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1.
Risk Anal ; 42(3): 470-486, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34169544

RESUMO

This article examined trust, perceived risks and benefits, and normative acceptance associated with using breeding and genetic engineering (GE) to restore American chestnut (AC) trees. Questionnaires were completed by a random representative sample of the public in the United States (n = 278) and a purposive sample of forest interest groups (FIG) such as scientists and managers (n = 195). These concepts were examined in relation to breeding (breed the AC with chestnut trees from Asia) and GE (add the oxalate oxidase [OxO] gene from bread wheat to the AC) approaches for mitigating chestnut blight and restoring AC trees. The public sample considered adding the gene from bread wheat (GE) to be more beneficial and slightly more acceptable, but also slightly riskier, compared to the breeding approach. The FIGs viewed the breeding approach to be more acceptable, less risky, and more beneficial than the GE approach. The FIGs viewed both approaches as less risky, more beneficial, and more acceptable than did the public sample. Path analysis showed that: (i) perceived environmental benefits were the strongest predictors of normative acceptance of both approaches for the public sample, (ii) perceived environmental risks were the strongest predictors of acceptance of both approaches for the FIGs, (iii) human benefits and risks were mostly unrelated to acceptance, and (iv) trust in government agencies charged with managing forests was only weakly associated with benefits, risks, and acceptance. Implications of these results for both research and management were discussed.


Assuntos
Árvores , Confiança , Florestas , Humanos , Doenças das Plantas , Medição de Risco , Estados Unidos
2.
New Phytol ; 213(3): 1000-1021, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28079940

RESUMO

1000 I. 1000 II. 1001 III. 1014 IV. 1015 V. 1016 1016 References 1016 SUMMARY: Genetic engineering (GE) can be used to improve forest plantation productivity and tolerance of biotic and abiotic stresses. However, gene flow from GE forest plantations is a large source of ecological, social and legal controversy. The use of genetic technologies to mitigate or prevent gene flow has been discussed widely and should be technically feasible in a variety of plantation taxa. However, potential ecological effects of such modifications, and their social acceptability, are not well understood. Focusing on Eucalyptus, Pinus, Populus and Pseudotsuga - genera that represent diverse modes of pollination and seed dispersal - we conducted in-depth reviews of ecological processes associated with reproductive tissues. We also explored potential impacts of various forms of reproductive modification at stand and landscape levels, and means for mitigating impacts. We found little research on potential reactions by the public and other stakeholders to reproductive modification in forest plantations. However, there is considerable research on related areas that suggest key dimensions of concern and support. We provide detailed suggestions for research to understand the biological and social dimensions of containment technologies, and consider the role of regulatory and market restrictions that obstruct necessary ecological and genetic research.


Assuntos
Biodiversidade , Florestas , Sociedades , Animais , Comportamento Alimentar , Engenharia Genética , Reprodução
3.
Nat Cancer ; 3(11): 1300-1317, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36434392

RESUMO

Five-year survival for human papilloma virus-unrelated head and neck squamous cell carcinomas remain below 50%. We assessed the safety of administering combination hypofractionated stereotactic body radiation therapy with single-dose durvalumab (anti-PD-L1) neoadjuvantly (n = 21) ( NCT03635164 ). The primary endpoint of the study was safety, which was met. Secondary endpoints included radiographic, pathologic and objective response; locoregional control; progression-free survival; and overall survival. Among evaluable patients at an early median follow-up of 16 months (448 d or 64 weeks), overall survival was 80.1% with 95% confidence interval (95% CI) (62.0%, 100.0%), locoregional control and progression-free survival were 75.8% with 95% CI (57.5%, 99.8%), and major pathological response or complete response was 75% with 95% exact CI (51.6%, 100.0%). For patients treated with 24 Gy, 89% with 95% CI (57.1%, 100.0%) had MPR or CR. Using high-dimensional multi-omics and spatial data as well as biological correlatives, we show that responders had: (1) an increase in effector T cells; (2) a decrease in immunosuppressive cells; and (3) an increase in antigen presentation post-treatment.


