Brain Metastases in Patients with Cancer of Unknown Primary

Between January 1985 and December 2000, 916 patients with brain metastases were treated with whole brain radiation therapy (WBRT) at the Department of Radiotherapy, University Hospital Freiburg. In 47 patients, a primary tumor could not be identified (cancer of unknown primary (CUP)). Sixteen patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 15 patients, biopsy alone in 12 patients. WBRT was applied with daily fractions of 2 or 3Gy to a total dose of 50 or 30Gy, respectively. According to the recursive partitioning analysis (RPA) classes of the Radiation Therapy Oncology Group for patients with brain metastases none of the patients met the criteria for Class I, 23 for Class II, and 24 for Class III.The median overall survival (OS) for all patients with brain metastases (n = 916) was 3.4 and 4.8 months for patients with CUP (p = 0.45). In patients with CUP (n = 47) the median OS for patients with a single brain metastasis was 7.3 versus 3.9 months for patients with multiple brain metastases (p = 0.05). Median OS for patients with a Karnofsky performance status (KPS) 70 was 6.3 months versus 3.2 months for KPS <70 (p = 0.01).At multivariate analysis performance status and resection status could be identified as independent prognostic factors for the OS.     

Impact of anti-HER2 therapy on overall survival in HER2-overexpressing breast cancer patients with brain metastases

Background:

Trastuzumab-based therapy after diagnosis of brain metastases (BM) may improve survival due to prolonged systemic disease control. We investigated whether lapatinib may yield additional survival benefit.

Methods:

Eighty patients with BM from HER2-positive breast cancer were identified. Karnofsky Performance Score (KPS) of at least 70 was required. We included a control group of 37 patients treated before 2003, when continuation of trastuzumab after diagnosis of BM was not yet recommended. Remainders received either trastuzumab or lapatinib and trastuzumab (either concomitantly or sequentially) with or without chemotherapy.

Results:

Median overall survival (OS) in patients receiving trastuzumab after diagnosis of BM was 13 months; corresponding numbers were 9 months in patients treated with chemotherapy, and 3 months with radiotherapy alone. Median OS was not reached in the lapatinib group. Addition of lapatinib prolonged OS over trastuzumab alone (P=0.002). After correction for potential confounders, lapatinib therapy remained an independent positive predictor for survival (HR 0.279; P=0.012).

Interpretation:

This retrospective single-centre study suggests that the introduction of lapatinib improved survival in patients with BM from HER2-positive breast cancer. Patients with KPS ⩾70 may benefit when treated with lapatinib in addition to trastuzumab after completion of local therapy.     

Intensified local treatment and systemic therapy significantly increase survival in patients with brain metastases from advanced breast cancer – A retrospective analysis

BACKGROUND: Brain metastases have evolved from a rare to a frequently encountered event in advanced breast cancer due to advances in palliative systemic treatment. PATIENTS AND METHODS: All Patients treated at our centre from 1994 to 2004 with WBRT for brain metastases from breast cancer were included. We performed a multivariate analysis (Cox regression) to explore which factors are able to influence significantly cerebral time to progression (TTP) and overall survival (metastatic sites [visceral versus non-visceral], Karnofsky performance score [KPS], age, intensified local treatment [boost irradiation, neuro-surgical resection] further systemic treatment). RESULTS: Overall 174 patients, median age 51 years, range 27-76 years, were included. Median TTP was 3 months (m), range 1-33+ m. Median overall survival was 7 m, range 1-44 m. Factors significantly influencing TTP were KPS (p = 0.002), intensified local treatment (p < 0.001), and palliative systemic treatment (p = 0.001). Factors significantly influencing survival were intensified local treatment (p = 0.004), metastatic sites (p = 0.008), KPS (p = 0.006), and palliative systemic treatment (p < 0.001). CONCLUSION: As shown by the significant influence of metastatic sites, some patients die from their advanced systemic tumour situation before they would die from cerebral progression. In other individuals however, intensified local treatment and systemic treatment appear to influence cerebral time to progression and overall survival.     

