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PURPOSE/OBJECTIVE(S): Brain metastasis velocity (BMV) is a metric that describes the rate of development of new brain metastases (BM) after initial stereotactic radiosurgery (SRS). A limitation in the application of BMV is it cannot be applied until time of first BM failure after SRS. We developed initial BM velocity (iBMV), a new metric that accounts for the number of BM at first SRS and the time since initial cancer diagnosis. MATERIALS/METHODS: We reviewed patients with BM treated at our institution with upfront SRS without WBRT. iBMV was calculated as the number of BM at initial SRS divided by time (years) from initial cancer diagnosis to first SRS. We performed a linear regression to correlate BMV as a continuous variable and with low, intermediate, and high BMV risk groups. Kaplan-Meier estimation of OS was calculated from time of first SRS to death. iBMV was not calculated for patients who presented with BM at initial cancer diagnosis. RESULTS: 994 patients were treated with upfront SRS without WBRT between 2000 and 2017. Median OS was 8.5 mos. 595 (60%) patients developed BM after cancer diagnosis and median time to first SRS from time of initial diagnosis was 2.2 years. Median iBMV was 0.79 BM/year. iBMV correlated with BMV (ß = 1.57 p = 0.021) and independently predicted for mortality [Cox proportional hazard ratio (HR) 1.11, p = 0.036] after accounting for histology, number of initial brain metastases (HR 1.03, p = 0.32), time from cancer diagnosis to SRS (HR 0.98, p = 0.157) in a multivariate model. CONCLUSION: iBMV correlates with BMV and OS. With further validation, iBMV could serve as a metric to risk stratify patients for WBRT or SRS at time of first BM presentation.
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Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Neoplasias/mortalidade , Neoplasias/patologia , Radiocirurgia/mortalidade , Idoso , Neoplasias Encefálicas/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
PURPOSE: For glioblastoma (GBM), imaging response (IR) or pseudoprogression (PSP) is frequently observed after chemoradiation and may connote a favorable prognosis. With tumors categorized by the Cancer Genome Atlas Project (mesenchymal, classical, neural, and proneural) and by methylguanine-methyltransferase (MGMT) methylation status, we attempted to determine if certain genomic or molecular subtypes of GBM were specifically associated with IR or PSP. METHODS: Patients with GBM treated at two institutions were reviewed. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Mantel-cox test determined effect of IR and PSP on OS and PFS. Fisher's exact test was utilized to correlate IR and PSP with genomic subtypes and MGMT status. RESULTS: Eighty-two patients with GBM were reviewed. The median OS and PFS were 17.9 months and 8.9 months. IR was observed in 28 (40%) and was associated with improved OS (median 29.4 vs 14.5 months p < 0.01) and PFS (median 17.7 vs 5.5 months, p < 0.01). PSP was observed in 14 (19.2%) and trended towards improved PFS (15.0 vs 7.7 months p = 0.08). Tumors with a proneural component had a higher rate of IR compared to those without a proneural component (IR 60% vs 28%; p = 0.03). MGMT methylation was associated with IR (58% vs 24%, p = 0.032), but not PSP (34%, p = 0.10). CONCLUSION: IR is associated with improved OS and PFS. The proneural subtype and MGMT methylated tumors had higher rates of IR.
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Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Genômica , Glioblastoma/diagnóstico por imagem , Glioblastoma/genética , Glioblastoma/terapia , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND/AIMS: Brain metastases from bladder cancer are rare and published outcomes data are sparse. To date, no institutions have reported a series of patients with brain metastases from bladder cancer treated with stereotactic radiosurgery (SRS). Our aim was to identify patients with brain metastases from bladder primaries treated with SRS with or without surgical resection and report the clinical outcomes. METHODS: Patients meeting eligibility criteria at our institution between 2000 and 2017 were included. The clinical variables of interest, including overall survival (OS), local recurrence, V12, distant brain failure (DBF), and initial brain metastases velocity, were calculated. Cox proportional hazards analysis was performed to identify predictors of time-to-event outcomes. RESULTS: A total of 14 patients were included. The median OS from the time of treatment was 2.1 months. Factors predictive of OS include intracranial resection (HR 0.21, p = 0.03). The cumulative incidence of local failure was 21% at 6 months and 30% at 12 months. The cumulative incidence of DBF at 6 and 12 months was 23 and 31%, respectively. CONCLUSIONS: The prognosis in this patient population remains guarded. Factors associated with improved survival include intracranial resection. Future, prospective work is needed to further define optimal management.
