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1.
Nat Med ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39169220

RESUMO

Treatment of the tumor and dural margin with surgery and sometimes radiation are cornerstones of therapy for meningioma. Molecular classifications have provided insights into the biology of disease; however, response to treatment remains heterogeneous. In this study, we used retrospective data on 2,824 meningiomas, including molecular data on 1,686 tumors and 100 prospective meningiomas, from the RTOG-0539 phase 2 trial to define molecular biomarkers of treatment response. Using propensity score matching, we found that gross tumor resection was associated with longer progression-free survival (PFS) across all molecular groups and longer overall survival in proliferative meningiomas. Dural margin treatment (Simpson grade 1/2) prolonged PFS compared to no treatment (Simpson grade 3). Molecular group classification predicted response to radiotherapy, including in the RTOG-0539 cohort. We subsequently developed a molecular model to predict response to radiotherapy that discriminates outcome better than standard-of-care classification. This study highlights the potential for molecular profiling to refine surgical and radiotherapy decision-making.

2.
Neuro Oncol ; 25(7): 1323-1330, 2023 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-36734195

RESUMO

BACKGROUND: Brain metastases are the most common intracranial tumors in adults and are associated with significant morbidity and mortality. Whole-brain radiotherapy (WBRT) is used frequently in patients for palliation, but can result in neurocognitive deficits. While dose-dependent injury to individual areas such as the hippocampus has been demonstrated, global structural shape changes after WBRT remain to be studied. METHODS: We studied healthy controls and patients with brain metastases and examined MRI brain anatomic surface data before and after WBRT. We implemented a validated graph convolutional neural network model to estimate patient's "brain age". We further developed a mixed-effects linear model to compare the estimated age of the whole brain and substructures before and after WBRT. RESULTS: 4220 subjects were analyzed (4148 healthy controls and 72 patients). The median radiation dose was 30 Gy (range 25-37.5 Gy). The whole brain and substructures underwent structural change resembling rapid aging in radiated patients compared to healthy controls; the whole brain "aged" 9.32 times faster, the cortex 8.05 times faster, the subcortical structures 12.57 times faster, and the hippocampus 10.14 times faster. In a subset analysis, the hippocampus "aged" 8.88 times faster in patients after conventional WBRT versus after hippocampal avoidance (HA)-WBRT. CONCLUSIONS: Our findings suggest that WBRT causes the brain and its substructures to undergo structural changes at a pace up to 13x of the normal aging pace, where hippocampal avoidance offers focal structural protection. Correlating these structural imaging changes with neurocognitive outcomes following WBRT or HA-WBRT would benefit from future analysis.


Assuntos
Neoplasias Encefálicas , Aprendizado Profundo , Radioterapia de Intensidade Modulada , Adulto , Humanos , Radioterapia de Intensidade Modulada/efeitos adversos , Irradiação Craniana/efeitos adversos , Irradiação Craniana/métodos , Encéfalo , Neoplasias Encefálicas/patologia , Hipocampo/patologia , Envelhecimento , Dosagem Radioterapêutica
3.
Phys Imaging Radiat Oncol ; 24: 71-75, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36217428

RESUMO

This study aimed to assess the incidental radiation exposure of the hippocampus (HC) in locoregionally-advanced oropharyngeal cancer patients undergoing volumetric modulated arc therapy and the feasibility of HC-sparing plan optimization. The initial plans were generated without dose-volume constraints to the HC and were compared with the HC-sparing plans. The incidental Dmean_median doses to the bilateral, ipsilateral and contralateral HC were 2.9, 3.1, and 2.5 Gy in the initial plans and 1.4, 1.6, and 1.3 Gy with HC-sparing. It was feasible to reduce the HC dose with HC-sparing plan optimization without compromising target coverage and/or dose constraints to other OARs.