Concurrent whole-brain radiotherapy with trastuzumab for treatment of brain metastases in breast cancer patients: questions and answers

PurposeWe retrospectively assessed the use of trastuzumab concurrently with whole-brain radiotherapy (WBRT) for brain metastases.Patients and methodsFrom April 2001 to April 2007, 31 patients with brain metastases from HER2-positive breast cancer were referred for WBRT with concurrent trastuzumab. In most cases, concurrent WBRT delivered 30 Gy in 10 daily fractions. In six patients, other fractionations were chosen because of either poor performance status or patients’ convenience.ResultsAt time of brain progression, median age was 55 years (range: 38 to 73 years) and all patients had a performance status of 0 to 2. Median time to brain progression was 10.5 months. Following WBRT, radiological responses were observed in 23 patients (74.2%), including six patients (19.4%) with complete radiological responses and 17 patients (54.8%) with partial radiological response. Clinical responses were observed in 27 patients (87.1%). Median survival from the start of WBRT was 18 months (range: two to 65 months). No grade 2 or more acute toxicity was observed.ConclusionOur results suggest that trastuzumab concurrently with WBRT may have a potential clinical impact with low toxicity. Although promising, these preliminary data warrant further validation of trastuzumab as radio sensitizer for WBRT in brain metastases from breast cancer in the setting of a clinical trial. Larger prospective studies are needed to confirm these results.     

Survival outcomes after whole brain radiotherapy for brain metastases in older adults with newly diagnosed metastatic small cell carcinoma: A national cancer database (NCDB) analysis

BackgroundSmall cell lung cancer (SCLC) is an aggressive malignancy with a tendency to affect older adults and also metastasize to the brain. Older adults tolerate whole brain radiotherapy (WBRT) poorly with marginal survival benefit. We utilized the national cancer database (NCDB) to evaluate the survival outcomes following WBRT in older adults with SCLC and brain metastases.MethodsWe identified 1615 patients ≥75 years old diagnosed with SCLC and brain metastases. Patients were categorized by type of therapy: chemotherapy + WBRT (n = 576), chemotherapy alone (n = 238), WBRT alone (n = 360) and no chemotherapy or WBRT (n = 441). Clinical and demographic characteristics were reported for each treatment cohort with a subsequent multivariable regression analysis for survival.ResultsMedian patient age was 79 years. WBRT median dose was 30 Gy. At time of analysis, 1530 of the cohort had died, yielding a median OS of 2.9 months and 6 month survival of 31% for patients that received chemotherapy. For patients treated without chemotherapy, median OS with WBRT was 1.9 months compared to 1.2 months without (p < .0001). For patients receiving chemotherapy with, and without WBRT, median OS was 5.6 months and 6.4 months, respectively (p = .43). Multivariable cox regression revealed age > 80, extracranial disease, male sex, and rural location as predictors of increased risk of death.ConclusionIn older adult patients with SCLC brain metastasis, WBRT was associated with a modest increase in survival in patients not fit for chemotherapy, and there was no association with increased survival over chemotherapy alone.     

EGFR,pMAPK, pAkt and PTEN status by immunohistochemistry: correlation with clinical outcome in HER2-positive metastatic breast cancer patients treated with trastuzumab

