerebellar and meningeal involvement. Half of the pts had only 1 brain lesion. Five pts were operated on: 4 received postoperative radiotherapy; 19 patients were given radiotherapy alone and 6 did not get any local therapy. In this series, median OS from diagnosis of BM was 3.4 months (IC95% [2.2-10.3]). Only the administration of chemotherapy after the diagnosis of BM was significantly associated with OS; probably because only fit enough patients were offered treatment. Conclusions: Prognosis of patients with urothelial carcinoma and BM is poor; however some patients have long survivals. Treatment is not codified as there is little data in the literature.

Abstract P3-12-02: The impact of estrogen receptor status on treatment outcomes following gamma knife radiosurgery for brain metastases of primary breast cancer

Abstract INTRODUCTION: Estrogen receptor (ER) status is a critical component of determining initial therapy of newly diagnosed breast cancer. Although 70% of primary breast malignancies are ER+, there remains limited data on whether ER status influences treatment outcomes for patients with brain metastases. Gamma Knife Radiosurgery (GKS) is increasingly being used in the management of brain metastases. The goal of this study is to determine the impact of ER status in patients receiving GKS for breast cancer metastases to brain. METHODS: A database of consecutive breast cancer patients receiving GKS at our institution from January 2000 to March 2012 was reviewed for hormone receptor status, dates of initial brain metastasis and GKS, presence of neurologic symptoms, and recurrence of GKS-treated lesions. The main cohort was subdivided by receptor status at initial tissue diagnosis. Progression or loss of local control of the treated lesions was defined as radiographic evidence of growth (greater than 20% increase in the sum of the longest diameters) or treated lesions requiring additional treatment until death or last follow-up. Analysis for neurological symptom improvement was performed for patients with available follow-up information, with at least 1 month follow–up. Comparisons were made between subgroups using Kaplan-Meier method, Chi-square analysis and univariate comparisons with log-rank test. Significance was set at p &amp;lt; 0.05. RESULTS: A total of 93 breast cancer patients received GKS, and receptor status was available in 83 patients. Forty-six (45.7%) percent of patients were ER+. The median follow-up for all patients was 85.5 months (range 2.5 to 307.6). For all patients, the median number of brain metastases was 2.0 and median age at diagnosis was 54 years. According to ER status, there were no differences in patient age at diagnosis, age at GKS, or number of brain metastasis, although the time to development of brain metastasis (median 92.2 vs 34.0 months, p = 0.02) was longer in the ER+ cohort. The median GKS dose was 18 Gy. Fifty one percent of ER+ patients had GKS alone versus 54% of ER− patients (p = 0.26). There was no difference in survival from GKS according to ER status, with survival for ER+ and ER− patients of 21.3 and 16.8 months, respectively (p = 0.39). However, ER+ patients exhibited longer progression-free survival of treated metastases with 19.1 versus 7.5 months (p = 0.02). In addition, for all patients who attained local control, 10 of 22 ER+ patients had an improvement in neurologic symptoms versus 4 of 17 ER− patients (p = 0.02). DISCUSSION: While ER positivity conveys a favorable prognosis at the time of diagnosis, survival after intensive treatment of brain metastases appears similar to ER− patients. This occurs independently of ER status, even though brain relapse was significantly more common in ER− patients, suggesting efforts to further improve extracranial systemic control may potentially enhance survival. Both local and neurologic symptom control were poorer for ER− patients. Whether alternative approaches, such as increasing GKS dose, surgical resection, and/or routine inclusion of WBRT, can improve outcomes for ER− patients with brain metastases may warrant future investigation. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-12-02.