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Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Radiocirurgia/métodos , Neoplasias da Bexiga Urinária/radioterapia , Idoso , Neoplasias Encefálicas/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/radioterapia , Estudos Prospectivos , Estudos Retrospectivos , Terapia de Salvação/métodos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/diagnósticoRESUMO
Background: Leptomeningeal failure (LMF) represents a devastating progression of disease following resection of brain metastases (BrM). We sought to identify a biomarker at time of BrM resection that predicts for LMF using mass spectrometry-based proteomic analysis of resected BrM and to translate this finding with histochemical assays. Methods: We retrospectively reviewed 39 patients with proteomic data available from resected BrM. We performed an unsupervised analysis with false discovery rate adjustment (FDR) to compare proteomic signature of BrM from patients that developed LMF versus those that did not. Based on proteomic analysis, we applied trichrome stain to a total of 55 patients who specifically underwent resection and adjuvant radiosurgery. We used competing risks regression to assess predictors of LMF. Results: Of 39 patients with proteomic data, FDR revealed type I collagen-alpha-1 (COL1A1, Pâ =â .045) was associated with LMF. The degree of trichrome stain in each block correlated with COL1A1 expression (ßâ =â 1.849, Pâ =â .001). In a cohort of 55 patients, a higher degree of trichrome staining was associated with an increased hazard of LMF in resected BrM (Hazard Ratio 1.58, 95% CI 1.11-2.26, Pâ =â .01). Conclusion: The degree of trichrome staining correlated with COL1A1 and portended a higher risk of LMF in patients with resected brain metastases treated with adjuvant radiosurgery. Collagen deposition and degree of fibrosis may be able to serve as a biomarker for LMF.
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Purpose To determine the efficacy and toxicity of two standard chemotherapy regimens used concurrent with radiation for the treatment of esophageal cancer: cisplatin/5-fluorouracil (5-FU) and carboplatin/paclitaxel. Materials and methods We prospectively reviewed records of 364 patients with histologically confirmed stage I to IVA esophageal cancer receiving chemoradiotherapy (CRT) with or without resection. All patients received surgical evaluation and imaging at presentation as well as following completion of their course of CRT. Treatment and prognostic variables were compared across the two chemotherapy regimens. Results We identified 261 patients treated with concurrent carboplatin/paclitaxel (n = 133) or cisplatin/5-FU (n = 128). Weight loss during CRT was lower in patients receiving carboplatin/paclitaxel (median: 7.0 pounds; 4.1% body weight) vs. cisplatin/5-FU (median: 11.0 pounds; 6.5% body weight) (p < 0.01). In 117 patients receiving trimodality therapy, post-operative death rates within one month of resection were similar. Pathologic complete response was better with carboplatin/paclitaxel vs. cisplatin/5-FU, 29.6% vs. 21.8% (p = 0.03), respectively. In the multivariable analysis, there was no association between chemotherapy regimen and overall survival (OS) or progression-free survival (PFS), though there was a trend toward improved OS with carboplatin/paclitaxel with a HR = 0.75 (p = 0.08). Further analysis revealed that trimodality therapy and stage were predictors for improved OS and PFS while female gender and grade predicted for improved PFS. Conclusions Carboplatin/paclitaxel was associated with decreased weight loss and improved pathologic response for trimodality patients when compared to cisplatin/5-FU. We observed no differences in OS, PFS, or post-operative death by chemotherapy regimen for both the entire cohort and trimodality patients.