BackgroundIn an attempt to identify markers of resistance to trastuzumab, we evaluated both the profiling of human epidermal growth factor receptor 2 (HER2)-positive tumor cells measuring the relative levels of EGFR, pMAPK, pAkt and PTEN and their correlations with clinical outcome in HER2-positive metastatic breast cancer patients treated with trastuzumab.Patients and methodsTumor tissues for this retrospective analysis were available from 45 out of 76 patients with metastatic breast cancer treated from April 1999 to March 2006 with trastuzumab-based therapy at our Institution. Evaluations of EGFR, pMAPK, pAkt and PTEN status by immunohistochemistry (IHC) were carried out on all 45 tissue samples and their correlations with response to trastuzumab, incidence of central nervous system (CNS) metastases, time to progression (TTP), overall survival from diagnosis of breast cancer (OS1), from diagnosis of metastatic disease (OS2) and from the start of trastuzumab (OS3) were analyzed.ResultsWe observed that TTP (P = 0.001) and median OS2 and OS3 were significantly longer in patients responsive to trastuzumab-based regimen compared with nonresponsive patients. EGFR, pMAPK, pAkt and PTEN status by IHC were not significantly associated with response to trastuzumab, TTP, overall survival (OS1, OS2, OS3) and CNS metastases incidence. A trend for shorter OS3 was observed for pMAPK-positive patients compared with pMAPK-negative patients (22.8 versus 31.2 months; P = 0.076). Median OS1 resulted shorter in 22 pAkt-positive patients (69.8 months) compared with 23 pAkt-negative patients (108.2 months); P = 0.091. It is likely that high expression of pMAPK (pMAPK-positive status) or pAkt (pAkt-positive status) could identify a subgroup of HER2-positive tumors with high activity of proliferation and survival pathways and with resistance to trastuzumab.ConclusionsIn HER2-positive metastatic breast cancers, EGFR, pMAPK, pAkt and PTEN status evaluated by IHC was not significantly associated with response to trastuzumab, TTP, OS and CNS metastases incidence. However, HER2 status determined by IHC and/or FISH assays may not be sufficient to predict response to trastuzumab-based therapy.     

First‐line epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor alone or with whole‐brain radiotherapy for brain metastases in patients with EGFR‐mutated lung adenocarcinoma

We proposed to compare the outcomes of first‐line epidermal growth factor receptor–tyrosine kinase inhibitor (EGFR‐TKI) alone with EGFR‐TKI plus whole‐brain radiotherapy (WBRT) for the treatment of brain metastases (BM) in patients with EGFR‐mutated lung adenocarcinoma. A total of 1665 patients were screened from 2008 to 2014, and 132 were enrolled in our study. Among the 132 patients, 72 (54.5%) harbored a deletion in exon 19, 97 (73.5%) showed multiple intracranial lesions, and 67 (50.8%) had asymptomatic BM. Seventy‐nine patients (59.8%) were treated with EGFR‐TKI alone, 53 with concomitant WBRT. The intracranial objective response rate was significantly higher in the EGFR‐TKI plus WBRT treatment group (67.9%) compared with the EGFR‐TKI alone group (39.2%) (P = 0.001). After a median follow‐up of 36.2 months, 62.1% of patients were still alive. The median intracranial TTP was 24.7 months (95% CI, 19.5–29.9) in patients who received WBRT, which was significantly longer than in those who received EGFR‐TKI alone, with the median intracranial TTP of 18.2 months (95% CI, 12.5–23.9) (P = 0.004). There was no significant difference in overall survival between WBRT and EGFR‐TKI alone groups, (median, 48.0 vs 41.1 months; P = 0.740). The overall survival is significantly prolonged in patients who had an intracranial TTP exceeding 22 months compared to those who developed intracranial progression <22 months after treatment, (median, 58.0 vs 28.0 months; P = 0.001). For EGFR‐mutated lung adenocarcinoma patients with BM, treatment with concomitant WBRT achieved a higher response rate of BM and significant improvement in intracranial progression‐free survival compared with EGFR‐TKI alone.     

非小细胞肺癌脑转移患者全脑放疗不同剂量预后分析

目的:分析非小细胞肺癌(NSCLC)脑转移患者不同全脑放疗(WBRT)剂量的预后及影响因素。方法:回顾性分析2013—2015年间于河北医科大学第四医院行WBRT的244例NSCLC脑转移患者。按照不同WBRT剂量(EQD 2Gy)分为30~39 Gy组104例、≥40 Gy组140例。比较两组患者颅内无进...     