The Effect of Tumor Subtype on the Time From Primary Diagnosis to Development of Brain Metastases and Survival in Women With Breast Cancer

Our group has previously published the Diagnosis-Specific Graded Prognostic Assessment (GPA) showing the prognostic factors associated with survival in patients with brain metastases (BM). The purpose of this study is to investigate the relationship of breast cancer subtype to the time interval from primary diagnosis (PD) to development of BM (TPDBM), number of BM at initial BM presentation and survival. We analyzed our previously described multi-institutional retrospective database of 865 breast cancer patients treated for newly-diagnosed BM from 1993 to 2010. Several factors found to be associated with survival were incorporated into the Breast-GPA, including tumor subtype. The GPA database was further analyzed to determine if the subtype correlated with the TPDBM, number of BM, and survival from PD. After exclusions for incomplete data, 383 patients remained eligible for analysis. The subtypes were approximated as follows: Luminal B: triple positive; HER2: HER2 positive/ER/PR negative; Luminal A; ER/PR positive/HER2 negative; Basal: triple negative. Patients with Basal (90), HER2 (119), Luminal B (98) and Luminal A (76) tumor subtypes had a median TPDBM of 27.5, 35.8, 47.4 and 54.4 months (p < 0.01), median survival from PD of 39.6, 66.4, 90.3 and 72.7 months (p < 0.01) and median survival from BM of 7.3, 17.9, 22.9 and 10.0 months (p < 0.01), respectively. Tumor subtype is an important prognostic factor for survival in patients with breast cancer and BM. Although TPDBM is not an independent prognostic factor for survival (and thus not part of the Breast-GPA), the TPDBM does correlate with tumor subtype but does not correlate with the number of BM. Patients with Basal and HER2 tumor subtypes have short TPDBM. Prospective studies are needed to determine if screening brain MRIs are indicated in patients with Basal or HER2 subtypes.

Brain metastases in patients with urothelial carcinoma.

e15009 Background: Muscle invasive urothelial cancers are infrequent. Patients (pts) with metastatic disease have poor prognosis. Brain metastases (BM) are rare. The aim of this retrospective study is to analyse the characteristics, the treatment and the evolution of patients with BM treated in a single centre. Methods: Thirty pts with BM were identified among the 1591 pts with urothelial carcinoma seen at the Centre Léon Bérard, between 1994 and 2011. The study population was described, overall survival (OS) from diagnosis of BM was estimated by Kaplan-Meier method and prognostic factors were explored using a Cox model. Results: Twenty seven pts in our series were male. Median age at initial diagnosis was 60 years (range: 33.9-78.9 years). Twenty two pts had primary bladder tumours and 8 upper urinary tract tumours. Twenty four pts underwent surgery for their primary lesion, 2 received chemoradiotherapy and 4 did not receive any radical local treatment. Six pts had metastatic disease at initial presentation: 3 were operated on. Median delay between initial diagnosis and BM was 16.6 months (range: 0-56.4 months), 3 patients had BM at initial presentation. Median time between first metastases and BM was 10 months (range=0-52 months). Eleven patients developed BM as one of the first sites of metastases. BM were symptomatic in 28 pts: specific neurological symptoms (n=25), headaches (n=6), epilepsy (n=2). For the 2 other pts, they were discovered on a systematic brain MRI. Eighteen pts had cerebral metastases only, 5 pts had cerebellar metastases only, 6 had both; the last patient had cerebral, cerebellar and meningeal involvement. Half of the pts had only 1 brain lesion. Five pts were operated on: 4 received postoperative radiotherapy; 19 patients were given radiotherapy alone and 6 did not get any local therapy. In this series, median OS from diagnosis of BM was 3.4 months (IC95% [2.2-10.3]). Only the administration of chemotherapy after the diagnosis of BM was significantly associated with OS; probably because only fit enough patients were offered treatment. Conclusions: Prognosis of patients with urothelial carcinoma and BM is poor; however some patients have long survivals. Treatment is not codified as there is little data in the literature.

Outcomes in 12 gynecologic cancer patients with brain metastasis: a single center’s experience

To present 12 gynecologic cancer cases with brain metastasis and a discussion of the relevant literature. Gynecologic malignancy is the second most common cancer in elderly women, following breast cancer. These cancers usually spread locally at first, and common distant metastatic sites are the lungs, liver, spleen, and distant lymph nodes. The brain is not a usual site of metastatic involvement. Materials and methods: The study included 12 cases with various gynecologic malignancies that were retrospectively analyzed. Therapeutic modalities, survival, and time between initial surgery and brain metastasis were recorded. Results: The mean survival was 41.4 months in 6 patients with ovarian cancer versus 27.7 months in those with other gynecological cancers. At the time of brain metastasis, the CA-125 level was elevated in all of the patients, except one that had cervical cancer. The mean CA-125 level was 202 IU mL-1. There were no differences in the mean overall survival between the patients that underwent surgical resection and those that received medical treatment. Conclusion: Brain metastasis can occur in all gynecologic cancers and has a poor prognosis, despite multimodal treatment.

P1-10-02: Burden of Brain Metastases in HER2−Positive Breast Cancer: Healthcare Use and Costs from a French Observational Retrospective Multicenter Study.

Abstract Background HER2+ status is associated with poor prognosis and a high incidence of brain metastases (BM) in breast cancer (BC). Addition of HER2−targeted therapies to conventional chemotherapy has significantly improved survival in HER2+ patients (pts). Management of BM implies a multidisciplinary therapeutic approach involving medical oncology, radiation oncology and neurosurgery teams. Nevertheless available data evaluating health resources use and associated costs are limited. Our objective was to describe treatment patterns and healthcare costs associated with HER2+ BMBC patients. Patients and methods An observational retrospective study was conducted on 207 HER2+ BC pts, newly diagnosed with BM as first site of relapse or as secondary metastases between January 2006 and December 2008. Pts were recruited in 10 hospitals, all funded by a prospective payment system based on Diagnosis Related Groups (DRG). Individual data concerning initial diagnosis, distant and BM relapses, treatments, complications and hospitalization stays were collected during a 2 year — follow-up. DRGs 2007 official tariffs (per-case payment basis) and 2007 expensive innovative drugs tariffs (drugs paid to hospitals by Health Insurance in addition to per-case payments) were used to estimate direct medical costs from the Health Insurance perspective. Survival was estimated using Kaplan Meier method. In the presence of cost-censored data, a partitioned estimator was used to adjust censoring costs (Bang and Tsiatis, Biometrics, 2002). Results 91.8% (190/207) of BMBC pts received radiation therapy, 84.5% (175/207) received chemotherapy including HER2 targeted treatments and 12.6% (26/207) were treated by neurosurgery. 72.5% (150/207) of pts were hospitalized at least once during the follow-up period. Pts had on average 2.90 hospital stays (range 1–8). The median duration of stay was 9 days (1-221). Complications leading to re-hospitalization were recorded in 45.9% (95/207) of pts. The median overall survival from the diagnosis of BM was 13 m. Hospital healthcare costs were concentrated on the 6 first months following BM diagnosis. Mean cost of BMBC management was 18,480€/patient within the 6 first months and decreased to 16,306€ from 7–12 months, 15,844€ from 13–18 months, and 15,225€ from 19–24 months. The proportion of costs attributed to inpatient hospitalizations stay (treatments and complications) was similar to the one attributed to drugs whatever the period of follow-up. Pts with BM as first site of relapse consumed more healthcare resources compared to pts with secondary BM (38,813€/pt vs 32,253€/pt after one year of follow-up, respectively). Conclusions Healthcare resources spending is mainly concentrated at the beginning of metastatic disease management, especially for patients with BM as first site of relapse. These results illustrate the use of expensive treatments in the first months following BM diagnosis. Individual data derived from this observational study allowed us to gather more specifically treatment patterns for HER2+ BMBC in order to estimate the costs more accurately. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-10-02.