Assuntos
Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Radiocirurgia , Humanos , Neoplasias de Cabeça e Pescoço/terapia , Terapia Neoadjuvante/efeitos adversos , Infecções por Papillomavirus/complicações , Radiocirurgia/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia
6.
J Clin Endocrinol Metab ; 93(2): 393-9, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18029460

RESUMO

CONTEXT: Radiation therapy is a potentially curative treatment for corticotroph adenomas refractory to surgery. Protons have an advantage over photons (x-rays) by depositing energy at the target with no exit dose, providing a lower dose to adjacent normal tissues. Until recently, proton stereotactic radiotherapy (PSR) was available at only two U.S. centers; use will increase as proton facilities are under development. OBJECTIVE: Our objective was to evaluate the efficacy and safety of PSR for persistent Cushing's disease (CD) and Nelson's syndrome (NS). DESIGN: This was a retrospective review of 38 patients (33 with CD and five with NS) treated between 1992 and 2005. PARTICIPANTS: All patients had transsphenoidal surgery without biochemical cure. Four had previous irradiation with photons. The patients with NS underwent bilateral adrenalectomy 29-228 months (median 40) before PSR. INTERVENTION: Single-fraction PSR was delivered at a median dose of 20 Cobalt Gray Equivalents (range 15-20) on 1 treatment day. MAIN OUTCOME MEASURES: Complete response (CR) was defined as sustained (> or =3 months) normalization of urinary free cortisol off medical therapy. CR in NS was based on normalization of plasma corticotropin. RESULTS: At a median follow-up of 62 months (range 20-136), CR was achieved in five patients (100%) with NS and 17 (52%) patients with CD. Among all patients with CR, median time to CR was 18 months (range 5-49). No secondary tumors were noted on follow-up magnetic resonance imaging scans, and there was no clinical evidence of optic nerve damage, seizure, or brain injury. There were 17 patients (52%) who developed new pituitary deficits. CONCLUSIONS: PSR is effective for patients with persistent corticotroph adenomas with low morbidity after a median follow-up of 62 months; longer follow-up is warranted for late radiation-related sequelae.


Assuntos
Síndrome de Nelson/cirurgia , Hipersecreção Hipofisária de ACTH/cirurgia , Terapia com Prótons , Radiocirurgia/métodos , Adolescente , Adulto , Feminino , Humanos , Hidrocortisona/urina , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Síndrome de Nelson/urina , Hipersecreção Hipofisária de ACTH/urina , Indução de Remissão , Estudos Retrospectivos
7.
Urol Oncol ; 26(4): 372-7, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18367113

RESUMO

OBJECTIVES: To compare the impact of bicalutamide (B) vs. luteinizing hormone-releasing hormone analogues (LHRHa) on prostate volume, patient-reported side effects, and postimplant urinary toxicity in the setting of interstitial brachytherapy for early-stage prostate cancer. METHODS: Between May 1998 and January 2004, 81 patients received androgen-deprivation therapy (ADT) for cytoreduction prior to interstitial brachytherapy alone. Fifty-six patients received LHRHa and 25 patients received B. Prostate volumes were measured prospectively prior to initiating therapy, and then intraoperatively at the time of implant by a single, blinded ultrasonographer. Patient-reported quality of life data were obtained prospectively, and postimplant urinary toxicity (catheter dependency and need for surgical intervention) was recorded during follow-up. Median follow-up was 53 (range 23-78) months. RESULTS: The median percentage prostate volume reductions of 26% for B and 32% for LHRHa were not statistically different (P = 0.61). Decrements in libido (92% vs. 44%, P < 0.001) and erectile function (79% vs. 20%) were reported in more respondents treated with LHRHa than B. The incidence of recatheterization (28% vs. 24%, P = 0.34), and the need for subsequent surgical intervention (11% vs. 4%, P = 0.16) were similar for patients treated with LHRHa and B. CONCLUSIONS: The degree of prostate downsizing with B is similar to that achieved with LHRHa. B was associated with fewer patient-reported sexual side effects and similar urinary morbidity. A randomized trial is needed to establish whether LHRHa or B should be the standard of care for prostate downsizing before interstitial brachytherapy.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Anilidas/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Braquiterapia , Gosserrelina/uso terapêutico , Leuprolida/uso terapêutico , Nitrilas/uso terapêutico , Neoplasias da Próstata/terapia , Compostos de Tosil/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Gosserrelina/efeitos adversos , Humanos , Leuprolida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Morbidade
9.
Brachytherapy ; 6(4): 267-71, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17959423

