CNS Failure Research Articles

Non-Small Cell Lung Cancer With Single Brain Metastasis at Initial Presentation: Patterns of Failure After Radiosurgery Without Whole Brain Radiation Therapy

To characterize the natural history of patients with a single brain metastasis at initial diagnosis of non-small cell lung cancer (NSCLC) and treated with radiosurgery (SRS) alone. An IRB-approved institutional registry of SRS cases treated from 1/1997-7/2012 was queried for patients with newly diagnosed NSCLC treated with SRS for a single brain metastasis. Patients receiving adjuvant whole brain radiation therapy were excluded. Extracranial lung cancer stage, symptomatic disease, Karnofsky performance status(KPS), timing and sites of first progression, SRS treatment parameters and use of local thoracic therapy (surgery or radiation therapy) were included in the analysis. Survival was analyzed by Kaplan-Meier analysis and log-rank tests, with multivariable modeling using proportional hazards. Of 2100 lung cancer cases receiving SRS, 52 met criteria for this analysis. Median age was 64 years, median KPS was 90, and histology was adenocarcinoma (38.5%), squamous (23%) and other (38.5%). 76% of pts received chemotherapy and 42% of patients received thoracic therapy (12% XRT, 32% surgery). Median brain metastasis size was 1.55 cm and median SRS dose was 24 Gy (range, 15-24 Gy). Median overall survival (OS), progression free survival (PFS) and CNS progression free survivals (CNS-PFS) were 13.7, 4.6 and 6.1 months, respectively. Twenty-five (48%) of patients experienced in brain failure (76% in brain, 12% SRS local failure, 12% both) and in 18 (35%) brain failure was the first site of failure. 52% of patients were salvaged by SRS as the first modality. Actuarial rates of CNS failure among surviving patients at 6, 12 and 18 months after SRS were 45, 55 and 71%, respectively. Outside of the brain, patients with asymptomatic chest-only or asymptomatic systemic disease at the time of radiosurgery had median OS of 20.2 and 14.1 months, respectively. Among patients with progressive/symptomatic thoracic or systemic disease, OS was significantly inferior: median 4.6 and 1.4 months, respectively (p < 0.0001). Improved median OS was seen with high KPS (90-100) OS 21.7 vs 3.0 months (p = 0.0008), and chemotherapy treatment 20.5 vs 5.7 months (p = 0.0168) but neither was significant in a multivariable model. Patients with a single brain metastasis from NSCLC at first presentation can have prolonged survival but brain failure after SRS alone is common and often the site of first failure. Patients with a single brain metastasis and symptomatic extracranial NSCLC at diagnosis have very poor survival after SRS, suggesting minimal benefit from this modality in this setting.

Recurrence patterns of advanced non-small cell lung cancer treated with gefitinib

Background Gefitinib is widely used in the treatment of advanced non-small cell lung cancer (NSCLC). However, only a small number of reports have described initial failure sites in patients treated with gefitinib. The aim of this study was to investigate survival, recurrence sites, and treatment after recurrence in these patients. Methods A retrospective review was conducted of all patients with stage III/IV NSCLC treated with gefitinib in Peking Union Medical College Hospital from October 2002 to September 2011. Patient characteristics, initial failure sites, associated clinical factors, and subsequent therapy were included in the analysis of prognostic factors. Results A total of 316 patients were identified The median progress free survival (PFS) and overall survival (OS) times were 238 days and 468 days, respectively. The median survival time after progression was 145 days. The sites of initial failure were lung (62.34%), bone (17.72%), central nerve system (CNS, 16.14%), liver (9.49%), and others (7.19%). Patients with single-site progression or multi-site progression were 81.01% and 18.99%, respectively. Progression-free survival time was associated with lung and bone failure. Additionally, the median survival time after progression was lower in patients with multi-site progression and liver progression. Other initial failure sites displayed no relationship with survival, including CNS failure. Subsequent therapy may affect survival after progression. In patients receiving continuous epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy, chemotherapy, radiotherapy, and re-treatment with EGFR-TKIs, survival time after progression was prolonged compared with the best supportive care. Conclusions Our data suggest that patients receiving gefitinib should be closely monitored regarding lung metastasis during follow-up. Liver metastases and multi-site progression were poor prognostic factors. After failure with gefitinib, patients may benefit from radiotherapy, chemotherapy, continuous EGFR-TKI therapy and re-treatment with EGFR-TKIs.