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INTRODUCTION: Brain metastasis velocity (BMV) is a prognostic metric that describes the recurrence rate of new brain metastases after initial treatment with radiosurgery (SRS). We have previously risk stratified patients into high, intermediate, and low-risk BMV groups, which correlates with overall survival (OS). We sought to externally validate BMV in a multi-institutional setting. METHODS: Patients from nine academic centers were treated with upfront SRS; the validation cohort consisted of data from eight institutions not previously used to define BMV. Patients were classified by BMV into low (<4 BMV), intermediate (4-13 BMV), and high-risk groups (>13 BMV). Time-to-event outcomes were estimated using the Kaplan-Meier method. Cox proportional hazards methods were used to estimate the effect of BMV and salvage modality on OS. RESULTS: Of 2829 patients, 2092 patients were included in the validation dataset. Of these, 921 (44.0%) experienced distant brain failure (DBF). Median OS from initial SRS was 11.2 mo. Median OS for BMVâ¯<â¯4, BMV 4-13, and BMVâ¯>â¯13 were 12.5 mo, 7.0 mo, and 4.6 mo (pâ¯<â¯0.0001). After multivariate regression modeling, melanoma histology (ß: 10.10, SE: 1.89, pâ¯<â¯0.0001) and number of initial brain metastases (ß: 1.52, SE: 0.34, pâ¯<â¯0.0001) remained predictive of BMV (adjusted R2â¯=â¯0.06). CONCLUSIONS: This multi-institutional dataset validates BMV as a predictor of OS following initial SRS. BMV is being utilized in upcoming multi-institutional randomized controlled trials as a stratification variable for salvage whole brain radiation versus salvage SRS after DBF.
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Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Radiocirurgia/métodos , Idoso , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias/patologia , Neoplasias/radioterapia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Terapia de Salvação/métodosRESUMO
Stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) are effective treatments for management of brain metastases. Prospective trials comparing the 2 modalities in patients with fewer than 4 brain metastases demonstrate that overall survival (OS) is similar. Intracranial failure is more common after SRS, while WBRT is associated with neurocognitive decline. As technology has advanced, fewer technical obstacles remain for treating patients with 4 or more brain metastases with SRS, but level I data supporting its use are lacking. Observational prospective studies and retrospective series indicate that in patients with 4 or more brain metastases, performance status, total volume of intracranial disease, histology, and rate of development of new brain metastases predict outcomes more accurately than the number of brain metastases. It may be reasonable to initially offer SRS to some patients with 4 or more brain metastases. Initiating therapy with SRS avoids the acute and late sequelae of WBRT. Multiple phase III trials of SRS vs WBRT, both currently open or under development, are directly comparing quality of life and OS for patients with 4 or more brain metastases to help answer the question of SRS appropriateness for these patients.
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Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Radiocirurgia/métodos , Neoplasias Encefálicas/diagnóstico , Ensaios Clínicos como Assunto/métodos , Irradiação Craniana , Gerenciamento Clínico , Progressão da Doença , Humanos , Estudos Prospectivos , Qualidade de Vida , Radiocirurgia/mortalidade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Metastatic prostate cancer has a 5-year survival rate of 30%. Identifying predictors of metastasis outcome could potentially reduce patient mortality. The objective of this study was to determine whether osteoarthritis had an impact on outcomes of prostate cancer including death, local recurrence and/or metastasis and to determine whether cartilage oligomeric matrix protein was involved. We performed a retrospective case-control study of patients with prostate cancer with and without the diagnosis of osteoarthritis and completed immunohistochemistry (IHC) analysis of prostate (n=20) and lymph node (n=7) surgical specimens. We evaluated death, local recurrence and metastatic disease by various IHC biomarkers including prostate specific membrane antigen (PSMA), cartilage oligomeric matrix protein (COMP), CD31, and Ki-67. Our model identified osteoarthritis as an independent risk factor for metastatic disease (OR 5.24, 95% CI 1.49 - 18.41). Most notably, when joint arthroplasty was included in the model, osteoarthritis was no longer an independent risk factor for this outcome (p=0.071). IHC demonstrated that those with osteoarthritis, had greater expression of COMP in the prostate samples (mean 23.9% vs 5.84%, p<0.05) but not of Ki-67, CD31, or PSMA. This study identified and quantified increased metastatic disease in patients with osteoarthritis. Also, patients with osteoarthritis expressed increased COMP levels in the prostate and most likely in distant lymphatic nodes. Moreover, our findings suggest that joint arthroplasty may affect the ability of osteoarthritis to promote metastasis, which could impact treatment protocols and survival outcomes of the most common cause of cancer-related death (metastasis) in the United States.