RESUMO

PURPOSE: We examined whether prostate volume reduction after a short course of androgen deprivation (AD) lowered the risks of acute and chronic urinary morbidity related to radioactive seed implantation for low-risk prostate cancer. METHODS AND MATERIALS: Eighty-one patients received AD for cytoreduction before interstitial brachytherapy alone. Urinary morbidity was carefully assessed for all patients during a median followup of 53 (range, 23-78) months after treatment. Outcomes were then compared with those of a control group of 81 patients who were matched 1:1 based on identical prostate volume measured at the time of radioactive seed implant, but who had not received AD. RESULTS: Despite effective cytoreduction (median, 30% prostate volume reduction) with AD, prolonged catheterization was required significantly more often for patients who had received AD when compared with the control group of patients who were implanted at identical prostate volumes but who had not received AD (27% vs. 9%, p = 0.02). This finding remained statistically significant on multivariate analysis (p = 0.04). Surgical intervention (9% vs. 4%, p = 0.09) and subsequent urinary incontinence (4% vs. 1%, p = 0.16) were also more frequent among patients who had received AD when compared with implant volume-matched controls. CONCLUSIONS: Patients who achieved smaller prostate volumes through the use of AD maintained a significantly elevated risk (threefold) for urinary complications, commensurate with their initially large prostate volume, when compared with a control group of patients who were implanted at identical prostate volumes but who had not received AD. Therefore, patients presenting with larger prostate glands that would warrant a short course of AD before implant should be counseled accordingly when discussing options for local therapy.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Disuria/etiologia , Próstata/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Idoso , Humanos , Masculino , Terapia Neoadjuvante , Neoplasias da Próstata/patologia , Risco , Cateterismo Urinário
10.
Neurosurg Focus ; 23(6): E5, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18081482

RESUMO

OBJECT: Photon energy deposition from gamma or photon sources follows the law of exponential decay. Consequently, energy is deposited over the entire path of the radiation beam, resulting in dose distribution before and after the target is reached. In contrast, the physical properties of protons are such that energy deposition occurs with no exit dose beyond the target volume. Therefore, relative to photons, proton beams represent a superior platform for the administration of radiosurgery. METHODS: In this review, the authors will discuss the fundamental principles underlying photon- and proton-based stereotactic radiosurgery (SRS). The clinical efficacy of proton-based SRS in the treatment of arteriovenous malformations, vestibular schwannomas, and pituitary adenomas is reviewed. RESULTS: Direct comparisons of clinical results attained using photon- and proton-based SRS are confounded by a bias toward reserving proton beams for the treatment of larger and more complex lesions. Despite this bias, the clinical outcomes for proton-based SRS have been excellent and have been at least comparable to those for photon-based treatments. CONCLUSIONS: The physical properties of proton radiation offer superior conformality in dose distribution relative to photon irradiation. This advantage becomes more apparent as the lesion size increases and will probably be magnified with the development of intensity-modulated proton techniques.


Assuntos
Encefalopatias/cirurgia , Neurocirurgia/métodos , Terapia com Prótons , Radiocirurgia , Humanos
11.
Pract Radiat Oncol ; 7(1): 4-12, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27663933

RESUMO

PURPOSE: The purpose is to provide an update the Bone Metastases Guideline published in 2011 based on evidence complemented by expert opinion. The update will discuss new high-quality literature for the 8 key questions from the original guideline and implications for practice. METHODS AND MATERIALS: A systematic PubMed search from the last date included in the original Guideline yielded 414 relevant articles. Ultimately, 20 randomized controlled trials, 32 prospective nonrandomized studies, and 4 meta-analyses/pooled analyses were selected and abstracted into evidence tables. The authors synthesized the evidence and reached consensus on the included recommendations. RESULTS: Available literature continues to support pain relief equivalency between single and multiple fraction regimens for bone metastases. High-quality data confirm single fraction radiation therapy may be delivered to spine lesions with acceptable late toxicity. One prospective, randomized trial confirms both peripheral and spine-based painful metastases can be successfully and safely palliated with retreatment for recurrence pain with adherence to published dosing constraints. Advanced radiation therapy techniques such as stereotactic body radiation therapy lack high-quality data, leading the panel to favor its use on a clinical trial or when results will be collected in a registry. The panel's conclusion remains that surgery, radionuclides, bisphosphonates, and kyphoplasty/vertebroplasty do not obviate the need for external beam radiation therapy. CONCLUSION: Updated data analysis confirms that radiation therapy provides excellent palliation for painful bone metastases and that retreatment is safe and effective. Although adherence to evidence-based medicine is critical, thorough expert radiation oncology physician judgment and discretion regarding number of fractions and advanced techniques are also essential to optimize outcomes when considering the patient's overall health, life expectancy, comorbidities, tumor biology, anatomy, previous treatment including prior radiation at or near current site of treatment, tumor and normal tissue response history to local and systemic therapies, and other factors related to the patient, tumor characteristics, or treatment.


Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Cuidados Paliativos , Guias de Prática Clínica como Assunto , Difosfonatos/uso terapêutico , Medicina Baseada em Evidências , Humanos , Cifoplastia , PubMed , Compostos Radiofarmacêuticos , Vertebroplastia
12.
Brachytherapy ; 16(6): 1083-1090, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28988661

RESUMO

BACKGROUND: This collaborative practice parameter technical standard has been created between the American College of Radiology and American Brachytherapy Society to guide the usage of electronically generated low energy radiation sources (ELSs). It refers to the use of electronic X-ray sources with peak voltages up to 120 kVp to deliver therapeutic radiation therapy. MAIN FINDINGS: The parameter provides a guideline for utilizing ELS, including patient selection and consent, treatment planning, and delivery processes. The parameter reviews the published clinical data with regard to ELS results in skin, breast, and other cancers. CONCLUSIONS: This technical standard recommends appropriate qualifications of the involved personnel. The parameter reviews the technical issues relating to equipment specifications as well as patient and personnel safety. Regarding suggestions for educational programs with regard to this parameter,it is suggested that the training level for clinicians be equivalent to that for other radiation therapies. It also suggests that ELS must be done using the same standards of quality and safety as those in place for other forms of radiation therapy.


Assuntos
Radioterapia/instrumentação , Radioterapia/normas , Braquiterapia/instrumentação , Braquiterapia/métodos , Braquiterapia/normas , Neoplasias da Mama/radioterapia , Feminino , Humanos , Oncologia/educação , Neoplasias/radioterapia , Segurança do Paciente , Seleção de Pacientes , Radioterapia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Planejamento da Radioterapia Assistida por Computador/normas , Neoplasias Cutâneas/radioterapia , Sociedades Médicas , Estados Unidos
13.
Phys Med Biol ; 51(10): 2493-501, 2006 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-16675865

RESUMO

This work looks at the feasibility of an online adaptive radiation therapy concept that would detect the daily position and shape of the patient, and would then correct the daily treatment to account for any changes compared with planning position. In particular, it looks at the possibility of developing algorithms to correct for large complicated shape change. For co-planar beams, the dose in an axial plane is approximately associated with the positions of a single multi-leaf collimator (MLC) pair. We start with a primary plan, and automatically generate several secondary plans with gantry angles offset by regular increments. MLC sequences for each plan are calculated keeping monitor units (MUs) and number of segments constant for a given beam (fluences are different). Bulk registration (3D) of planning and daily CT images gives global shifts. Slice-by-slice (2D) registration gives local shifts and rotations about the longitudinal axis for each axial slice. The daily MLC sequence is then created for each axial slice/MLC leaf pair combination, by taking the MLC positions from the pre-calculated plan with the nearest rotation, and shifting using a beam's-eye-view calculation to account for local linear shifts. A planning study was carried out using two head and neck region MR images of a healthy volunteer which were contoured to simulate a base-of-tongue treatment: one with the head straight (used to simulate the planning image) and the other with the head tilted to the left (the daily image). Head and neck treatment was chosen to evaluate this technique because of its challenging nature, with varying internal and external contours, and multiple degrees of freedom. Shape change was significant: on a slice-by-slice basis, local rotations in the daily image varied from 2 to 31 degrees, and local shifts ranged from -0.2 to 0.5 cm and -0.4 to 0.0 cm in right-left and posterior-anterior directions, respectively. The adapted treatment gave reasonable target coverage (100%, 90% and 80% of the base-of-tongue, left nodes and right nodes, respectively, receiving the daily prescription dose), and kept the daily cord dose below the limit used in the original plan (65%, equivalent to 46 Gy over 35 fractions). Most of the loss of coverage was due to one shoulder being raised more superior relative to the other shoulder compared with the plan. This type of skew-like motion is not accounted for by the proposed ART technique. In conclusion, this technique has potential to correct for fairly extreme daily changes in patient setup, but some control of the daily position would still be necessary. Importantly, it was possible to combine treatments from different plans (MLC sequences) to correct for position and shape change.


Assuntos
Algoritmos , Artefatos , Inteligência Artificial , Modelos Biológicos , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Tamanho Corporal , Simulação por Computador , Estudos de Viabilidade , Retroalimentação , Humanos , Movimento (Física) , