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Recurrent and anaplastic pleomorphic xanthoastrocytoma (r&aPXA) is a rare primary brain tumor that is challenging to treat. Two-thirds of PXA tumors harbor a BRAF gene mutation. BRAF inhibitors have been shown to improve tumor control. However, resistance to BRAF inhibition develops in most cases. Concurrent therapy with MEK inhibitors may improve tumor control and patient survival. In this study, we identified 5 patients diagnosed with BRAF-mutated PXA who received BRAF and MEK inhibitors over a 10-year interval at our institution. Patient records were evaluated, including treatments, adverse effects (AEs), outcomes, pathology, next-generation sequencing, and MRI. The median age was 22 years (range, 14-66 years), 60% male, and 60% anaplastic PXA. Median overall survival was 72 months (range, 19-112 months); 1 patient died of tumor-related hemorrhage while off therapy, and the other 4 experienced long-term disease control (21, 72, 98, and 112 months, respectively). Dual BRAF/MEK inhibitors were well tolerated, with only grade 1-2 AEs, including rash, neutropenia, fatigue, abdominal discomfort, and diarrhea. No grade 3-5 AEs were detected. A literature review was also performed of patients diagnosed with BRAF-mutated PXA and treated with BRAF and/or MEK inhibitors through August 2021, with a total of 32 cases identified. The median age was 29 years (range, 8-57 years) and the median PFS and OS were 8.5 months (range, 2-35 months) and 35 months (range, 10-80 months), respectively. The most common AEs were grade 1-2 fatigue and skin rash. Results of this case series and literature review indicate that dual-drug therapy with BRAF and MEK inhibitors for r&aPXA with BRAF V600E mutation may delay tumor progression without unexpected AEs.
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Astrocitoma , Neoplasias Encefálicas , Adulto , Femenino , Humanos , Masculino , Adulto Joven , Astrocitoma/tratamiento farmacológico , Astrocitoma/genética , Neoplasias Encefálicas/patología , Fatiga , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/uso terapéutico , Mutación , Recurrencia Local de Neoplasia , Inhibidores de Proteínas Quinasas/efectos adversos , Proteínas Proto-Oncogénicas B-raf/genética , Adolescente , Persona de Mediana Edad , AncianoRESUMEN
INTRODUCTION: Despite aggressive treatment, glioblastoma invariably recurs. The optimal treatment for recurrent glioblastoma (rGBM) is not well defined. Stereotactic radiosurgery (SRS) for rGBM has demonstrated favorable outcomes for selected patients; however, its efficacy in molecular GBM subtypes is unknown. We sought to identify genetic alterations that predict response/outcomes from SRS in rGBM-IDH-wild-type (IDH-WT). METHODS: rGBM-IDH-WT patients undergoing SRS at first recurrence and tested by next-generation sequencing (NGS) were reviewed (2009-2018). Demographic, clinical, and molecular characteristics were evaluated. NGS interrogating 205-genes was performed. Primary outcome was survival from GK-SRS assessed by Kaplan-Meier method and multivariable Cox proportional-hazards. RESULTS: Sixty-three lesions (43-patients) were treated at 1st recurrence. Median age was 61-years. All patients were treated with resection and chemoradiotherapy. Median time from diagnosis to 1st recurrence was 8.7-months. Median cumulative volume was 2.895 cm3 and SRS median marginal dose was 18 Gy (median isodose-54%). Bevacizumab was administered in 81.4% patients. PFS from SRS was 12.9-months. Survival from SRS was 18.2-months. PTEN-mutant patients had a longer PFS (p = 0.049) and survival from SRS (p = 0.013) in multivariable analysis. Although no statistically significant PTEN-mutants patients had higher frequency of radiation necrosis (21.4% vs. 3.4%) and lower in-field recurrence (28.6% vs. 37.9%) compared to PTEN-WT patients. CONCLUSIONS: SRS is a safe and effective treatment option for selected rGBM-IDH-WT patients following first recurrence. rGBM-IDH-WT harboring PTEN-mutation have improved survival with salvage SRS compared to PTEN-WT patients. PTEN may be used as a molecular biomarker to identify a subset of rGBM patients who may benefit the most from SRS.