Multifocal glioblastoma multiforme: prognostic factors and patterns of progression

PURPOSE: To assess the progression patterns in patients with multifocal glioblastoma multiforme who had undergone whole brain radiotherapy (WBRT), the historical standard, versus three-dimensional conformal radiotherapy, and to identify predictive treatment and pretreatment factors. METHODS AND MATERIALS: The records of 50 patients with multifocal glioblastoma multiforme treated with RT were reviewed. Univariate analyses were performed using survival methods and the Cox proportional hazards regression method. Multivariate analyses were performed using the Cox proportional hazards regression method. RESULTS: The mean age was 61 years, and 71% had a Karnofsky performance status (KPS) score of > or =70. Of the 50 patients, 32% underwent WBRT and 68%, three-dimensional conformal RT. Progression was local in all evaluable patients, as determined by imaging in 38 patients and early neurologic progression in 12. The median time to progression (TTP) was 3.1 months, and the median survival time (MST) was 8.1 months. The significant independent predictors of TTP on multivariate analysis were a KPS score <70 (p = 0.001), the extent of surgery (p = 0.040), a radiation dose <60 Gy (p = 0.027), and the lack of chemotherapy (p = 0.001). The significant independent predictors of a reduced MST were a KPS score <70 (p = 0.022) and the absence of salvage surgery (p = 0.011) and salvage chemotherapy (p = 0.003). CONCLUSION: Local progression was observed in all patients. On multivariate analysis, no significant difference was found in the TTP or MST between three-dimensional conformal radiotherapy and WBRT. The KPS was a consistent independent predictor of both TTP and MST. On the basis of the progression pattern, we do not recommend WBRT as a mandatory component of the treatment of multifocal glioblastoma multiforme.     

全脑放疗时间对EGFR突变非小细胞肺癌脑转移患者生存的影响

背景与目的全脑放疗（whole brain radiotherapy, WBRT）在表皮生长因子受体（epidermal growth factor receptor,EGFR）突变的非小细胞肺癌（non-small cell lung cancer, NSCLC）脑转移患者治疗中何时应用尚无高级别的循证医学证据。本研究旨在探讨WBRT的参与时间对携有EGFR突变的NSCLC脑转移患者生存的影响。方法2009年8月-2015年5月在我院确诊的EGFR突变伴脑转移的晚期NSCLC共78例患者,均接受WBRT及EGFR酪氨酸激酶抑制剂（EGFR tyrosine kinase inhibitors, EGFR-TKIs）治疗的48例初治患者进入临床分析,采用Cox比例风险模型分析患者颅内无进展生存期（progression-free survival, PFS）及总生存期（overall survival, OS）的影响因素。结果全组患者颅内客观缓解率（objective response rate, ORR）为81.3%,颅内疾病控制率（disease control rate, DCR）为93.8%,中位颅内PFS为10个月,中位OS为18个月。颅内PFS的多因素分析显示,美国东部肿瘤协作组评分（Eastern Cooperative Oncology Group performance status, ECOG PS）0分-1分（HR=30.436,95%CI：4.721-196.211,P<0.001）及早期WBRT患者（HR=3.663,95%CI：1.657-8.098,P=0.001）的颅内PFS更佳。OS的多因素分析显示,ECOG PS 0分-1分（HR=57.607,95%CI：6.135-540.953,P<0.001）、早期WBRT（HR=2.757,95%CI：1.140-6.669,P=0.024）及立体定向放射外科（stereotaxic radio surgery, SRS）的应用（HR=5.964,95%CI：1.895-18.767,P=0.002）是患者OS的独立预后因素。结论早期WBRT联合TKIs治疗可改善EGFR突变的NSCLC脑转移患者的预后,尚有待大样本的前瞻性临床试验验证。     

Biological subtypes and survival outcomes in breast cancer patients with brain metastases (study of the anatolian society of medical oncology)

Background: The aim of this study is to determine the relationship between the survival outcomes and biological subtype in breast cancer patients with brain metastases. Methods: We retrospectively evaluated clinical data from 422 breast cancer patients with brain metastases between 2001 and 2011 from referral centers in Turkey. The study population was divided into four biological subtypes according to their hormone receptor status and HER2 expression. Results: Systemic treatment prolonged median overall survival (OS) after brain metastases in the entire group (14 vs. 3.2 months, p < 0.001). It also prolonged median OS after brain metastases in the triple negative (7.5 vs. 1.6 months, p = 0.010) and luminal A (14.3 vs. 7.1 months, p = 0.003) subgroups. The median OS for untreated patients, chemotherapy and/or hormonal therapy receiving patients, and chemotherapy and/or hormonal therapy plus targeted therapy receivers was 2, 5.8, and 17.7 months, respectively (p < 0.001), in the HER2-overexpressing subgroup. In the luminal B subgroup, it was 3.7, 5.3, and 15.4 months, respectively (p = 0.003). Conclusions: The use of systemic therapy improves OS after brain metastases in all biological subgroups. Targeted therapies also improve OS after brain metastases in HER2-positive patients. The combined use of targeted therapies and lapatinib are superior to single use and trastuzumab, respectively, in these patients.     

Whole-brain radiotherapy with and without concurrent erlotinib in NSCLC with brain metastases: a multicenter,open-label,randomized, controlled phase III trial

BackgroundErlotinib combined with whole-brain radiotherapy (WBRT) demonstrated a favorable objective response rate in a phase II single-arm trial of non–small cell lung cancer (NSCLC) patients with brain metastases. We assessed whether concurrent erlotinib with WBRT is safe and benefits patients in a phase III, randomized trial.MethodsNSCLC patients with two or more brain metastases were enrolled and randomly assigned (1:1) to WBRT (n = 115) or WBRT combined with erlotinib arms (n = 109). The primary endpoint was intracranial progression-free survival (iPFS) and cognitive function (CF) was assessed by the Mini-Mental State Examination (MMSE).ResultsA total of 224 patients from 10 centers across China were randomized to treatments. Median follow-up was 11.2 months. Median iPFS for WBRT concurrent erlotinib was 11.2 months vs 9.2 months for WBRT-alone (P = .601). Median PFS and overall survival (OS) of combination group were 5.3 vs 4.0 months (P = .825) and 12.9 vs 10.0 months (P = .545), respectively, compared with WBRT-alone. In EGFR-mutant patients, iPFS (14.6 vs 12.8 months; P = .164), PFS (8.8 vs 6.4 months; P = .702), and OS (17.5 vs 16.9 months; P = .221) were not significantly improved in combination group over WBRT-alone. Moreover, there were no significant differences in patients experiencing MMSE score change between the treatments.ConclusionConcurrent erlotinib with WBRT didn’t improve iPFS and excessive CF detriment either in the intent-to-treat (ITT) population or in EGFR-mutant patients compared with WBRT-alone, suggesting that while safe for patients already taking the drug, there is no justification for adding concurrent EGFR-TKI with WBRT for the treatment of brain metastases. Trial registration: Clinical trials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT01887795","term_id":"NCT01887795"}}NCT01887795     

Two radiation regimens and prognostic factors for brain metastases in nonsmall cell lung cancer patients

BACKGROUND: Nonsmall cell lung cancer (NSCLC) patients with brain metastases usually receive whole-brain radiotherapy (WBRT). Most of these patients survive for only a few months. A short course of WBRT would be preferable to longer regimens if it could provide similar survival. This retrospective study of NSCLC patients compared longer treatment programs with short-course WBRT with 5 x 4 Gy given during 5 days. METHODS: Data from 404 NSCLC patients treated with WBRT for brain metastases were retrospectively analyzed. The 140 patients who received 5 x 4 Gy given in 5 days were compared for survival with 264 patients who received either 10 x 3 Gy given in 2 weeks or 20 x 2 Gy given in 4 weeks. Seven further potential prognostic factors were investigated for survival including age, sex, Karnofsky performance score (KPS), number of brain metastases, extracranial metastases, interval from tumor diagnosis to WBRT, and RPA (recursive partitioning analysis) class. RESULTS: The WBRT regimen was not associated with survival (P = .55). On multivariate analysis, age < 60 years (vs > or =60 years, P = .020), KPS > or =70 (vs KPS < 70, P < .001), interval from tumor diagnosis to WBRT > 12 months (vs < or =12 months, P = .007), no extracranial metastases (P < .001), and RPA class 1 (vs RPA class 2 vs RPA class 3, P = .007) were significantly associated with improved survival. CONCLUSIONS: Short-course WBRT with 5 x 4 Gy appeared preferable for most NSCLC patients, as it was associated with survival similar to longer WBRT programs, and the short course was less time consuming.     