Survival among patients with 10 or more brain metastases treated with stereotactic radiosurgery

The goal of this study was to evaluate outcomes in patients with ≥ 10 CNS metastases treated with Gamma Knife stereotactic radiosurgery (GK-SRS). Patients with ≥ 10 brain metastases treated using GK-SRS during the period between 2004 and 2010 were identified. Overall survival and local and regional control as well as necrosis rates were determined. The influence of age, sex, histological type, extracranial metastases, whole-brain radiation therapy, and number of brain metastases was analyzed using the Kaplan-Meier method. Univariate (log-rank) analyses were performed, with a p value of < 0.05 considered significant. Fifty-three patients with ≥ 10 brain metastases were treated between 2004 and 2010. All had a Karnofsky Performance Status score of ≥ 70. Seventy-two percent had either non-small cell lung cancer (38%) or breast cancer (34%); melanoma, small cell lung cancer, renal cell carcinoma, and testicular, colon, and ovarian cancer contributed the remaining 28%. On average, 10.9 lesions were treated in a single session. Sixty-four percent of patients received prior whole-brain radiation therapy. The median survival was 6.5 months. One-year overall survival was 42% versus 14% when comparing breast cancer and other histological types, respectively (p = 0.074). Age, extracranial metastases, number of brain metastases, and previous CNS radiation therapy were not significant prognostic factors. Although the median time to local failure was not reached, the median time to regional failure was 3 months. Female sex was associated with longer time to regional failure (p = 0.004), as was breast cancer histological type (p = 0.089). No patient experienced symptomatic necrosis. Patients with ≥ 10 brain metastases who received prior CNS radiation can safely undergo repeat treatment with GK-SRS. With median survival exceeding 6 months, aggressive local treatment remains an option; however, rapid CNS failure is to be expected. Although numbers are limited, patients with breast cancer represent one group of individuals who would benefit most, with prolonged survival and extended time to CNS recurrence.

Survival of Adult Rhabdomyosarcoma Patients Treated on Multimodality Protocols

Survival of Adult Rhabdomyosarcoma Patients Treated on Multimodality Protocols

Myelination disorders in the mechanism of hypogravity motor syndrome development

When modeling effects of hypogravitation by the method of hindlimb unloading in rats the area of cross-section in lumbar part of a spinal cord was found to reduce. The analysis of spinal cord slides showed that these changes are associated with a decrease in the area of white substance of a spinal cord. Data obtained are consistent with our previous observation of a decrease in expression of the genes encoding myelin proteins. Results of our researches give the good reasons to believe that miyelinization failure in CNS is one of the factors that underlie the development of hypogravitational motor syndrome.

Leptomeningeal seeding in patients with brain metastases treated by gamma knife radiosurgery

To characterize the development of leptomeningeal seeding (LMS) in patients with brain metastases after gamma knife radiosurgery (GKRS). Eight hundred and twenty-seven patients that underwent GKRS as a part of an initial treatment plan for brain metastases between January 2002 and December 2010 were included in the study. Six hundred and fifty patients were treated with GKRS alone and 177 patients received GKRS combined with upfront whole brain radiation therapy (WBRT). Actuarial curves for overall survival (OS) and the development of LMS were plotted using the Kaplan-Meier method. Median overall survival for all patients was 55 weeks (95 % CI, 47.8-62.2), and the overall incidence of LMS was 5.3 %. The actuarial rates for LMS at 6 and 12 months were 3.1 and 5.8, respectively. Uni- and multivariate analysis suggested that breast cancer and a large number of metastases (n ≥ 4) are significant risk factors of LMS (P < 0.05). Regarding treatment modalities, the addition of WBRT was found to have a significant impact on lowering the risk of LMS by multivariate analysis (P = 0.045). LMS is an important pattern of CNS failure. The risk of LMS following GKRS may be associated with multiple lesions, breast cancer, and the omission of WBRT. Additional data from large-scale, randomized controlled trials are required to identify risk factors associated with the LMS more accurately.