4.
World Neurosurg ; 165: e380-e385, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35724885

RESUMO

OBJECTIVE: Gamma Knife (GK) stereotactic radiosurgery (SRS) is increasingly used as an initial treatment for patients with 10 or more brain metastases. However, the clinical and dosimetric consequences of this practice are not well established. METHODS: We performed a single-institution, retrospective analysis of 30 patients who received Gamma Knife SRS for 10 or more brain metastases in 1 session. We utilized MIM Software to contour the whole brain and accumulated the doses from all treated lesions to determine the mean dose delivered to the whole brain. Patient outcomes were determined from chart review. RESULTS: Our cohort had a median number of 13 treated lesions (range 10-26 lesions) for a total of 427 treated lesions. The mean dose to the whole brain was determined to be 1.8 ± 0.91 Gy (range 0.70-3.8 Gy). The mean dose to the whole brain did not correlate with the number of treated lesions (Pearson r = 0.23, P = 0.21), but was closely associated with tumor volume (Pearson r = 0.95, P < 0.0001). There were no significant correlations between overall survival and number of lesions or aggregate tumor volume. Fourteen patients (47%) underwent additional SRS sessions and 6 patients (20%) underwent whole-brain radiotherapy with a median of 6.6 months (range 3.0-50 months) after SRS. Two patients (6.6%) developed grade 2 radionecrosis following SRS beyond earlier whole-brain radiotherapy. CONCLUSION: The mean dose to the whole brain in patients treated with Gamma Knife SRS for 10 or more brain metastases remained low with an acceptable rate of radionecrosis. This strategy allowed the majority of patients to avoid subsequent whole-brain radiotherapy.


Assuntos
Neoplasias Encefálicas , Lesões por Radiação , Radiocirurgia , Encéfalo , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Humanos , Lesões por Radiação/etiologia , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
5.
J Neurooncol ; 158(3): 331-339, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35525907

RESUMO

PURPOSE: We investigated the prognostic significance of tumor-associated white matter (TA-WM) tracts in glioblastoma (GBM) using magnetic resonance-diffusion tensor imaging (MR-DTI). We hypothesized that (1) TA-WM tracts harbor microscopic disease not targeted through surgery or radiotherapy (RT), and (2) the greater the extent of TA-WM involvement, the worse the survival outcomes. METHODS: We studied a retrospective cohort of 76 GBM patients. TA-WM tracts were identified by MR-DTI fractional anisotropy (FA) maps. For each patient, 22 TA-WM tracts were analyzed and each tract was graded 1-3 based on FA. A TA-WM score (TA-WMS) was computed based on number of involved tracts and corresponding FA grade of involvement. Kaplan-Meier statistics were utilized to determine survival outcomes, log-rank test was used to compare survival between groups, and Cox regression was utilized to determine prognostic variables. RESULTS: For the MGMT-unmethylated cohort, there was a decrease in OS for increasing TA-WMS (median OS 16.5 months for TA-WMS 0-4; 13.6 months for TA-WMS 5-8; 7.3 months for TA-WMS > 9; p = 0.0002). This trend was not observed in the MGMT-methylated cohort. For MGMT-unmethylated patients with TA-WMS > 6 and involvement of tracts passing through brainstem or contralateral hemisphere, median OS was 8.3 months versus median OS 14.1 months with TA-WMS > 6 but not involving aforementioned critical tracts (p = 0.003 log-rank test). For MGMT-unmethylated patients, TA-WMS was predictive of overall survival in multivariate analysis (HR = 1.14, 95% CI 1.03-1.27, p = 0.012) while age, gender, and largest tumor dimension were non-significant. CONCLUSION: Increased TA-WMS and involvement of critical tracts are associated with decreased overall survival in MGMT-unmethylated GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Substância Branca , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Metilação de DNA , Metilases de Modificação do DNA/genética , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Imagem de Tensor de Difusão , Glioblastoma/diagnóstico por imagem , Glioblastoma/genética , Glioblastoma/terapia , Humanos , Prognóstico , Regiões Promotoras Genéticas , Estudos Retrospectivos , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Substância Branca/patologia
6.
J Neurooncol ; 155(3): 297-306, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34689306

RESUMO

PURPOSE: Survival is dismal for bevacizumab refractory high-grade glioma patients. We prospectively investigated the efficacy of re-irradiation, bevacizumab, and temozolomide in bevacizumab-naïve and bevacizumab-exposed recurrent high-grade glioma, without volume limitations, in a single arm trial. METHODS: Recurrent high-grade glioma patients were stratified based on WHO grade (4 vs. < 4) and prior exposure to bevacizumab (yes vs. no). Eligible patients received radiation using a simultaneous integrated boost technique (55 Gy to enhancing disease, 45 Gy to non-enhancing disease in 25 fractions) with bevacizumab 10 mg/kg every 2 weeks IV and temozolomide 75 mg/m2 daily followed by maintenance bevacizumab 10 mg/kg every 2 weeks and temozolomide 50 mg/m2 daily for 6 weeks then a 2 week holiday until progression. Primary endpoint was overall survival. Quality of life was studied using FACT-Br and FACT-fatigue scales. RESULTS: Fifty-four patients were enrolled. The majority (n = 36, 67%) were bevacizumab pre-exposed GBM. Median OS for all patients was 8.5 months and 7.9 months for the bevacizumab pre-exposed GBM group. Patients ≥ 36 months from initial radiation had a median OS of 13.3 months compared to 7.5 months for those irradiated < 36 months earlier (p < 0.01). FACT-Br and FACT-Fatigue scores initially declined during radiation but returned to pretreatment baseline. Treatment was well tolerated with 5 patients experiencing > grade 3 lymphopenia and 2 with > grade 3 thrombocytopenia. No radiographic or clinical radiation necrosis occurred. CONCLUSIONS: Re-irradiation with bevacizumab and temozolomide is a safe and feasible salvage treatment for patients with large volume bevacizumab-refractory high-grade glioma. Patients further from their initial radiotherapy may derive greater benefit with this regimen.


Assuntos
Neoplasias Encefálicas , Quimiorradioterapia , Glioma , Reirradiação , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Fadiga , Glioma/tratamento farmacológico , Glioma/radioterapia , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia , Estudos Prospectivos , Qualidade de Vida , Temozolomida/uso terapêutico
9.
J Clin Oncol ; 38(32): 3773-3784, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-32931399

RESUMO

PURPOSE: Conventional wisdom has rendered patients with brain metastases ineligible for clinical trials for fear that poor survival could mask the benefit of otherwise promising treatments. Our group previously published the diagnosis-specific Graded Prognostic Assessment (GPA). Updates with larger contemporary cohorts using molecular markers and newly identified prognostic factors have been published. The purposes of this work are to present all the updated indices in a single report to guide treatment choice, stratify research, and define an eligibility quotient to expand eligibility. METHODS: A multi-institutional database of 6,984 patients with newly diagnosed brain metastases underwent multivariable analyses of prognostic factors and treatments associated with survival for each primary site. Significant factors were used to define the updated GPA. GPAs of 4.0 and 0.0 correlate with the best and worst prognoses, respectively. RESULTS: Significant prognostic factors varied by diagnosis and new prognostic factors were identified. Those factors were incorporated into the updated GPA with robust separation (P < .01) between subgroups. Survival has improved, but varies widely by GPA for patients with non-small-cell lung, breast, melanoma, GI, and renal cancer with brain metastases from 7-47 months, 3-36 months, 5-34 months, 3-17 months, and 4-35 months, respectively. CONCLUSION: Median survival varies widely and our ability to estimate survival for patients with brain metastases has improved. The updated GPA (available free at brainmetgpa.com) provides an accurate tool with which to estimate survival, individualize treatment, and stratify clinical trials. Instead of excluding patients with brain metastases, enrollment should be encouraged and those trials should be stratified by the GPA to ensure those trials make appropriate comparisons. Furthermore, we recommend the expansion of eligibility to allow for the enrollment of patients with previously treated brain metastases who have a 50% or greater probability of an additional year of survival (eligibility quotient > 0.50).


Assuntos
Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Neoplasias/mortalidade , Neoplasias/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Medicina de Precisão , Prognóstico , Modelos de Riscos Proporcionais
10.
Ann Palliat Med ; 9(5): 2800-2808, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32787372