Salvage stereotactic radiosurgery effectively treats recurrences from whole-brain radiation therapy

BACKGROUND.

The purpose of the current study was to examine overall survival (OS) and time to local failure (LF) in patients who received salvage stereotactic radiosurgery (SRS) for recurrent brain metastases (BM) after initial management that included whole‐brain radiation therapy (WBRT).

METHODS.

The records of 1789 BM patients from August 1989 to November 2004 were reviewed. Of these, 111 underwent WBRT as part of their initial management and SRS as salvage. Patients were stratified by Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis class, primary disease, dimension of the largest metastases and number of BM at initial diagnosis, and time to first brain recurrence after WBRT. Overall survival, survival after SRS, and time to local and distant failure were analyzed.

RESULTS.

The median OS from the initial diagnosis of BM was 17.7 months. Median survival after salvage SRS for the entire cohort was 9.9 months. Median survival after salvage SRS was 12.3 months in patients who had their first recurrence >6 months after WBRT versus 6.8 months for those who developed disease recurrence ≤6 months after (P = .0061). Primary tumor site did not appear to affect survival after SRS. Twenty‐eight patients (25%) developed local recurrence after their first SRS with a median time of 5.2 months. A dose <22 grays and lesion size >2 cm were found to be predictive of local failure.

CONCLUSIONS.

In this study, patients who recurred after WBRT and were treated with salvage SRS were found to have good local control and survival after SRS. WBRT provided good initial control, as 45% of these patients failed >6 months after WBRT. Those with a longer time to failure after WBRT had significantly longer survival after SRS. Cancer 2008. © 2008 American Cancer Society.     

不同EGFR突变肺腺癌脑转移患者WBRT分析

目的 探讨肺腺癌脑转移患者不同EGFR突变状态WBRT疗效差别。方法 回顾分析2010—2015年在本院诊治的89例肺腺癌脑转移患者,所有患者均行EGFR检测。脑转移一线6 MV X线外照射:WBRT30 Gy分10次或40 Gy分20次(≤3个脑转移灶IMRT同步加量40~45 Gy分10次或50~60 Gy分20次)。比较EGFR突变和野生型患者的有效率、IPFS、OS。Kaplan-Meier法计算IPFS、OS并Logrank检验和单因素分析,Cox模型多因素分析。结果 89例患者总有效率为62%,中位IPFS为7.0个月(95%CI为6.060~7.940),中位OS为12.0个月(95%CI为9.539~14.465)。单因素和多因素分析结果显示脑转移患者有效率与KPS评分、EGFR突变状态相关(P=0.009、0.035),KPS评分、EGFR突变状态是IPFS的影响因素(P=0.048、0.000),KPS评分、原发灶控制是OS的影响因素(P=0.000、0.031)。结论 肺腺癌脑转移患者WBRT后,EGFR突变较野生型有效率高,IPFS时间长,OS无差别。     

Retreatment with trastuzumab-based therapy after disease progression following lapatinib in HER2-positive metastatic breast cancer