Withdrawal of Life-Sustaining Treatment in a Mixed Intensive Care Unit: Most Common in Patients with Catastropic Brain Injury

To determine the incidence of withdrawal of life-sustaining treatment in various groups of patients in a mixed intensive care unit (ICU). Observational retrospective. University hospital mixed medical, neurological, neurosurgical and surgical ICU. All patients admitted to the ICU between 1 November 2006, and 31 October 2007. 1,353 Patients were admitted to our ICU between 1 November 2006, and 31 October 2007. During this period, 218 (16.1%) patients died in the ICU, 10 of which were excluded for further analysis. In 174 (83.7%) of the remaining 208 patients, life-sustaining treatment was withdrawn. Severe CNS injury was in 86 patients (49.4%) being the reason for withdrawal of treatment, followed by MODS in 67 patients (38.5%). Notably, treatment was withdrawn in almost all patients (95%) who died of CNS failure. Patients who died in the ICU were significantly older, more often admitted for medical than surgical reasons, and had higher SOFA and APACHE II scores compared with those who survived their ICU stay. Also, SOFA scores before discharge/death were significantly different from admission scores. Of the 1,135 patients who survived their ICU stay, only 51 patients (4.5%) died within 28 days after ICU discharge. In 83, 7% of patients who die in the mixed ICU life-sustaining treatment is withdrawn. Severe cerebral damage was the leading reason to withdraw life-sustaining treatment.

Focused attention on brain metastases

Whole brain radiation therapy (WBRT) has been the standard means to manage brain metastases since the 1950s. Decades of research into fractionation, hypoxia, and radiation sensitisers has not changed this standard approach, which is applied uniformly for one or many metastases, and for tumours with varying radiosensitivity or responsiveness to systemic therapies. Digital imaging improved the diagnosis, treatment, and monitoring of brain metastases. We now know that resection or stereotactic radiosurgery (SRS) of single metastases improves survival when added to WBRT. 1–3 Technologies that enabled easy and repeated SRS for new or multiple metastases led to formal trials of SRS without WBRT. A recent Japanese trial assessed survival using SRS with or without WBRT for patients with one to four brain metastases. 4 Deferring WBRT did not compromise survival, and even though adding WBRT to SRS greatly reduced CNS failures compared with SRS alone, the neurocognitive outcomes were equivalent at 1 year. In this issue of The Lancet Oncology, Chang and colleagues 5 used a similar approach and population to examine neurocognitive outcomes as the primary endpoint. Signifi cant diff erences in learning and memory at 4 months and a substantial diff erence in survival that favoured SRS alone for one to three brain metastases were seen. Again, substantially more salvage procedures were used in the cohort that got SRS alone (83% vs 7%), but 61% of patients in the SRS alone group did not receive WBRT in the fi rst year following the diagnosis of brain metastases.

A phase I/II trial of irinotecan and whole brain radiation therapy in patients with brain metastases

1553 Background: Local CNS failure after whole brain radiation therapy (WBRT) is common for brain metastases. Irinotecan is a topoisomerase I-targeted drug with bioavailability in CNS. Irinotecan a...

Genetic deletion of the Nogo receptor does not reduce neurite inhibition in vitro or promote corticospinal tract regeneration in vivo

Axon regeneration failure in the adult mammalian CNS is attributed in part to the inhibitory nature of CNS myelin. Three myelin-associated, structurally distinct proteins, Nogo, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein, have been implicated in this inhibition. Neuronal Nogo receptor (NgR) binds to each of the three inhibitors and has been proposed to mediate their inhibitory signals by complexing with a signal-transducing coreceptor, the neurotrophin receptor p75(NTR). To assess the contribution of NgR to mediating myelin inhibitory signals and regeneration failure in vivo, we generated and characterized NgR-deficient mice. Nogo transcripts are up-regulated in NgR mutants, indicating that NgR regulates Nogo in vivo. However, neurite outgrowth from NgR-deficient postnatal dorsal root ganglion or cerebellar granule neurons is inhibited by myelin and by a Nogo-66 substrate to the same extent as is from wild-type neurons, whereas p75(NTR)-deficient neurons are less inhibited. The NgR ligand-binding domain promotes neurite outgrowth on Nogo-66, regardless of the genotype of the neurons, indicating that the NgR ligand-binding domain can act independent of NgR. Thus, NgR is not essential for mediating inhibitory signals from CNS myelin, at least in the neurons tested, whereas p75(NTR) plays a central role in this response. Neither NgR-nor p75(NTR)-deficient mice showed enhanced regeneration of corticospinal tract axons in comparison with wild-type controls after spinal dorsal hemisection. Our results thus fail to support a central role for NgR in axonal growth inhibition in vitro or in corticospinal tract regeneration block in vivo.

Intensity modulated radiation therapy for head and neck rhabdomyosarcoma

Intensity modulated radiation therapy for head and neck rhabdomyosarcoma

Role of cranial boost in addition to total body irradiation in the treatment of high risk acute lymphoblastic leukemia

Role of cranial boost in addition to total body irradiation in the treatment of high risk acute lymphoblastic leukemia

Degeneración de los terminales aferentes primarios de rata luego de lesión extensa por avulsión del plexo braquial

Important breakthroughs in the understanding regeneration failure in an injured CNS have been made by studies of primary afferent neurons. Dorsal rhizotomy has provided an experimental model of brachial plexus (BP) avulsion. This is an injury in which the central branches of primary afferents are disrupted at their point of entry into the spinal cord, bringing motor and sensory dysfunction to the upper limbs. In the present work, the central axonal organization of primary afferents was examined in control (without lesion) adult Wistar rats and in rats subjected to a C3-T3 rhizotomy. Specific sensory axon subtypes were recognized by application of antibodies to the calcitonin gene-related peptide (CGRP), the P2X3 purinoreceptor, the low-affinity p75-neurotrophin receptor and the retrograde tracer cholera toxin subunit beta (TCbeta). Other subtypes weres labeled with the lectin Griffonia simplicifolia 1B4. Using immunohistochemistry and high resolution light microscopy, brachial plexus rhizotomy in adult rats has proven a reliable model for several neural deficits in humans. This lesion produced different degrees of terminal degeneration in the several types of primary afferents which define sub-populations of sensitive neurons. Between the C6 and C8 levels of the spinal cord,, deafferentation was partial for peptidergic GCRP-positive fibers, in contrast with elimination of non peptidergic and myelinated fibers. Dorsal rhizotomy has provided an adequate experimental model to study sensory alterations such as acute pain and allodynia as well as factors that affect regeneration into the CNS., Therefore, the differential deafferentation response must be considered inr the evaluation of therapies for nociception (pain) and regeneration for brachial plexus avulsion. The anatomical diffierences among the primary afferent subtypes also affect their roles in normal and damaged conditions.

Deletion of the Parkin coregulated gene causes male sterility in the quaking(viable) mouse mutant.