RESUMO

BACKGROUND: Early palliative care referral for patients with advanced cancer has demonstrable benefits but is underutilized. We sought to characterize medical oncologists' perceptions about palliative care referral in their clinical practices. METHODS: We conducted 4 focus groups with a national sample of medical oncologists to elicit perspectives about the optimal timing of and barriers to palliative care referral for patients with cancer. We used qualitative content analysis to uncover themes related to early integration of palliative care into standard oncologic practice. RESULTS: Study participants readily acknowledged the evidence supporting early palliative care referral. However, medical oncologists identified patient-centered and physician-centered barriers to widespread adoption of early palliative care. Patient-centered barriers included patients' and families' perceptions or misperceptions of the role of palliative care. Additionally, physicians themselves described acting as a barrier to palliative care referral because they were concerned that palliative care physicians may interfere with the plan of care, or offer options that were not endorsed by the medical oncologist. Medical oncologists depicted themselves having authority over the timing of palliative care referral, and as granting limited autonomy to other clinical team members in counseling patients about advanced care planning. CONCLUSIONS: Medical oncologists are hesitant to adopt the practice of early palliative care referral because they are concerned that other physicians may disrupt a patient's treatment plan. Physician-centered barriers may delay integration of palliative care, and future efforts to promote a collaborative approach to advanced care planning may improve patient-centered outcomes through access to early palliative care.


Assuntos
Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Neoplasias , Oncologistas , Médicos , Atitude do Pessoal de Saúde , Humanos , Cuidados Paliativos
11.
Transl Lung Cancer Res ; 9(2): 232-238, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32420062

RESUMO

BACKGROUND: The prognosis of patients with recurrent small cell lung cancer (SCLC) remains poor and treatment options are limited. We performed a multi-institution retrospective cohort study to evaluate the outcome of thoracic reirradiation, identify prognostic factors and assess treatment-related toxicity. METHODS: Data of 33 patients re-irradiated for recurrent SCLC at 4 international university hospitals, were analysed. Overall survival (OS) acute and late toxicities were evaluated and prognostic factors for reirradiation were identified. RESULTS: Reirradiation (Re-RT) was performed at a median interval time of 24 months after the first thoracic radiotherapy series. Median survival after reirradiation was 7 months (range, 1-54 months). The Re-RT dose in EQD2 ranged from 20 to 87.50 Gy with a median of 32.50 Gy. The 1- and 2-year OS were 33% and 17%, respectively. Patients with a good performance status (KPS >70%), absence of extrathoracic disease, reirradiation dose (EQD2) of >40 Gy and a cumulative dose of first plus second series of radiotherapy (EQD2) >90 Gy were associated with improved OS. Acute pulmonary Grade 1-2 toxicity from re-irradiation was recorded in 11 patients (33%) and grade 3 acute toxicity was encountered 1 patient (3%). CONCLUSIONS: Reirradiation for locoregionally recurrent SCLC is safe and shows promising outcomes. Patients reirradiated with doses >40 Gy experienced more favourable survival rates. In contrast, patients with a poor performance status or extrathoracic disease have a poor prognosis and Re-RT should be considered only for symptom control in this group.

12.
Pract Radiat Oncol ; 10(3): 158-173, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32222430

RESUMO

PURPOSE: Several sentinel phase III randomized trials have recently been published challenging traditional radiation therapy (RT) practices for small cell lung cancer (SCLC). This American Society for Radiation Oncology guideline reviews the evidence for thoracic RT and prophylactic cranial irradiation (PCI) for both limited-stage (LS) and extensive-stage (ES) SCLC. METHODS: The American Society for Radiation Oncology convened a task force to address 4 key questions focused on indications, dose fractionation, techniques and timing of thoracic RT for LS-SCLC, the role of stereotactic body radiation therapy (SBRT) compared with conventional RT in stage I or II node negative SCLC, PCI for LS-SCLC and ES-SCLC, and thoracic consolidation for ES-SCLC. Recommendations were based on a systematic literature review and created using a consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: The task force strongly recommends definitive thoracic RT administered once or twice daily early in the course of treatment for LS-SCLC. Adjuvant RT is conditionally recommended in surgically resected patients with positive margins or nodal metastases. Involved field RT delivered using conformal advanced treatment modalities to postchemotherapy volumes is also strongly recommended. For patients with stage I or II node negative disease, SBRT or conventional fractionation is strongly recommended, and chemotherapy should be delivered before or after SBRT. In LS-SCLC, PCI is strongly recommended for stage II or III patients who responded to chemoradiation, conditionally not recommended for stage I patients, and should be a shared decision for patients at higher risk of neurocognitive toxicities. In ES-SCLC, radiation oncologist consultation for consideration of PCI versus magnetic resonance surveillance is strongly recommended. Lastly, the use of thoracic RT is strongly recommended in select patients with ES-SCLC after chemotherapy treatment, including a conditional recommendation in those responding to chemotherapy and immunotherapy. CONCLUSIONS: RT plays a vital role in both LS-SCLC and ES-SCLC. These guidelines inform best clinical practices for local therapy in SCLC.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Feminino , Humanos , Masculino , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/radioterapia
13.
Int J Radiat Oncol Biol Phys ; 107(2): 334-343, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32084525

RESUMO

PURPOSE: Brain metastases are a common sequelae of breast cancer. Survival varies widely based on diagnosis-specific prognostic factors (PF). We previously published a prognostic index (Graded Prognostic Assessment [GPA]) for patients with breast cancer with brain metastases (BCBM), based on cohort A (1985-2007, n = 642), then updated it, reporting the effect of tumor subtype in cohort B (1993-2010, n = 400). The purpose of this study is to update the Breast GPA with a larger contemporary cohort (C) and compare treatment and survival across the 3 cohorts. METHODS AND MATERIALS: A multi-institutional (19), multinational (3), retrospective database of 2473 patients with breast cancer with newly diagnosed brain metastases (BCBM) diagnosed from January 1, 2006, to December 31, 2017, was created and compared with prior cohorts. Associations of PF and treatment with survival were analyzed. Kaplan-Meier survival estimates were compared with log-rank tests. PF were weighted and the Breast GPA was updated such that a GPA of 0 and 4.0 correlate with the worst and best prognoses, respectively. RESULTS: Median survival (MS) for cohorts A, B, and C improved over time (from 11, to 14 to 16 months, respectively; P < .01), despite the subtype distribution becoming less favorable. PF significant for survival were tumor subtype, Karnofsky Performance Status, age, number of BCBMs, and extracranial metastases (all P < .01). MS for GPA 0 to 1.0, 1.5-2.0, 2.5-3.0, and 3.5-4.0 was 6, 13, 24, and 36 months, respectively. Between cohorts B and C, the proportion of human epidermal receptor 2 + subtype decreased from 31% to 18% (P < .01) and MS in this subtype increased from 18 to 25 months (P < .01). CONCLUSIONS: MS has improved modestly but varies widely by diagnosis-specific PF. New PF are identified and incorporated into an updated Breast GPA (free online calculator available at brainmetgpa.com). The Breast GPA facilitates clinical decision-making and will be useful for stratification of future clinical trials. Furthermore, these data suggest human epidermal receptor 2-targeted therapies improve clinical outcomes in some patients with BCBM.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Neoplasias da Mama/patologia , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA1/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias da Mama/genética , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
14.
Neuro Oncol ; 22(9): 1359-1367, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32034917

RESUMO

BACKGROUND: Breast cancer treatment is based on estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2). At the time of metastasis, receptor status can be discordant from that at initial diagnosis. The purpose of this study was to determine the incidence of discordance and its effect on survival and subsequent treatment in patients with breast cancer brain metastases (BCBM). METHODS: A retrospective database of 316 patients who underwent craniotomy for BCBM between 2006 and 2017 was created. Discordance was considered present if the ER, PR, or HER2 status differed between the primary tumor and the BCBM. RESULTS: The overall receptor discordance rate was 132/316 (42%), and the subtype discordance rate was 100/316 (32%). Hormone receptors (HR, either ER or PR) were gained in 40/160 (25%) patients with HR-negative primary tumors. HER2 was gained in 22/173 (13%) patients with HER2-negative primary tumors. Subsequent treatment was not adjusted for most patients who gained receptors-nonetheless, median survival (MS) improved but did not reach statistical significance (HR, 17-28 mo, P = 0.12; HER2, 15-19 mo, P = 0.39). MS for patients who lost receptors was worse (HR, 27-18 mo, P = 0.02; HER2, 30-18 mo, P = 0.08). CONCLUSIONS: Receptor discordance between primary tumor and BCBM is common, adversely affects survival if receptors are lost, and represents a missed opportunity for use of effective treatments if receptors are gained. Receptor analysis of BCBM is indicated when clinically appropriate. Treatment should be adjusted accordingly. KEY POINTS: 1. Receptor discordance alters subtype in 32% of BCBM patients.2. The frequency of receptor gain for HR and HER2 was 25% and 13%, respectively.3. If receptors are lost, survival suffers. If receptors are gained, consider targeted treatment.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Biomarcadores Tumorais , Estrogênios , Humanos , Receptor ErbB-2 , Receptores de Progesterona , Estudos Retrospectivos
15.
J Clin Oncol ; 38(10): 1019-1029, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32058845

RESUMO

PURPOSE: Radiation dose to the neuroregenerative zone of the hippocampus has been found to be associated with cognitive toxicity. Hippocampal avoidance (HA) using intensity-modulated radiotherapy during whole-brain radiotherapy (WBRT) is hypothesized to preserve cognition. METHODS: This phase III trial enrolled adult patients with brain metastases to HA-WBRT plus memantine or WBRT plus memantine. The primary end point was time to cognitive function failure, defined as decline using the reliable change index on at least one of the cognitive tests. Secondary end points included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported symptom burden. RESULTS: Between July 2015 and March 2018, 518 patients were randomly assigned. Median follow-up for alive patients was 7.9 months. Risk of cognitive failure was significantly lower after HA-WBRT plus memantine versus WBRT plus memantine (adjusted hazard ratio, 0.74; 95% CI, 0.58 to 0.95; P = .02). This difference was attributable to less deterioration in executive function at 4 months (23.3% v 40.4%; P = .01) and learning and memory at 6 months (11.5% v 24.7% [P = .049] and 16.4% v 33.3% [P = .02], respectively). Treatment arms did not differ significantly in OS, intracranial PFS, or toxicity. At 6 months, using all data, patients who received HA-WBRT plus memantine reported less fatigue (P = .04), less difficulty with remembering things (P = .01), and less difficulty with speaking (P = .049) and using imputed data, less interference of neurologic symptoms in daily activities (P = .008) and fewer cognitive symptoms (P = .01). CONCLUSION: HA-WBRT plus memantine better preserves cognitive function and patient-reported symptoms, with no difference in intracranial PFS and OS, and should be considered a standard of care for patients with good performance status who plan to receive WBRT for brain metastases with no metastases in the HA region.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Cognição/efeitos da radiação , Hipocampo/efeitos da radiação , Memantina/uso terapêutico , Antiparkinsonianos/uso terapêutico , Neoplasias Encefálicas/secundário , Quimiorradioterapia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Qualidade de Vida , Lesões por Radiação/etiologia , Lesões por Radiação/prevenção & controle , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos
16.
J Neurooncol ; 146(1): 121-130, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31741234

RESUMO

PURPOSE: Practice patterns vary for adjuvant treatment of 1p/19q-codeleted oligodendroglioma patients. This study evaluates the outcomes of adjuvant (aRT) versus salvage radiation therapy (sRT) in a multi-institutional cohort. METHODS: Oligodendroglioma patients with confirmed 1p/19q codeletion who were treated with RT with or without chemotherapy from 2000 to 2017 at four tertiary centers were retrospectively reviewed. Overall survival (OS), post-RT progression-free survival (PFS), freedom-from-RT (FFRT), and radiation necrosis (RN) rates were determined using Kaplan-Meier analyses. OS1/PFS1 were defined from the initial surgery. OS2/PFS2 were defined from the RT start-date. Multivariable analyses (MVAs) of prognostic factors for OS and PFS were performed with Cox regression. RESULTS: One hundred eighty-six patients were identified: 124(67%) received aRT and 62(33%) received sRT; of sRT patients, 58% were observed after surgery while 42% received chemotherapy without aRT. The median time from initial diagnosis to sRT was 61 months, and 74% had reoperations before sRT. sRT had longer OS1 than aRT (94% vs. 69% at 10 years, p = 0.03) and PFS1 (10-year PFS of 80% vs. 68%, p = 0.03), though sRT was not associated with significantly different OS1/PFS1 on MVAs. Chemotherapy did not delay sRT compared to observation and had worse PFS2 (42% vs. 79% at 5 years, p = 0.08). Higher RT dose was not associated with improved clinical outcomes but was associated with higher symptomatic RN rate (15% vs. 0% at 2 years, p = 0.003). CONCLUSIONS: Delaying RT for selected oligodendroglioma patients appears safe. Adjuvant chemotherapy does not delay sRT longer than observation and may be associated with worse PFS after RT.


Assuntos
Cromossomos Humanos Par 19/genética , Cromossomos Humanos Par 1/genética , Deleção de Genes , Oligodendroglioma/mortalidade , Padrões de Prática Médica/estatística & dados numéricos , Radioterapia Adjuvante/mortalidade , Terapia de Salvação , Adulto , Idoso , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Oligodendroglioma/genética , Oligodendroglioma/patologia , Oligodendroglioma/radioterapia , Aceitação pelo Paciente de Cuidados de Saúde , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
17.
Transl Lung Cancer Res ; 8(Suppl 2): S153-S162, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31673520

RESUMO

Small cell lung cancer has been a difficult disease to treat with poor survival and few significant improvements in outcomes in the last three decades. Most recently the addition of atezolizumab to chemotherapy in the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) resulted in improved overall survival and progression-free survival compared to chemotherapy alone. Recent randomized studies examining both consolidative thoracic radiotherapy and prophylactic cranial irradiation (PCI) in ES-SCLC have impacted the utilization of these interventions. The approval of immune checkpoint inhibitors (ICIs) to platinum/etoposide chemotherapy for the treatment of ES-SCLC in the front-line setting may also further impact the role of radiotherapy in this disease. In this article, we review the current evidence supporting thoracic radiotherapy in ES-SCLC and discuss the promising therapeutic implications of thoracic radiation in light of the inclusion of ICIs. We also address how the increasing routine use of surveillance brain magnetic resonance imaging (MRI) and ICIs may diminish the use of PCI in ES-SCLC.

18.
CNS Oncol ; 8(3): CNS39, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31535562

RESUMO

Pleomorphic xanthoastrocytoma (PXA) is a rare primary CNS tumor. Recent advances in the molecular characterization are helping to define subtypes of tumor. The discovery of BRAF mutations within a substantial percentage of PXA fosters a clearer understanding of the pathophysiology of these tumors with clear prognostic and therapeutic implications. These findings are expected to provide insight into the spectrum of clinical behavior observed in PXA, ranging from cure with surgery to diffuse dissemination throughout the neuraxis. This review details the clinical presentation including radiographic appearance of PXA. Pathology, including molecular pathology is discussed. Therapeutic management including surgical resection, radiotherapy and systemic therapies are reviewed.


Assuntos
Astrocitoma/patologia , Astrocitoma/terapia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Terapia Combinada , Humanos , Prognóstico
19.
Int J Radiat Oncol Biol Phys ; 105(2): 245-246, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492382
20.
Pract Radiat Oncol ; 9(5): 362-370, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31202831

RESUMO

PURPOSE: Multidisciplinary communication and collaboration are key to planning and delivering end-of-life care for patients with advanced and metastatic cancer. We sought to characterize medical oncologists' perspectives on the role of radiation oncologists in end-of-life care. MATERIALS AND METHODS: A sample of US medical oncologists was recruited using snowball sampling methods. Audio recordings of 4 professionally moderated focus groups were transcribed. Investigators from diverse backgrounds (medical oncology, radiation oncology, critical care medicine, palliative care, and public health) independently reviewed each transcript. Qualitative content analysis was used to create consensus codes that were applied to subsequent focus group transcripts in an iterative process. RESULTS: Medical oncologists expressed complex views regarding the role of radiation oncologists in end-of-life care. Identified themes included the limited role of radiation oncologists, territorial concerns, capability, and desire of radiation oncologists in this realm, and the need for communication between providers. Radiation oncologists were compared with surgeons, whose interaction with patients ceased after their service had been performed. In this regard, control of palliative care referral or end-of-life care discussions was thought to be in the territory of medical oncologists who had longitudinal relationships with patients from diagnosis. Medical oncologists were concerned about the capability of radiation oncologists to accurately prognosticate, and stated radiation oncologists lacked knowledge of subsequent lines of systemic therapy available to patients. Radiation oncologists' fear of upsetting medical oncologists was thought to be justified if they engaged in end-of-life care planning without direct permission from the referring medical oncologist. CONCLUSIONS: Participation of radiation oncologists in end-of-life care planning was viewed with skepticism by medical oncologists. Radiation oncologists should focus on increasing open communication and teamwork with medical oncologists and demonstrate their ability to prognosticate and counsel patients regarding end-of-life care decisions.


Assuntos
Cuidados Paliativos/métodos , Radio-Oncologistas/psicologia , Assistência Terminal/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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