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BACKGROUND: The role of primary stereotactic radiosurgery (SRS) for patients with >4 brain metastases (BM) remains controversial. OBJECTIVE: To compare the outcomes of patients treated with upfront SRS alone for 1, 2 to 4, and 5 to 15 BM and assess for predictors of clinical outcomes in the 5 to 15 BM group. METHODS: A total of 478 patients treated with upfront SRS were stratified by number of lesions: 220 had 1 BM, 190 had 2 to 4 BM, and 68 patients had 5 to 15 BM. Overall survival and whole brain radiotherapy-free survival were estimated using the Kaplan-Meier method. The cumulative incidences of local failure and distant brain failure (DBF) were estimated using competing risks methodology. Clinicopathologic and dosimetric parameters were evaluated as predictors of survival and DBF in patients with 5 to 15 BM using Cox proportional hazards. RESULTS: Median overall survival was 8.0, 6.3, and 4.7 mo for patients with 1, 2 to 4, and 5 to 15 BM, respectively (P = .14). One-year DBF was 27%, 44%, and 40%, respectively (P = .01). Salvage SRS and whole brain radiotherapy rates did not differ. Progressive extracranial disease and gastrointestinal primary were associated with poor survival while RCC primary was associated with increased risk of DBF. No evaluated dose-volume parameters predicted for death, neurologic death or toxicity. CONCLUSION: SRS for 5 to 15 BM is well tolerated without evidence of an associated increase in toxicity, treatment failure, or salvage therapy. Further prospective, randomized studies are warranted to clarify the role of SRS for these patients.
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Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Radiocirurgia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiocirurgia/mortalidade , Resultado do TratamentoRESUMO
PURPOSE/OBJECTIVES: We aimed to assess the predictive value of a lung cancer gene panel for the development of brain metastases. MATERIALS/METHODS: Between 2011 and 2015, 102 patients with lung cancer were prospectively enrolled in a clinical trial in which a diagnostic fine-needle aspirate was obtained. Gene expression was conducted on all samples that rendered a diagnosis of non-small cell lung cancer (NSCLC). Subsequent retrospective analysis of brain metastases-related outcomes was performed by reviewing patient electronic medical records. A competing risk multivariable regression was performed to estimate the adjusted hazard ratio for the development of brain metastases and non-brain metastases from NSCLC. RESULTS: A total of 49 of 102 patients had died by the last follow-up. Median time of follow-up was 13 months (range 0.23-67 months). A total of 17 patients developed brain metastases. Median survival time after diagnosis of brain metastases was 3.58 months (95% confidence interval (CI) 2.17, not available). A total of 30 patients developed metastases without any evidence of brain metastases until the time of death or last follow-up. Competing risk analysis identified three genes that were downregulated differentially in the patients with brain metastases versus non-brain metastatic disease: CD37 (0.017), cystatin A (0.022), and IL-23A (0.027). Other factors associated with brain metastases include: stage T ( P ⩽ 8.3e-6) and stage N ( P= 6.8e-4). CONCLUSIONS: We have identified three genes, CD37, cystatin A, and IL-23A, for which downregulation of gene expression was associated with a greater propensity for developing brain metastases. Validation of these biomarkers could have implications on surveillance patterns in patients with brain metastases from NSCLC.
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Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/patologia , Cistatina A/metabolismo , Subunidade p19 da Interleucina-23/metabolismo , Neoplasias Pulmonares/patologia , Tetraspaninas/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/secundário , Idoso , Neoplasias Encefálicas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundário , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
OBJECTIVES: We aimed to assess the driving factors for increased cost of brain metastasis management when using upfront stereotactic radiosurgery (SRS). PATIENT AND METHODS: 737 patients treated with upfront SRS without whole brain radiotherapy (WBRT). Patients were evaluated for use of craniotomy, length of hospital stay, need for rehabilitation or facility placement, and use of salvage SRS or salvage WBRT. Costs of care of these interventions were estimated based on 2013 Medicare reimbursements. Multiple linear regression was performed to determine factors that predicted for higher cost of treatment per month of life, as well as highest cumulative cost of care for brain metastasis. RESULTS: Mean cost of brain metastasis management per patient was $42,658, and $4673 per month of life. Upfront SRS represented the greatest contributor of total cost of brain metastasis management over a lifetime (49%), followed by use of any salvage SRS (21%), use of initial surgery (14%), use of salvage surgery (10%), hospitalization (3%) and cost of salvage WBRT (3%). Multiple linear regression identified brain metastasis velocity (BMV) (p < 0.001), use of cavity-directed SRS (<0.001), and CNS symptoms at time of presentation (p = 0.005) as factors that increased costs of care per month of survival. Use of salvage WBRT decreased per month cost of care in patients requiring salvage (p < 0.001). CONCLUSION: The cost of upfront SRS is the greatest contributor to cost of brain metastasis management when using upfront SRS. Higher BMV, progressive systemic disease and presence of symptoms are associated with increased cost of care.