Quaking(viable) (qk(v)) is a recessive neurological mouse mutation with severe dysmyelination of the CNS and spermiogenesis failure. The molecular lesion in the qk(v) mutant is a deletion of approximately 1 Mb on mouse chromosome 17 that alters the expression of the qk gene in oligodendrocytes. Complementation analysis between the qk(v) mutation and qk mutant alleles generated through chemical mutagenesis showed that the male sterility is a distinctive feature of the qk(v) allele. This observation suggested that the sperm differentiation defect in qk(v) is due to the deletion of a gene(s) distinct from qk. Here, we demonstrate that the deletion of Pacrg is the cause of male sterility in the qk(v) mutant. Pacrg is the mouse homologue of the human PARKIN-coregulated gene (PACRG), which encodes for a protein whose biochemical function remains unclear. We show that Pacrg is highly expressed in the testes in both mice and humans. In addition, the expression pattern of Pacrg during spermiogenesis suggests that it plays a role in sperm differentiation. In support of this hypothesis, we show that transgenic expression of Pacrg in testes restores spermiogenesis and fertility in qk(v) males. This finding provides the first in vivo evidence, to our knowledge, for the function of Pacrg in a model organism. Immunolocalization experiments on isolated spermatozoa show that the Pacrg protein is present in mature sperm. Remarkably, the mammalian Pacrg protein shares significant sequence similarities with gene products from flagellated protozoans, suggesting that Pacrg may be necessary for proper flagellar formation in many organisms.

A novel primary culture technique for adult retina allows for evaluation of CNS axon regeneration in rodents

Unraveling the causes of regeneration failure in the adult injured CNS has remained a challenge in neurobiology. The notion that CNS neurons lose their regenerative potential during development has been challenged by the identification of several promoters of axon growth. Novel methods are required that allow to study and quantify interactions of molecular determinants, and to envisage future treatment applications. Here we report a novel, highly reproducible method for monitoring axonal regeneration of mature retinal ganglion cells (RGCs) in vitro. In contrast to earlier explantation methods, primary cultures derived from adult rodent retina are kept viable without growth factor supplements. Further, since intraretinal RGC axons remain unmyelinated, regeneration can be followed independently of non-permissive white matter compounds. Applying tracing techniques prior to retinal explantation, cell survival can be correlated to outgrowth activity on the single cell level. Following intervention with pharmacological, growth factor, or gene transfer treatments, retinal explants, and partially RGC neurites, can be processed for protein and gene expression analysis. This novel procedure will prove useful to get insight into complex cell survival and regeneration promoting cascades, and will complement in vivo strategies such as transgenic and knock out mouse models.

The Changing Face of Organ Failure in ARDS

To study morbidity and mortality in ARDS patients from 1987 to 1999. Review of a prospectively collected database of ARDS patients. Large, community hospital located in Salt Lake City, UT. ARDS patients identified for the years 1987 to 1999. We prospectively identified ARDS patients at LDS Hospital in Salt Lake City, UT, using PaO(2)/fraction of inspired oxygen ratio (P/F) criteria, the presence of bilateral chest radiograph infiltrates, and the absence of left atrial hypertension. We assigned a primary risk factor for ARDS and identified the presence of organ failure before and after ARDS. We compared two temporal groups (ie, 1987 to 1990 vs 1994 to 1999) and used two criteria of arterial hypoxemia (P/F: patients from 1994 to 1999, < or = 105 and < or = 173; patients from 1987 to 1990, < or = 0.2) At 1,500 m (the altitude of Salt Lake City), a PaO(2) of < or = 173 corresponds to an alveolar-arterial oxygen pressure difference of < or = 200 at sea level. We used death at hospital discharge as an end point. We identified 516 ARDS patients with a P/F of < or = 105 (1987 to 1990, 256 patients; 1994 to 1999, 260 patients). Patients who had ARDS between 1994 and 1999 with a P/F of < or = 105 had a lower mortality rate than patients between 1987 and 1990 with a P/F of < or = 105 (44% vs 54%, respectively; p <.05). There were 288 patients with a P/F range of 106 to 173 during 1994 to 1999. Patients from 1994 to 1999 with a P/F of < or = 173 had a lower mortality rate compared to patients from 1987 to 1990 (35% vs 54%, respectively; p <.01). Patients from 1994 to 1999 (for both P/F groups) had statistically fewer total nonpulmonary organ failures (ie, more patients had zero organ failures or single organ failures) and fewer specific organ failures (ie, sepsis, cardiovascular failures, and CNS failures). There were statistically fewer cases of cardiovascular failure, sepsis, and in both periods (ie, prior to ARDS and after the onset of ARDS) for 1994-to-1999 patients with a P/F of < or = 105 compared to 1987-to-1990 patients with a P/F of < or = 105. Mortality from ARDS has decreased and is associated with decreased organ failure prior to and during the course of ARDS.

Radiation therapy for brain metastases from breast cancer.

Breast cancer is one of the most common malignancies that metastasize to the brain. Radiation therapy plays a central role in the management of brain metastases. The medical records of 36 patients with brain metastases from breast cancer who underwent whole-brain radiation therapy (WBRT) at Kyoto University Hospital between 1993 and 2001 were reviewed. The treatment outcomes were analyzed retrospectively. The median age at the time of diagnosis of brain metastases was 52 years. Only 4 patients (11%) had a single metastasis, while the others had multiple metastases. Uncontrolled extracranial metastases were present in 26 patients at the time of diagnosis of brain metastases. All patients received WBRT at a median dose of 31 Gy. Eight patients received conventional external-beam boost irradiation, and 2 received boost stereotactic radiosurgery (SRS). The overall median survival time was 7.9 months. Uncontrolled extracranial metastases except for bone metastases and old age were significantly associated with a poor survival rate. Twenty-six patients (82%) showed initial response, but 15 developed CNS failure, including 9 patients whose tumor recurred at the original site, 4 patients who developed tumors elsewhere in the brain and 3 patients who exhibited meningeal spread. The median duration of intracranial failure was 5.0 months. Whole-brain dose, and total tumor dose did not affect intracranial control. Radiation therapy yielded a high initial response, but the duration of effect was limited with external beam irradiation alone. New treatment strategies such as adding SRS need to be studied further.

Therapy of non-Hodgkin's lymphoma.

Non-Hodgkin's lymphomas are a heterogeneous group of malignancies of the lymphoid system. The exact etiology for most lymphomas has not been determined, but both viral and bacterial infections have been shown to be important etiologic factors. The WHO classification of hematopoietic and lymphoid tumours classifies lymphomas into B-cell and T-cell neoplasms. B-cell lymphomas account for more than 85% of all lymphomas. The Ann Arbor staging classification has been adopted by the AJCC and UICC as a standard for classifying extent of anatomic disease. The two most common histologic disease entities are follicular lymphomas and diffuse large B-cell lymphomas. The management of follicular lymphomas is used as a paradigm for the management of all indolent lymphomas. Radiation therapy is used for stage I and II disease, while alkylating agent chemotherapy, immunotherapy and radioimmunotherapy are most frequently used in stage III and IV disease that requires treatment. Most patients with follicular lymphoma enjoy prolonged survival, but at present there is no evidence that those with stage III and IV follicular lymphoma can be cured. Diffuse large B-cell lymphomas serve as a paradigm for treating aggressive lymphomas. Stage I and II diffuse large cell lymphomas are generally treated with combined modality therapy with doxorubicin-based chemotherapy followed by involved field radiation therapy, while those with stage III and IV disease are treated with chemotherapy alone. Patients who fail initial management are treated with further chemotherapy. High-dose chemotherapy with stem cell rescue has been shown to be particularly effective as salvage treatment for diffuse large cell lymphomas. The management of a heterogeneous group of primary extranodal lymphomas in general follows the above treatment principles, with additional treatment being required for those with a high risk of CNS failures, or involvement of contralateral paired organs. The management of MALT lymphomas, especially gastric MALT lymphoma, deserves special attention because of the high response rate to Helicobacter pylori eradication therapy.

Treatment outcome for patients with primary nonsmall-cell lung cancer and synchronous brain metastasis.