HER2-neu status as a predictor of survival in patients with brain metastases from primary breast adenocarcinoma

1016 Background: Recent data suggests that Her2-neu positivity predicts for development of brain metastases in patients with breast cancer. However, there now exists a targeted agent, trastuzumab, that provides excellent systemic control of Her2-positive (Her2 +) disease. We therefore explore the course of this disease as a function of Her2 status in patients with primary breast cancer who have developed brain metastases. Method: We retrospectively analyzed data from 50 consecutive patients with primary breast cancer who subsequently developed brain metastases. Factors evaluated included Her2-neu, ER/PR, T stage, nodal stage, use of whole brain radiotherapy (WBRT) as initial management of CNS disease, initial number of metastases, hormonal therapy, use of trastuzumab, and Karnofsky Performance Status (KPS). Overall survival (OS) was modeled using Cox proportional hazard. Kaplan-Meier analysis was used for significant predictors. Results: Median age was 49 years (28–78 y). Fifty-four percent of patients were Her2 +, whereas only 15% were ER +. All but one Her2 + patient received trastuzumab. Seventy-two percent were node positive, and only 5 patients were metastatic at time of diagnosis. T stage was as follows: T1 = 24%, T2 = 36%, T3 = 8%, and T4 = 16%. Adjuvant chemotherapy was administered to 90% of the sample, and 94% underwent radiation to the primary site. Sixty-six percent had &lt;= 3 initial brain metastases, and 38% underwent WBRT as part of their initial CNS management. Median followup was 55 weeks. A Cox multivariate model of OS yielded two independent predictors. Her2 positivity (p = 0.007) and &lt;= 3 initial brain metastases (p = 0.003) were associated independently with OS from time of initial diagnosis of CNS disease. Median survival and actuarial one year survival for Her2 + patients were 65 weeks and 87%, respectively, versus 33 weeks and 44% for Her2 negative patients (Mantel Cox p = 0.025). Conclusions: Although Her2 + patients appear to have a greater risk of developing brain metastases, overall survival from time of initial diagnosis of brain metastasis appears to be better in this cohort. This may be a function of the improved extracranial control provided by trastuzumab in patients with Her2+ disease. No significant financial relationships to disclose.

Outcome Variation among “Radioresistant” Brain Metastases Treated with Stereotactic Radiosurgery

To determine the influence of histopathological diagnosis on the outcome of "radioresistant" brain metastases treated with stereotactic radiosurgery (SRS). Patients (n = 189) with "radioresistant" brain metastases (n = 264) were consecutively treated with SRS between August 1991 and July 2002. The primary site of brain metastases was melanoma (n = 103), renal cell carcinoma (n = 77), and sarcoma (n = 9). The median age of the patients was 52 years, and the median Karnofsky Performance Scale score was 80. Initial brain metastasis presentation was single in 112 patients (59%). The median SRS dose was 18 Gy (range, 10-24 Gy). The median tumor volume was 1.6 cm3 (range, 0.06-27.5 cm3). The median follow-up of all patients was 7.4 months (range, 0.16-52 mo). The actuarial freedom from progression after 1 year was 64% for renal cell carcinoma patients, 47% for melanoma patients, and 0% for sarcoma patients (P < 0.001). The median survival time for all patients from time of SRS was 7.5 months. The rate of 1-year survival was 40% for renal cell carcinoma patients, 25% for melanoma patients, and 22% for sarcoma patients (P = 0.0354). The incidence of neurological death was lower among patients diagnosed with renal cell carcinoma (31%) than among patients with melanoma (66%) or sarcoma (60%) (P = 0.001). Survival after SRS is significantly worse for patients with melanoma and sarcoma brain metastases compared with patients with renal cell carcinoma. Our data show that progressive brain metastases seem to cause most of the cancer-related deaths among patients with SRS-treated melanoma and sarcoma brain metastases. Future investigations using chemotherapy or novel agents to enhance the effectiveness of SRS to melanoma and sarcoma brain metastases seem warranted.