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Neoplasias Encefálicas/cirurgia , Custos e Análise de Custo , Medicare/economia , Radiocirurgia/economia , Idoso , Irradiação Craniana/economia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Salvação/economia , Estados UnidosRESUMO
PURPOSE: Several studies evaluating stereotactic radiosurgery (SRS) for patients with >4 brain metastases (BM) demonstrated similar outcomes after treatment of 1, 2 to 4, and 5 to 15 BM; others found clinically significant survival decrements in the latter group. In this review of 8 academic centers, we compared outcomes of patients undergoing initial SRS for 1, 2 to 4, and 5 to 15 BM. METHODS AND MATERIALS: A total of 2089 patients treated with initial SRS for BM were included. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Patient and disease characteristics were evaluated for association with OS and cumulative incidence of distant brain failure (DBF) using stepwise multivariable Cox proportional hazards and competing risk regression modeling. RESULTS: In this series, 989 (47%) patients had 1 metastasis, 882 (42%) had 2 to 4 metastases, and 212 (10%) had 5 to 15 metastases treated. Median OS for the 1, 2 to 4, and 5 to 15 BM groups was 14.6, 9.5, and 7.5 months, respectively (log-rank P < .01). Univariate and multivariable analyses revealed no difference in survival between 2 to 4 and 5 to 15 BM. DBF at 1 year was 30%, 41%, and 50%, respectively (Gray's P < .01). Two-year cumulative incidence of salvage SRS decreased with increasing number of BM (1: 21% vs 2-4: 19% vs 5-15: 13%; P < .01), but no difference in salvage whole brain radiation therapy was observed (1: 12% vs 2-4: 15% vs 5-15: 16%, P = .10). At the time of DBF, median brain metastasis velocity was 3.9, 6.1, and 11.7 new metastases per year in the 1, 2 to 4, and 5 to 15 BM groups, respectively (P < .01). CONCLUSIONS: Patients treated with initial SRS for 5 to 15 BM experienced survival similar to that in patients with 2 to 4 BM. Lower rates of salvage SRS were observed in the 5 to 15 BM group, with no difference in rates of salvage whole brain radiation therapy.
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Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Radiocirurgia/métodos , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Irradiação Craniana/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Radiocirurgia/mortalidade , Terapia de Salvação/estatística & dados numéricos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Stereotactic body radiation therapy (SBRT) is associated with an increased risk of vertebral compression fracture. While bone is typically considered radiation resistant, fractures frequently occur within the first year of SBRT. The goal of this work was to determine if rapid deterioration of bone occurs in vertebrae after irradiation. Sixteen male rhesus macaque non-human primates (NHPs) were analyzed after whole-chest irradiation to a midplane dose of 10 Gy. Ages at the time of exposure varied from 45-134 months. Computed tomography (CT) scans were taken 2 months prior to irradiation and 2, 4, 6 and 8 months postirradiation for all animals. Bone mineral density (BMD) and cortical thickness were calculated longitudinally for thoracic (T) 9, lumbar (L) 2 and L4 vertebral bodies; gross morphology and histopathology were assessed per vertebra. Greater mortality (related to pulmonary toxicity) was noted in NHPs <50 months at time of exposure versus NHPs >50 months ( P = 0.03). Animals older than 50 months at time of exposure lost cortical thickness in T9 by 2 months postirradiation ( P = 0.0009), which persisted to 8 months. In contrast, no loss of cortical thickness was observed in vertebrae out-of-field (L2 and L4). Loss of BMD was observed by 4 months postirradiation for T9, and 6 months postirradiation for L2 and L4 ( P < 0.01). For NHPs younger than 50 months at time of exposure, both cortical thickness and BMD decreased in T9, L2 and L4 by 2 months postirradiation ( P < 0.05). Regions that exhibited the greatest degree of cortical thinning as determined from CT scans also exhibited increased porosity histologically. Rapid loss of cortical thickness was observed after high-dose chest irradiation in NHPs. Younger age at time of exposure was associated with increased pneumonitis-related mortality, as well as greater loss of both BMD and cortical thickness at both in- and out-of-field vertebrae. Older NHPs exhibited rapid loss of BMD and cortical thickness from in-field vertebrae, but only loss of BMD in out-of-field vertebrae. Bone is sensitive to high-dose radiation, and rapid loss of bone structure and density increases the risk of fractures.