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Neoplasias Encefálicas/genética , Glioblastoma/genética , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/terapia , Fosfohidrolasa PTEN/genética , Radiocirugia/métodos , Adulto , Anciano , Neoplasias Encefálicas/terapia , Femenino , Glioblastoma/terapia , Humanos , Masculino , Persona de Mediana Edad , Mutación , Estudios Retrospectivos , Terapia Recuperativa/métodosRESUMEN
OBJECTIVE: In this phase II study, we investigate clinical outcomes and tolerability of hypofractionated radiotherapy (HRT) combined with temozolomide (TMZ) to treat elderly patients with glioblastoma (GBM). METHODS: Patients 70 years of age or older with newly diagnosed GBM received HRT to a dose of 34 Gy given in ten fractions over 2 weeks, delivered with concurrent and adjuvant TMZ. RESULTS: In this interim analysis, ten patients were enrolled on trial from 12/1/2015 to 4/5/2017. With a median follow-up of 9 months (range 3-12 months), median progression-free survival (PFS) was 6 months. The median overall survival (OS) has not been reached. Estimated 1-year OS and PFS rates were 53.3 and 44.4%, respectively. All patients completed the full course of RT, with no patients developing grade 3 or higher adverse events from treatment. CONCLUSIONS: The preliminary results of our phase II trial suggest HRT delivered over 2 weeks with concurrent and adjuvant TMZ is well tolerated in elderly patients with GBM without compromising clinical outcomes.
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Antineoplásicos Alquilantes/efectos adversos , Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Dacarbazina/análogos & derivados , Glioblastoma/tratamiento farmacológico , Glioblastoma/radioterapia , Hipofraccionamiento de la Dosis de Radiación , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/mortalidad , Dacarbazina/efectos adversos , Dacarbazina/uso terapéutico , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Glioblastoma/mortalidad , Humanos , Masculino , Calidad de Vida , Encuestas y Cuestionarios , TemozolomidaRESUMEN
We sought to determine the impact of time to initiation (TTI) of post-operative radiosurgery on clinical outcomes for patients with resected brain metastases and to identify predictors associated with TTI. All patients with resected brain metastases treated with postoperative SRS or fractionated stereotactic radiation therapy (fSRT) from 2012 to 2016 at a single institution were reviewed. TTI was defined as the interval from resection to first day of radiosurgery. Receiver operating characteristic (ROC) curves were used to identify an optimal threshold for TTI with respect to local failure (LF). Survival outcomes were estimated using the Kaplan-Meier method and analyzed using the log-rank test and Cox proportional hazards models. Logistic regression models were used to identify factors associated with ROC-determined TTI covariates. A total of 79 resected lesions from 73 patients were evaluated. An ROC curve of LF and TTI identified an optimal threshold for TTI of 30.5 days, with an area under the curve of 0.637. TTI > 30 days was associated with an increased hazard of LF (HR 4.525, CI 1.239-16.527) but was not significantly associated with survival (HR 1.002, CI 0.547-1.823) or distant brain failure (DBF, HR 1.943, CI 0.989-3.816). Fifteen patients (20.5%) required post-operative inpatient rehabilitation. Post-operative rehabilitation was associated with TTI > 30 days (OR 1.48, CI 1.142-1.922). In our study of resected brain metastases, longer time to initiation of post-operative radiosurgery was associated with increased local failure. Ideally, post-op SRS should be initiated within 30 days of resection if feasible.
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Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/terapia , Procedimientos Neuroquirúrgicos , Radiocirugia , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/mortalidad , Terapia Combinada/métodos , Fraccionamiento de la Dosis de Radiación , Humanos , Persona de Mediana Edad , Periodo Posoperatorio , Pronóstico , Radiocirugia/métodos , Tiempo de TratamientoRESUMEN
BACKGROUND: The objectives of this study were to characterize patterns of care and to identify predictors for adjuvant therapy in elderly patients with glioblastoma in the modern era. METHODS: The National Cancer Data Base was queried for patients aged 70 years and older with glioblastoma diagnosed from January 1, 2004 through December 31, 2012. Multinomial logistic regression was used to identify predictors for receiving adjuvant therapy. Survival outcomes were estimated using the Kaplan-Meier method and were analyzed using Cox regression models and the log-rank test. RESULTS: In total, 14,886 patients were identified. Of these, 8214 patients (55.2%) received combined-modality therapy with chemotherapy and radiation (CRT), 3955 (26.6%) received no adjuvant therapy, 2065 (13.9%) received radiation therapy (RT) alone, and 652 (4.4%) received chemotherapy (CT) alone after undergoing resection. The receipt of CRT increased in frequency over the study interval, from 40.3% in 2004 to 59.8% in 2012. Younger patients (ages 70-75 years) were more likely to receive CRT than no adjuvant therapy (P < .0001 for all other age groups) or adjuvant RT alone (P < .0001 for all other age groups). Combined-modality therapy with adjuvant CRT produced improved survival outcomes, and the highest median overall survival was 9.2 months. CONCLUSIONS: In this analysis of elderly patients who had glioblastoma diagnosed from 2004 through 2012, a significant increase in the receipt of combined-modality therapy was observed. Combined-modality treatment produces improved survival outcomes and should be considered as adjuvant treatment for carefully selected elderly patients. Cancer 2017;123:3277-84. © 2017 American Cancer Society.
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Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/terapia , Glioblastoma/mortalidad , Glioblastoma/terapia , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/patología , Quimioradioterapia/métodos , Estudios de Cohortes , Terapia Combinada , Bases de Datos Factuales , Supervivencia sin Enfermedad , Femenino , Evaluación Geriátrica , Glioblastoma/patología , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Análisis Multivariante , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Procedimientos Neuroquirúrgicos/métodos , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Estados UnidosRESUMEN
PURPOSE: To report outcomes for patients with cervical lymph node metastases from an unknown primary site of the head and neck treated with either non-operative therapy or neck dissection followed by adjuvant therapy. MATERIALS AND METHODS: All patients with squamous cell carcinoma of an unknown primary site of the head or neck seen between 2003 and 2013 were reviewed. The Kaplan-Meier method was used to estimate overall survival, local recurrence free survival, loco-regional recurrence free survival, and progression free survival. The log-rank test and proportional hazards regression were used to analyze factors influencing outcomes. RESULTS: Of 2258 patients with a new diagnosis of head and neck cancer, no primary site was identified in 66 patients. Twenty-nine patients were treated with definitive non-operative therapy (15 with chemoradiation and 14 with radiation alone). Thirty-seven patients received an upfront neck dissection followed by adjuvant radiation or chemoradiation. Three-year loco-regional recurrence free survival, progression free survival, and overall survival were 55.9%, 55.4%, and 69.4% respectively. Patients treated with preoperative neck dissection had improved local recurrence free survival (96.7% vs 54.1%, p=0.003) and loco-regional recurrence free survival (82.2% vs 46.4%, p=0.068) compared to patients treated with definitive chemoradiation with no difference in overall survival (p=0.641). CONCLUSIONS: Neck dissection improved local and regional control but not overall survival in patients with unknown primary squamous cell carcinoma of the head and neck over non-operative therapy alone.
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Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeza y Cuello/secundario , Neoplasias de Cabeza y Cuello/terapia , Disección del Cuello , Neoplasias Primarias Desconocidas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Quimioradioterapia , Supervivencia sin Enfermedad , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias Primarias Desconocidas/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
Stereotactic ablative radiotherapy delivers a high dose of radiation to a small volume over several fractions. Although most commonly used as a treatment alternative to surgery in adult patients with primary lung cancer, its use has now been reported in children with metastatic disease to the lungs. We present the case of a child treated with stereotactic ablative radiotherapy to pulmonary metastases in preparation for a salvage stem cell transplant. The patient was treated to a dominant pulmonary nodule and successfully received his stem cell transplant, however he developed clinical and radiographic findings consistent with pneumonitis several months after treatment.
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Neoplasias Óseas/patología , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/secundario , Radiocirugia , Sarcoma de Ewing/radioterapia , Adolescente , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Tomografía Computarizada por Rayos XRESUMEN
While typically used for treating small intact brain metastases, an increasing body of literature examining tumor bed directed stereotactic radiosurgery (SRS) is emerging. There are now over 1000 published cases treated with this approach, and the first prospective trial was recently published. The ideal sequencing of tumor bed SRS is unclear. Current approaches include, a neoadjuvant treatment before resection, alone as an adjuvant after resection, and following surgery combined with whole brain radiotherapy either as an adjuvant or salvage treatment. Based on available evidence, adjuvant stereotactic radiosurgery improves local control following surgery, reduces the number of patients who require whole brain radiotherapy, and is well tolerated. While results from published series vary, heterogeneity in both patient populations and methods of reporting results make comparisons difficult. Additional prospective data, including randomized trials are needed to confirm equivalent outcomes to the current standard of care. We review the current literature, identify areas of ongoing contention, and highlight ongoing studies.