Comparison of clinical neurological function and CT response during chemotherapy for initial brain metastasis from small cell lung cancer: Sorensen PS, Kristjansen PEG, Wagner A, Hansen HH. Department of Neurology, Rigshospitalet, DK-2100 Copenhagen. Acta Neurol Scand 1994;89:372–377

Comparison of clinical neurological function and CT response during chemotherapy for initial brain metastasis from small cell lung cancer: Sorensen PS, Kristjansen PEG, Wagner A, Hansen HH. Department of Neurology, Rigshospitalet, DK-2100 Copenhagen. Acta Neurol Scand 1994;89:372–377

Prospective evaluation of the effect on initial brain metastases from small cell lung cancer of platinum-etoposide based induction chemotherapy followed by an alternating multidrug regimen

During the 1980s reports describing the effect of systemic chemotherapy on brain metastases from chemosensitive tumours emerged, including a few retrospective reports on small cell lung cancer (SCLC) patients. Previously untreated SCLC patients with no other malignancy, but in some cases with mixed histological subtype, who had symptomatic brain metastases verified by contrast enhanced CT-scan, were treated with a multidrug combination chemotherapy regimen and no cranial irradiation. Radiotherapy was optional at cranial relapse or progression at the discretion of the physician in charge. The intracranial effect was evaluated by 4-weekly CT-scan and neurological examination, according to a standardized scoring system. Intracranial response, duration of response, neurological score, terminal CNS status, and survival. 21 patients were included, corresponding to 8.6% of consecutive SCLC patients at our institution. 8 patients died before follow-up leaving 13 evaluable for response. In the former group, all patients had WHO performance status of 3-4 compared to 6/13 in the latter group. Of the 13 evaluable patients, 1 had early progression in the CNS and 1 had no change. 11 had CT-scan verified response, with a median duration of 135 days. Most patients, including all complete responders, had improvement in their neurological score. 6 out of 11 responders died without active CNS disease. The crude median survival was 111 days, whereas the median survival (early deaths excluded) was 197 days. Systemic combination chemotherapy was effective for palliation of initial brain involvement in the majority of patients in a small consecutive series. The role of consolidating cranial irradiation in responders should be assessed by a randomized trial.

Superior Vena Cava Syndrome in Small-cell Lung Cancer

The aim of this study was to analyze the features of the superior vena cava syndrome (SVCS) as initial characteristics in small-cell lung cancer: incidence, dissemination of disease, diagnostic procedures, efficacy and toxic effects of chemotherapy, and median survival in patients with SVCS. In a prospective series of 724 patients with biopsy-proved small-cell lung cancer seen during a 6-year period, we reviewed data from patients who also had SVCS. The incidence of SVCS was 87 of 724 at the time of diagnosis. Initial emergency radiation therapy was not used in these patients. Diagnostic procedures in these patients were not associated with mortality. Rapid initiation of intensive chemotherapy, often with heparin therapy, resulted in complete or partial responses in 81% and no response in 12%; data were not evaluable in 7%. Two of these 87 patients died of aplasia within 4 weeks of chemotherapy. Median survival was not significantly different in the patients with SVCS (median, 42 weeks) and without SVCS (median, 40 weeks). A significant increase in initial brain metastases at the time of diagnosis was observed in patients with SVCS (22% vs 11%). Intensive chemotherapy is the first line of therapy in small-cell lung cancer. Histologic diagnostic procedures must be performed in patients with SVCS to adapt the treatment to the underlying cause. Initial emergency radiotherapy, before diagnosis or chemotherapy, does not seem to be useful in these patients. Computed tomography of the brain should be performed routinely in patients with SVCS, and prophylactic brain irradiation could be helpful in such patients. Apparently SVCS is not a poor prognostic factor in treated small-cell lung cancer.