BackgroundPreclinical data suggest that treatment with lapatinib reinduces sensitivity to trastuzumab in human epidermal growth factor receptor 2(HER2)-positive breast cancer cells.Patients and methodsBetween January 2007 and November 2010, 179 HER2-positive metastatic breast cancer patients were treated with lapatinib and capecitabine at nine Italian institutions. We evaluated the clinical outcome of 69 patients (38.5%) retreated with trastuzumab after lapatinib progression.ResultsVisceral metastases were identified in 51 (74%) and brain metastases in 16 patients (23%). All patients were pretreated with both trastuzumab- and lapatinib-based therapy. We observed with retreatment with trastuzumab-based therapy: 1 complete remission (2%), 18 partial remission (29%) and 10 stable disease ≥6 months (14%) and 47% of clinical benefit (CB). Median duration of response was 8.1 months [95% confidence interval (CI) 5.5–10.7]. No unexpected toxic effects occurred. At a median follow-up of 13 months, median progression-free survival was 4.9 months (95% CI 4.2–5.6) and overall survival (OS) 19.4 months (95% CI 14.0–25.0). Median OS was longer for patients experiencing CB (not reached versus 13.4 months for patients without CB, P = 0.002). Brain involvement was associated with lower median OS (17.3 versus 23.3 months for patients without brain disease; P = 0.021).ConclusionRetreatment with trastuzumab-based therapy showed CB in 47% of patients progressing during lapatinib-based therapy, leading to a prolonged OS.     

Time for reappraisal of extracranial treatment options?

BACKGROUND.

The optimal treatment of the primary tumor in patients with brain metastases (BM) from newly diagnosed nonsmall cell lung cancer (NSCLC) remains unclear. The authors aimed to identify patient groups with synchronous BM for whom radical treatment of the primary site may be appropriate.

METHODS.

The medical records of 167 patients treated at our center between November 2000 and June 2009 for newly diagnosed NSCLC and synchronous BM were reviewed. All patients underwent surgery/radiosurgery (n = 86) or whole‐brain radiotherapy (WBRT; n = 81) for BM. Univariate and multivariate analyses assessed prognostic factors significant for overall survival (OS).

RESULTS.

Median OS of patients undergoing surgery/radiosurgery for BM was 12.1 months. Those undergoing “radical” thoracic treatment (n = 24) had a longer median OS (28.4 months) than those undergoing chemotherapy (n = 74; 12.1 months) or supportive therapy (n = 69; 5.6 months, P < .01). Patients with stage I thoracic disease (n = 23) had a longer median OS (18.5 months) than those with stage III (n = 43; 9.4 months) or with intra/extra‐thoracic metastases other than BM (stage IV; n = 20; 2.7 months, P < .01). Median OS of WBRT patients was 3.7 months. One patient underwent radical thoracic treatment. Patients undergoing chemotherapy (n = 42) had a longer median OS (5.7 months) than patients undergoing supportive therapy only (n = 38; 1.6 months, P < .01). Performance status and age were also associated with OS.

CONCLUSIONS.

Radical thoracic treatments may be justified in selected patients <65‐years‐old, eligible to undergo surgery/radiosurgery for synchronous BM from NSCLC, even when stage III thoracic disease is present. Cancer 2011. © 2010 American Cancer Society     

Intracranial control and radiographic changes with adjuvant radiation therapy for resected brain metastases: whole brain radiotherapy versus stereotactic radiosurgery alone

The aim of this study was to compare outcomes of postoperative whole brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) alone in patients with resected brain metastases (BM). We reviewed records of patients who underwent surgical resection of BM followed by WBRT or SRS alone between 2003 and 2013. Local control (LC) of the treated resected cavity, distant brain control (DBC), leptomeningeal disease (LMD), overall survival (OS), and radiographic leukoencephalopathy rates were estimated by the Kaplan–Meier method. One-hundred thirty-two patients underwent surgical resection for 141 intracranial metastases: 36 (27 %) patients received adjuvant WBRT and 96 (73 %) received SRS alone to the resection cavity. One-year OS (56 vs. 55 %, p = 0.64) and LC (83 vs. 74 %, p = 0.31) were similar between patients receiving WBRT and SRS. After controlling for number of BM, WBRT was associated with higher 1-year DBC compared with SRS (70 vs. 48 %, p = 0.03); single metastasis and WBRT were the only significant predictors for reduced distant brain recurrence in multi-variate analysis. Freedom from LMD was higher with WBRT at 18 months (87 vs. 69 %, p = 0.045), while incidence of radiographic leukoencephalopathy was higher with WBRT at 12 months (47 vs. 7 %, p = 0.001). One-year freedom from WBRT in the SRS alone group was 86 %. Compared with WBRT for patients with resected BM, SRS alone demonstrated similar LC, higher rates of LMD and inferior DBC, after controlling for the number of BM. However, OS was similar between groups. The results of ongoing clinical trials are needed to confirm these findings.     