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Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/cirugía , Radiocirugia , HumanosRESUMEN
The Von-Hippel-Lindau (VHL) gene, acting as a tumor suppressor, plays a crucial role in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). Approximately 90% of individuals with advanced ccRCC exhibit somatic mutations in the VHL gene. Belzutifan, orally administered small-molecule inhibitor of hypoxia-induced factor-2α, has demonstrated promising efficacy in solid tumors associated with germline loss-of-function mutations in VHL, including ccRCC. However, its impact on cases with somatic or sporadic VHL mutations remains unclear. Here, we present 2 cases where belzutifan monotherapy was employed in patients with advanced ccRCC and somatic loss-of-function mutations in VHL. Both patients exhibited a swift and sustained response, underscoring the potential role of belzutifan as a viable option in second or subsequent lines of therapy for individuals with somatic VHL mutations. Despite both patients experiencing a pulmonary crisis with respiratory compromise, their rapid response to belzutifan further emphasizes its potential utility in cases involving pulmonary or visceral crises. This report contributes valuable insights into the treatment landscape for advanced ccRCC with somatic VHL mutations.
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Carcinoma de Células Renales , Carcinoma , Indenos , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , MutaciónRESUMEN
PURPOSE: Diffusion tensor imaging for evaluation of white matter tracts is used with magnetic resonance spectroscopy (MRS) to improve management of diffuse intrinsic pontine glioma (DIPG). Changes in the apparent diffusion coefficient (ADC), fractional anisotropy (FA), and tumor metabolite ratios have been reported after initial radiation for DIPG, but these markers have not been studied sequentially in patients undergoing reirradiation for progressive DIPG. Here, we report a case series of 4 patients who received reirradiation for progressive DIPG on a prospective clinical trial in which we evaluated quantitative changes in FA, ADC, and tumor metabolites and qualitative changes in white matter tracts. METHODS AND MATERIALS: The median reirradiation dose was 25.2 Gy (24-30.8 Gy). Fiber tracking was performed using standard tractography analysis. The FA and ADC values for the corticospinal and medial lemniscus tracts were calculated before and after reirradiation. Multivoxel MRS was performed. Findings were correlated with clinical features and conventional MRI of tumors. RESULTS: All patients had an initial response to reirradiation as shown by a decrease in tumor size. In general, FA increased with disease response and decreased with progression, whereas ADC decreased with disease response and increased with progression. At second progression, the FA fold change relative to values during disease response decreased in both patients with available imaging at second progression. Visualization of tracts demonstrated robust reconstitution of previously disrupted paths during tumor response; conversely, there was increased fiber tract disruption and infiltration during tumor progression. The MRS analysis revealed a decrease in choline:creatinine and choline:N-acetylaspartate ratios during tumor response and increase during progression. CONCLUSIONS: Distinct changes in white matter tracts and tumor metabolism were observed in patients with DIPG undergoing reirradiation on a prospective clinical trial. Changes related to tumor response and progression were observed after 24 to 30.8 Gy reirradiation.
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BACKGROUND: Multisession staged stereotactic radiosurgery (SRS) represents an alternative approach for management of large brain metastases (LBMs), with potential advantages over fractionated SRS. This study investigated clinical efficacy and safety of 2-stage stereotactic radiosurgery (2-SSRS) in patients with LBMs. METHODS: Patients with LBMs treated with 2-SSRS between 2014 and 2020 were evaluated. Demographic, clinical, and radiologic data were obtained. Volumetric measurements at first SRS session, second SRS session, and follow-up imaging studies were obtained. Characteristics that might predict response to 2-SSRS were evaluated through Fisher exact or Mann-Whitney U test. RESULTS: The study included 24 patients with 26 LBMs. Median (range) marginal doses for first and second SRS sessions were 15 Gy (14-18 Gy) and 15 Gy (12-16 Gy), respectively. Median (range) tumor volumes at first SRS session, second SRS session, and 3-month follow-up were 8.1 cm3 (1.5-28.5 cm3), 3.3 cm3 (0.8-26.1 cm3), and 2.2 cm3 (0.2-10.1 cm3), respectively. Of 26 lesions, 24 (92%) demonstrated early local control following the first SRS session, with 17 lesions (71%) demonstrating a decrease of ≥30% in T1 postcontrast MRI volume before the second SRS session and 3 lesions (12%) remaining stable. Eventually, 4 lesions showed disease progression after 2-SSRS. The median time to local progression was not reached; the median time to intracranial progression was 9.1 months. CONCLUSIONS: Our study supports the effectiveness and safety of 2-SSRS as a treatment modality for patients with LBMs, especially in poor surgical candidates. The local failure rate and low occurrence of adverse effects are comparable to other staged radiosurgery studies.
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Neoplasias Encefálicas , Neoplasias Primarias Secundarias , Radiocirugia , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Humanos , Cinética , FísicaRESUMEN
BACKGROUND: Though conventionally fractionated chemoradiation (CRT) is well tolerated by selected patients with newly diagnosed glioblastoma (GBM), adverse health-related and nonhealth-related factors can lead to unplanned interruptions in treatment. The effects of prolonged time to completion (TTC) of radiation therapy (RT) on overall survival (OS) for these patients are unclear. METHODS: The National Cancer Database (NCDB) was queried for all adult patients with newly diagnosed GBM undergoing surgical resection followed by adjuvant CRT with conventionally fractionated RT (6000-6600 cGy in 30-33 fractions) from 2005 to 2012. TTC was defined as the interval from first to last fraction of RT. Recursive partitioning analysis (RPA) was used to determine a threshold for TTC of adjuvant RT. Cox proportional hazards modeling was used to identify covariates associated with OS. RESULTS: A total of 13489 patients were included in our cohort. Patients who completed adjuvant RT within the RPA-defined threshold of 46 days from initiation of RT (median OS: 14.0 months, 95% confidence interval (CI) 13.7 to 14.3 months) had significantly improved OS compared to patients with TTC of 47 days or greater (median OS: 12.0 months, 95% CI 11.4 to 12.6 months, P < .001). Delays in completing adjuvant RT were relatively common, with 15.0% of patients in our cohort having a TTC of RT of 47 days or greater. CONCLUSIONS: Delays in completing adjuvant RT were associated with a worse survival outcome. Any unnecessary delays in completing adjuvant RT should be minimized while ensuring the safe delivery of therapy.
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The optimal timing of adjuvant chemoradiation after surgical resection of glioblastoma remains unknown. The National Cancer Database was queried for all patients diagnosed with glioblastoma from 2004 to 2012 who underwent surgical resection followed by adjuvant chemoradiation. Cox proportional hazards modeling was used to determine factors influencing survival. Optimal thresholds for time to initiation (TTI) of adjuvant therapy were determined using recursive partitioning analysis (RPA). A total of 16,335 patients were included. The RPA model identified an optimal threshold of 61â¯days to initiation of adjuvant therapy which was confirmed with randomly selected training and validation sets using conditional inference trees repeated 1000 times for robustness. Compared to patients who initiated adjuvant therapy within 61â¯days (median overall survival: 14.1â¯months, 95% CI 13.8-14.3â¯months), patients who initiated adjuvant therapy after day 61 (MOS: 12.0, CI: 10.7-12.9) had higher risk of death (pâ¯<â¯0.0001). For patients with glioblastoma, large increases in time to the initiation of adjuvant therapy leads to inferior survival with a threshold of 61â¯days or less following surgical resection.