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Osso Cortical/anatomia & histologia , Osso Cortical/efeitos da radiação , Animais , Densidade Óssea/efeitos da radiação , Osso Cortical/diagnóstico por imagem , Osso Cortical/fisiologia , Vértebras Lombares/anatomia & histologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/fisiologia , Vértebras Lombares/efeitos da radiação , Macaca mulatta , Masculino , Tamanho do Órgão/efeitos da radiação , Vértebras Torácicas/anatomia & histologia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/fisiologia , Vértebras Torácicas/efeitos da radiação , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Treatment options are limited for large, unresectable brain metastases. OBJECTIVE: To report a single institution series of staged stereotactic radiosurgery (SRS) that allows for tumor response between treatments in order to optimize the therapeutic ratio. METHODS: Patients were treated with staged SRS separated by 1 mo with a median dose at first SRS of 15 Gy (range 10-21 Gy) and a median dose at second SRS of 14 Gy (range 10-18 Gy). Overall survival was evaluated using the Kaplan-Meier method. Cumulative incidences were estimated for neurological death, radiation necrosis, local failure (marginal or central), and distant brain failure. Absolute cumulative dose-volume histogram was created for each treated lesion. Logistic regression and competing risks regression were performed for each discrete dose received by a certain volume. RESULTS: Thirty-three patients with 39 lesions were treated with staged radiosurgery. Overall survival at 6 and 12 mo was 65.0% and 60.0%, respectively. Cumulative incidence of local failure at 6 and 12 mo was 3.2% and 13.3%, respectively. Of the patients who received staged therapy, 4 of 33 experienced local failure. Radiation necrosis was seen in 4 of 39 lesions. Two of 33 patients experienced a Radiation Therapy Oncology Group toxicity grade > 2 (2 patients had grade 4 toxicities). Dosimetric analysis revealed that dose (Gy) received by volume of brain (ie, VDose(Gy)) was associated with radiation necrosis, including the range V44.5Gy to V87.8Gy. CONCLUSION: Staged radiosurgery is a safe and effective option for large, unresectable brain metastases. Prospective studies are required to validate the findings in this study.
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Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Metástase Neoplásica/terapia , Radiocirurgia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Radiocirurgia/mortalidade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE/OBJECTIVES: Stereotactic radiosurgery (SRS) is used as a treatment option for breast cancer brain metastases. It is unclear what factors predict neurologic death for these patients. MATERIALS/METHODS: A total of 128 patients with breast cancer brain metastases were treated with upfront SRS alone in this study. Survival was estimated using the Kaplan-Meier method. Clinicopathologic factors evaluated included age, ER/PR status, Her2 status, numbers of brain metastases treated, minimum SRS dose, disease-specific GPA, extracranial disease status and systemic disease burden. RESULTS: ER or PR positivity was associated with a trend towards decreased neurologic death (subdistribution hazard ratio (sHR) = 0.54, p=0.06). Factors associated with non-neurologic death include extracranial disease status (sHR = 2.02, p=0.02) and dose (sHR = 1.11, p=0.02); Her2-positivity was associated with reduced hazard of non-neurologic death (sHR 0.52, p=0.05). CONCLUSIONS: ER/PR positivity was associated with a trend towards less neurologic death. HER2 positivity was associated with a trend towards less non-neurologic death.
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PURPOSE: To determine the influence of diabetes mellitus (DM) on outcomes in patients with brain metastasis treated with stereotactic radiosurgery (SRS). METHODS: We retrospectively reviewed 498 patients with brain metastasis treated at our institution with SRS between January 2012 and March 2017. RESULTS: Eight-four patients (16.9%) held a diagnosis of DM prior to SRS treatment. Diabetics compared to nondiabetics had worse overall survival (OS). DM was found to be a significant predictor of OS on multivariate analysis (HR: 1.41, CI: 1.03-1.92, p = 0.03). When stratified by DM diagnosis, there were no significant differences in incidence of radiation necrosis (p = 0.82), radiation-induced edema (p = 0.88), cerebrospinal fluid leak (p = 0.49), or postoperative infection (p = 0.68). CONCLUSIONS: DM diagnosis was a significant predictor of poorer OS in patients treated for brain metastasis with SRS. Diabetics and nondiabetics experienced similar rates of radiation-associated brain toxicities.
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Background: In this study we attempted to discern the factors predictive of neurologic death in patients with brain metastasis treated with upfront stereotactic radiosurgery (SRS) without whole brain radiation therapy (WBRT) while accounting for the competing risk of nonneurologic death. Methods: We performed a retrospective single-institution analysis of patients with brain metastasis treated with upfront SRS without WBRT. Competing risks analysis was performed to estimate the subdistribution hazard ratios (HRs) for neurologic and nonneurologic death for predictor variables of interest. Results: Of 738 patients treated with upfront SRS alone, neurologic death occurred in 226 (30.6%), while nonneurologic death occurred in 309 (41.9%). Multivariate competing risks analysis identified an increased hazard of neurologic death associated with diagnosis-specific graded prognostic assessment (DS-GPA) ≤ 2 (P = .005), melanoma histology (P = .009), and increased number of brain metastases (P<.001), while there was a decreased hazard associated with higher SRS dose (P = .004). Targeted agents were associated with a decreased HR of neurologic death in the first 1.5 years (P = .04) but not afterwards. An increased hazard of nonneurologic death was seen with increasing age (P =.03), nonmelanoma histology (P<.001), presence of extracranial disease (P<.001), and progressive systemic disease (P =.004). Conclusions: Melanoma, DS-GPA, number of brain metastases, and SRS dose are predictive of neurologic death, while age, nonmelanoma histology, and more advanced systemic disease are predictive of nonneurologic death. Targeted agents appear to delay neurologic death.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/radioterapia , Radiocirurgia , Idoso , Neoplasias Encefálicas/secundário , Irradiação Craniana , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND AND PURPOSE: Anal cancer patients treated with radiation therapy (RT) have an increased risk of hip fractures after treatment. The mechanism of these fractures is unknown; however, femoral fractures have been correlated with cortical bone thinning. The objective of this study was to assess early changes in cortical bone thickness at common sites of femoral fracture in anal cancer patients treated with intensity modulated radiation therapy (IMRT). MATERIALS AND METHODS: RT treatment plans and computed tomography (CT) scans from 23 anal cancer patients who underwent IMRT between November 2012 and December 2014 were retrospectively reviewed. Cortical thickness (Ct.Th) was mapped at homologous vertices within the proximal femur using pre-RT and post-RT (≤4months) CT scans. The bone attenuation measurements were collected at homologous locations within the trabecular bone of the right femoral neck (FN). The percent change in Ct.Th and trabecular bone mineral density (trBMD) were assessed. FN cortical thinning was correlated to RT dose using linear regression. A logistic model for dose dependent cortical thinning was constructed. RESULTS: Twenty-two patients were analyzed. Significant post-treatment cortical thinning was observed in the intertrochanteric crest, subcapital and inferior FN (p<0.05). FN volume receiving ≥40Gy (V40Gy) was a significant predictor of focal cortical thinning ≥30% (p=0.03). A significant decrease in FN trBMD was observed (-6.4% [range -34.4 to 3.3%]; p=0.01). CONCLUSION: Significant early decrease in Ct.Th and trBMD occurs at the FN in patients treated with RT for anal cancer. FN V40Gy was predictive of clinically significant focal FN cortical thinning.
Assuntos
Neoplasias do Ânus/radioterapia , Osso Cortical/patologia , Colo do Fêmur/patologia , Pelve/efeitos da radiação , Adulto , Densidade Óssea , Osso Cortical/efeitos da radiação , Relação Dose-Resposta à Radiação , Feminino , Colo do Fêmur/efeitos da radiação , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , ProbabilidadeRESUMO
We report a single institution series of surgery followed by either early adjuvant or late radiotherapy for atypical meningiomas (AM). AM patients, by WHO 2007 definition, underwent subtotal resection (STR) or gross total resection (GTR). Sixty-three of a total 115 patients then received fractionated or stereotactic radiation treatment, early adjuvant radiotherapy (≤4months after surgery) or late radiotherapy (at the time of recurrence). Kaplan Meier method was used for survival analysis with competing risk analysis used to assess local failure. Overall survival (OS) at 1, 2, and 5years for all patients was 87%, 85%, 66%, respectively. Progression free survival (PFS) at 1, 2, and 5years for all patients was 65%, 30%, and 18%, respectively. OS at 1, 2, and 5years was 75%, 72%, 55% for surgery alone, and 97%, 95%, 75% for surgery+radiotherapy (log-rank p-value=0.0026). PFS at 1, 2, and 5years for patients undergoing surgery without early adjuvant radiotherapy was 64%, 49%, and 27% versus 81%, 73%, and 59% for surgery+early adjuvant radiotherapy (log-rank p-value=0.0026). The cumulative incidence of local failure at 1, 2, and 5years for patients undergoing surgery without early External Beam Radiation Therapy (EBRT) was 18.7%, 35.0%, and 52.9%, respectively, versus 4.2%, 13.3%, and 20.0% for surgery and early EBRT (p-value=0.02). Adjuvant radiotherapy improves OS in patients with AM. Early adjuvant radiotherapy improves PFS, likely due to the improvement in local control seen with early adjuvant EBRT.
Assuntos
Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Recidiva Local de Neoplasia/radioterapia , Radioterapia Adjuvante/métodos , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/cirurgia , Meningioma/mortalidade , Meningioma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Estudos RetrospectivosRESUMO
OBJECTIVE There are a variety of salvage options available for patients with brain metastases who experience local failure after stereotactic radiosurgery (SRS). These options include resection, whole-brain radiation therapy, laser thermoablation, and repeat SRS. There is little data on the safety and efficacy of repeat SRS following local failure of a prior radiosurgical procedure. This study evaluates the clinical outcomes and dosimetric characteristics of patients who experienced tumor recurrence and were subsequently treated with repeat SRS. METHODS Between 2002 and 2015, 32 patients were treated with repeat SRS for local recurrence of ≥ 1 brain metastasis following initial SRS treatment. The Kaplan-Meier method was used to estimate time-to-event outcomes including overall survival (OS), local failure, and radiation necrosis. Cox proportional hazards analysis was performed for predictor variables of interest for each outcome. Composite dose-volume histograms were constructed for each reirradiated lesion, and these were then used to develop a predictive dosimetric model for radiation necrosis. RESULTS Forty-six lesions in 32 patients were re-treated with a second course of SRS after local failure. A median dose of 20 Gy (range 14-22 Gy) was delivered to the tumor margin at the time of repeat SRS. Local control at 1 year was 79% (95% CI 67%-94%). Estimated 1-year OS was 70% (95% CI 55%-88%). Twelve patients had died at the most recent follow-up, with 8/12 patients experiencing neurological death (as described in Patchell et al.). Eleven of 46 (24%) lesions in 11 separate patients treated with repeat SRS were associated with symptomatic radiation necrosis. Freedom from radiation necrosis at 1 year was 71% (95% CI 57%-88%). Analysis of dosimetric data revealed that the volume of a lesion receiving 40 Gy (V40Gy) was the most predictive factor for the development of radiation necrosis (p = 0.003). The following V40Gy thresholds were associated with 10%, 20%, and 50% probabilities of radiation necrosis, respectively: 0.28 cm3 (95% CI 3%-28%), 0.76 cm3 (95% CI 9%-39%), 1.60 cm3 (95% CI 26%-74%). CONCLUSIONS Repeat SRS appears to be an effective salvage option for patients with brain metastases experiencing local failure following initial SRS treatment. This series demonstrates durable local control and, although rates of radiation necrosis are significant, repeat SRS may be indicated for select cases of local disease recurrence. Because the V40Gy is predictive of radiation necrosis, limiting this value during treatment planning may allow for a reduction in radiation necrosis rates.