吉非替尼同步γ射线立体定向外科加全脑放疗治疗非小细胞肺癌脑转移瘤的临床研究

评价吉非替尼同步伽马射线立体定向外科加全脑放疗治疗非小细胞肺癌（NSCLC）脑转移瘤的作用和获益影响因素。方法:回顾性分析23例NSCLC脑转移瘤患者接受吉非替尼同步γ射线立体定向外科治疗加全脑放疗后的疗效、疾病进展时间、总生存时间、预后影响因素及不良反应。结果:颅内病灶的疗效为:CR 2例,PR 16例,SD 3例,PD 2例,有效率78.3%（18/23）,疾病控制率91.3%（21/23）。全身病变的总体疗效为:CR 0例,PR 5例,SD 12例,PD 6例,有效率21.7%（5/23）,疾病控制率73.9%（17/23）。中位疾病进展时间为8.3个月,中位生存时间为12.8个月。单因素分析显示:KPS评分、肿瘤累及体积、病理类型、RPA分级为疾病进展时间预测因素（P均<0.05）;而KPS评分、肿瘤累及体积、RPA分级则是生存时间预测因素（P均<0.05）。吉非替尼不良反应主要为Ⅰ~Ⅱ度皮疹和腹泻,患者均可耐受。结论:吉非替尼同步γ射线立体定向外科治疗加全脑放疗后的治疗NSCLC脑转移瘤,有效率和疾病控制率高,具有较长的中位疾病进展时间和生存时间,不良反应轻微,是一种很有价值的治疗方法。其中,KPS评分、肿瘤体积、病理类型（腺癌）、RPA分级是影响获益和生存的重要因素。      

全脑放疗对广泛期小细胞肺癌脑转移的生存影响

目的 探索现代诊疗条件下,全脑放疗（WBRT）能否延长小细胞肺癌（SCLC）脑转移患者的生存期。方法 回顾性分析天津医科大学肿瘤医院2010—2020年245例伴有脑转移的广泛期SCLC患者的病历资料,其中WBRT组168例（剂量30 Gy分10次）,无WBRT组77例。所有患者均接受了至少2个周期的化疗,化疗方案均为顺铂或卡铂联合依托泊苷,115例接受了胸部放疗。研究终点为脑转移后生存期（BM‐OS）,采用卡方检验对分类数据进行比较,采用稳健逆概率处理加权（sIPTW）方法对组间变量进行匹配,采用Kaplan‐Meier方法进行生存分析,log‐rank检验进行生存曲线比较。结果 全组患者中位BM‐OS为9.1个月。有无WBRT患者的中位BM‐OS分别为10.6、6.7个月（P=0.003）,应用sIPTW平衡两组影响因素后,两组的BM‐OS差异仍具有统计学意义（P=0.02）。其中,首诊广泛期伴脑转移患者118例,有无WBRT的中位BM‐OS分别为13.0、9.6个月（P=0.007）;广泛期疗中出现脑转移患者127例,有无WBRT的中位BM‐OS分别为8.0、4.1个月（P=0.003）。在50例单纯脑转移患者中,有无WBRT的中位BM‐OS为13.3、10.9个月（P=0.259）;在195例伴有颅外转移的患者中,有无WBRT的中位BM‐OS分别为9.5、5.9个月（P=0.009）。结论 广泛期小细胞肺癌脑转移患者行全脑放疗能够为患者带来生存获益。