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Neoplasias Encefálicas/terapia , Quimioradioterapia Adyuvante/métodos , Glioblastoma/terapia , Adulto , Anciano , Neoplasias Encefálicas/epidemiología , Quimioradioterapia Adyuvante/mortalidad , Bases de Datos Factuales/estadística & datos numéricos , Esquema de Medicación , Femenino , Glioblastoma/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Análisis de SupervivenciaRESUMEN
PURPOSE: To identify an optimal dose for reirradiation (reRT) of diffuse intrinsic pontine glioma. METHODS AND MATERIALS: ReRT dose levels were selected using an adaptive utility-based dose-finding method. The coprimary endpoints were toxicity (mild, moderate, high, or severe) and efficacy, evaluated 1 month after reRT. Efficacy was defined as improvements in imaging, clinical status, and quality of life. Secondary endpoints were progression-free and overall survival. Utility of each dose level was calculated based on a combined toxicity/efficacy score, ranging from 0 for (severe toxicity, no efficacy) to 100 for (mild toxicity, all 3 efficacy improvements). RESULTS: Twelve patients completed reRT at 3 dose levels: 24 Gy in 12 fractions (6 patients), 26.4 Gy in 12 fractions (4 patients), and 30.8 Gy in 14 fractions (2 patients). One patient treated at dose level 3 developed a grade 3 acute toxicity. Five of the 6 patients receiving 24 Gy demonstrated improvement in 2 of 3 efficacy domains, and the sixth demonstrated improvement in all efficacy domains. Of 4 patients receiving 26.4 Gy, 1 demonstrated no improvement, and 1 patient each demonstrated improvement in 1, 2, and 3 efficacy domains. Of 2 patients receiving 30.8 Gy, 1 demonstrated improvement in 3 efficacy domains, and 1 did not complete the quality of life and was not assessed. Mean utilities were 88 for dose level 1, 76 for dose level 2, and 25 for dose level 3. For all patients, the median overall survival was 19.5 months from initial diagnosis (95% confidence interval, 15.6-21.1 months), and the median progression-free survival was 4.5 months from the start of reRT (95% confidence interval, 2.7-6.2 months). CONCLUSIONS: ReRT can safely be delivered for progressive diffuse intrinsic pontine glioma. Clinical improvement was seen in almost all patients. Utility analysis suggests that a regimen of 24 Gy in 12 fractions is preferred.
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Neoplasias del Tronco Encefálico/radioterapia , Glioma/radioterapia , Reirradiación/métodos , Adolescente , Adulto , Neoplasias del Tronco Encefálico/mortalidad , Neoplasias del Tronco Encefálico/patología , Niño , Preescolar , Fraccionamiento de la Dosis de Radiación , Femenino , Glioma/mortalidad , Glioma/patología , Humanos , Masculino , Supervivencia sin Progresión , Estudios Prospectivos , Calidad de Vida , Traumatismos por Radiación/etiología , Reirradiación/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The effect of increasing time to definitive radiotherapy (RT) for patients with oropharyngeal squamous cell carcinoma (SCC) is unknown. METHODS: Nodal tumor volumes at staging and simulation were compared for patients with oropharyngeal SCC. Time from staging to initiation of RT was tabulated. The primary endpoint of interest was nodal progression at simulation. RESULTS: Increasing time to simulation was associated with nodal progression in 144 patients (r = 0.474; P < .001). Patients with human papillomavirus (HPV)-associated oropharyngeal SCC were more likely to have nodal progression (50% vs 26%; P = .008). A threshold of 32 days was associated (sensitivity 77.9% and specificity 60.2%) with nodal progression (P < .001). Increasing time from staging to treatment initiation was associated with a greater risk of distant failure (hazard ratio [HR] 4.157; 95% confidence interval [CI] 1.170-14.764) but not progression-free survival (PFS; P = .179) or overall survival (OS; P = .474). CONCLUSION: Increasing time before RT for patients with oropharyngeal SCC is associated with nodal progression and increased hazard of distant failure, although not PFS or OS in our population.
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Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/radioterapia , Infecciones por Papillomavirus/patología , Fumar/efectos adversos , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/virología , Causas de Muerte , Estudios de Cohortes , Bases de Datos Factuales , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Laringectomía/métodos , Laringectomía/mortalidad , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Neoplasias Orofaríngeas/mortalidad , Neoplasias Orofaríngeas/virología , Infecciones por Papillomavirus/epidemiología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Fumar/epidemiología , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the efficacy of immune checkpoint therapy (ICT) administered with stereotactic radiosurgery (SRS) and determine the effects of relative treatment timing on lesion response. METHODS: A prospective institutional database of all patients with intact brain metastases treated with SRS from 2008 to 2015 was reviewed for patients diagnosed with malignant melanoma. Lesion response was determined using a modified RECIST v1.1 criteria. Patients were grouped according to if they received ICT and the timing of ICT relative to SRS. Cox regression was used to identify predictors of lesion failure (LF) and distant brain failure (DBF). The Wilcoxon rank-sum test was used to compare median lesion regression after SRS between treatment groups. RESULTS: Fifty-one patients with 167 metastases were evaluated. Eighteen patients (59 lesions) were treated with peri-SRS ICT with anticytotoxic T-lymphocyte-associated protein 4 or antiprogrammed cell death protein 1 therapy. Peri-SRS ICT was a significant favorable predictor for reduced hazard of LF (hazard ratio, 0.131; confidence interval, 0.028-0.610). Concurrent ICT given with SRS (hazard ratio, 0.364; confidence interval, 0.161-0.825) significantly predicted freedom from DBF. When quantitative lesion response was examined, peri-SRS ICT resulted in a significantly greater median percent lesion regression than did SRS alone at 1.5 (-30.7% vs. -14.6%; P = 0.018), 4 (-42.3% vs. -18.8%; P = 0.031), and 5 months after SRS (-52.01 vs. -14.9%; P = 0.002). CONCLUSIONS: ICT combined with SRS was associated with greater lesion regression of melanoma brain metastases and decreased LF. When given concurrently, combined SRS and ICT may result in improved freedom from DBF.