The purpose of this study was to evaluate the outcome of treatment for patients with newly diagnosed nonsmall-cell lung cancer (NSCLC) with an isolated, single, synchronous brain metastasis. A retrospective review was performed evaluating any patient diagnosed between 1982 and 1996 at the Cleveland Clinic Foundation with NSCLC metastatic only to the brain. Patients with multiple brain metastases or with systemic metastases to any other organ were excluded. Survival was measured from the date of the first treatment for malignancy. All hospital records were thoroughly reviewed in a retrospective manner. Thirty-three patients were identified who met the study criteria. Twelve patients had primary disease limited to the lung and hilar nodes, and 21 had more advanced primary disease with involvement of the mediastinum. Treatment of the chest was considered aggressive in 13 patients and palliative in 15. The primary tumor was observed in 5 patients. The management of the brain metastasis was as follows: 21 patients underwent surgical resection and postoperative whole brain radiotherapy (WBRT), 5 underwent stereotactic radiosurgery (SRS) and WBRT, 3 had resection alone, 2 had SRS alone, and 2 underwent WBRT alone. The median overall and disease-free survival for all patients was 6.9 months and 3.3 months, respectively. Overall survival was markedly improved with the addition of WBRT (P = 0.002) and with the aggressive management of the primary tumor (P = 0.005). A total of 9 patients experienced CNS failure, including both patients receiving WBRT alone. CNS failures were divided as follows: 3 local, 5 distant, and 1 local and distant. Two of the 4 patients with a local failure were salvaged, and ultimate local control of the original brain metastasis was achieved in 93.6% of cases. Survival remains poor for patients with Stage IV NSCLC even when metastatic disease is limited to a single site within the brain; however, aggressive therapy of both the lung primary and the brain metastasis may provide a survival advantage. Excellent local control of single brain metastases was achieved with a combination of WBRT with either surgical resection or SRS.

Treatment outcome for patients with primary nonsmall‐cell lung cancer and synchronous brain metastasis

The purpose of this study was to evaluate the outcome of treatment for patients with newly diagnosed nonsmall-cell lung cancer (NSCLC) with an isolated, single, synchronous brain metastasis. A retrospective review was performed evaluating any patient diagnosed between 1982 and 1996 at the Cleveland Clinic Foundation with NSCLC metastatic only to the brain. Patients with multiple brain metastases or with systemic metastases to any other organ were excluded. Survival was measured from the date of the first treatment for malignancy. All hospital records were thoroughly reviewed in a retrospective manner. Thirty-three patients were identified who met the study criteria. Twelve patients had primary disease limited to the lung and hilar nodes, and 21 had more advanced primary disease with involvement of the mediastinum. Treatment of the chest was considered aggressive in 13 patients and palliative in 15. The primary tumor was observed in 5 patients. The management of the brain metastasis was as follows: 21 patients underwent surgical resection and postoperative whole brain radiotherapy (WBRT), 5 underwent stereotactic radiosurgery (SRS) and WBRT, 3 had resection alone, 2 had SRS alone, and 2 underwent WBRT alone. The median overall and disease-free survival for all patients was 6.9 months and 3.3 months, respectively. Overall survival was markedly improved with the addition of WBRT (P = 0.002) and with the aggressive management of the primary tumor (P = 0.005). A total of 9 patients experienced CNS failure, including both patients receiving WBRT alone. CNS failures were divided as follows: 3 local, 5 distant, and 1 local and distant. Two of the 4 patients with a local failure were salvaged, and ultimate local control of the original brain metastasis was achieved in 93.6% of cases. Survival remains poor for patients with Stage IV NSCLC even when metastatic disease is limited to a single site within the brain; however, aggressive therapy of both the lung primary and the brain metastasis may provide a survival advantage. Excellent local control of single brain metastases was achieved with a combination of WBRT with either surgical resection or SRS. Radiat. Oncol. Invest. 7:313–319, 1999. © 1999 Wiley-Liss, Inc.