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Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/terapia , Inmunoterapia , Melanoma/secundario , Melanoma/terapia , Radiocirugia , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/diagnóstico por imagen , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/inmunología , Terapia Combinada , Bases de Datos Factuales , Humanos , Estimación de Kaplan-Meier , Melanoma/diagnóstico por imagen , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Purpose/Objective(s): To establish a dose-volume response relationship for brain metastases treated with single-fraction robotic stereotactic radiosurgery and identify predictors of local control. MATERIALS/METHODS: We reviewed a prospective institutional database of all patients treated for intact brain metastases with stereotactic radiosurgery alone using the CyberKnife robotic radiosurgery system from 2012 to 2015. Tumor response was determined based on Response Evaluation Criteria In Solid Tumors version 1.1. Survival was estimated using the Kaplan-Meier method. Logistic regression modeling was used to identify predictors of outcome and establish a dose-volume response relationship. Receiver operating characteristic curves were constructed to evaluate the predictive capability of the relationship. RESULTS: There were 357 metastases evaluated in 111 patients with a median diameter of 8.14 mm (2.00-40.77 mm). At 6 and 12 months, local control was 86.9% and 82.2%, respectively. For lesions of similar volumes, higher maximum dose, mean dose, and minimum dose (all P values <.05) predicted for better local control. Tumor volume and diameter were strongly correlated, and a dose-volume response relationship was constructed using mean dose per lesion diameter (Gy/mm) that was predictive of local control (odds ratio: 1.34, 95% confidence interval: 1.06-1.70). Area under the receiver operating characteristic curve for local control and mean dose by volume was 0.6199 with a threshold of 2.05 Gy/mm (local failure 7.6% above and 17.3% below 2.05 Gy/mm). CONCLUSION: A dose-volume response relationship exists for brain metastases treated with robotic stereotactic radiosurgery. Mean dose per volume is strongly predictive of local control and can be potentially useful during stereotactic radiosurgery plan evaluation while respecting previously established dose constraints.
Asunto(s)
Neoplasias Encefálicas/radioterapia , Radiocirugia/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/secundario , Supervivencia sin Enfermedad , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Radiocirugia/efectos adversos , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Carga TumoralRESUMEN
OBJECTIVES: To compare the outcomes and toxicity of high-dose cisplatin (HDC) versus weekly cisplatin (WC) definitive chemoradiotherapy (CRT) for patients with human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (SCCOPx). METHODS: All patients with p16 positive SCCOPx treated with definitive CRT with cisplatin between 2010 and 2014 at a single institution were retrospectively reviewed. CTCAE v 4.03 toxicity criteria were used. The Kaplan-Meier method was used to estimate event-free survival (EFS) and the overall survival (OS). RESULTS: Of the 55 patients included, 22 were patients treated with HDC at dose of 100mg/m2 on days 1 and 22; and the remaining 33 patients were treated with WC at 40mg/m2. Both cohorts received a median total dose of cisplatin of 200mg/m2. At median follow-up of 31months, there was one local failure and no distant failures in the HDC cohort. In the WC group, there were 6 total failures (2 local, 4 distant). Estimated 2-year EFS was better in HDC cohort as compared to WC (96% vs. 75%; p=0.04). There was no significant difference in 2-year OS (95% vs. 94%; p=0.40). Weight loss, gastric tube dependence at six months, acute renal injury and grade 3 or 4 hematological toxicity were all similar between both groups. CONCLUSIONS: HPV-related SCCOPx treated with definitive CRT with either HDC or WC had similar toxicity profile. HDC had better EFS when compared with WC and this seems to be driven by increased distant failure rates, although the OS was similar.
Asunto(s)
Alphapapillomavirus/patogenicidad , Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Cisplatino/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias Orofaríngeas/tratamiento farmacológico , Adulto , Anciano , Carcinoma de Células Escamosas/virología , Relación Dosis-Respuesta a Droga , Femenino , Neoplasias de Cabeza y Cuello/virología , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/virología , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
BACKGROUND: The role of adjuvant stereotactic radiosurgery (SRS) and fractionated radiotherapy (XRT) are unknown in patients with resected meningiomas. OBJECTIVE: To identify patterns of care and outcomes of adjuvant radiotherapy for meningiomas in the Linked Surveillance, Epidemiology, and End Results (SEER) Medicare data. METHODS: A total of 1,964 patients older than 66 years included in the SEER-Medicare data, who were diagnosed with meningioma, and underwent craniotomy were included for analysis. RESULTS: Patients were less likely to receive adjuvant therapy if they were older than 75 (OR 0.730, 95% CI 0.548-0.973), female sex (OR 0.731, 95% CI 0.547-0.978), or unmarried (OR 0.692, 95% CI 0.515-0.929). Patients were more likely to receive adjuvant treatment for Grade II/III tumors (OR 5.586, 95% CI 2.135-13.589), tumors over 5 cm (OR 1.850, 95% CI 1.332-2.567), or partial resection (OR 3.230, 95% CI 2.327-4.484). Yearly between 2000 and 2009, 10.65 - 19.77% of patients received adjuvant therapy. Although no survival benefit was seen with the addition of adjuvant therapy (p = 0.1236), the subgroup of patients receiving SRS had a decreased risk of death compared to those receiving surgery alone (aHR 0.544, 95% CI 0.318 - 0.929). CONCLUSION: Utilization of adjuvant XRT and SRS remained stable between 2000 and 2010. Male sex, young age, marriage, partial resection, Grade II/III tumors, and large tumors predicted the use of adjuvant therapy. For all patients, SRS decreased the risk of death compared to craniotomy alone.
RESUMEN
STUDY OBJECTIVE: To determine the optimal epidural analgesia for patients receiving interstitial brachytherapy (ISBT) for gynecologic cancers. DESIGN: Retrospective analysis. SETTING: Operating room and hospital ward. PATIENTS: Seventy-three patients diagnosed as having gynecologic cancer and undergoing ISBT. INTERVENTIONS: Twelve patients received ropivacaine alone, 14 patients received ropivacaine with fentanyl, and 45 patients received ropivacaine with hydromorphone by epidural infusion. MEASUREMENTS: Numeric Rating Scale pain scores, amounts of nonnarcotic and narcotic pain medications used in intravenous morphine equivalents (IVMEs), and amount of antiemetic or antipruritic medications used. MAIN RESULTS: Patients receiving ropivacaine alone had higher pain scores the morning of day 2 (4.2 vs 1.71 vs 0.6, P=.001), the afternoon of day 2 (4.9 vs 2.5 vs 1.7, P=.005), and the night of day 2 (2.4 vs 2.0 vs 0.6, P<.001). Patients receiving opioids in their epidural had lower pain scores on the night of placement (P=.050), the morning of day 2 (P<.001), the afternoon of day 2 (P=.002), and the night of day 2 (P<.001). Patients receiving ropivacaine alone used more oral narcotics than did those receiving ropivacaine with fentanyl or ropivacaine with hydromorphone on day 3 (5.9 vs 3.8 vs 2.8mg IVME) and received more intravenous opioids day 1 (5.8 vs 0.0 vs 0.7mg IVME, P=.004) and day 2 (20.6 vs 4.8 vs 1.0mg IVME, P=.042). There were no differences in antiemetic or diphenhydramine usage at any time point. No epidural complications occurred. CONCLUSIONS: For patients receiving ISBT for gynecologic cancer, epidural analgesia provides safe and effective pain control. Combined modality epidural analgesia improves pain control and lessens oral and intravenous opioid requirements without increased risk of adverse effects compared with epidural analgesia with local anesthetic alone.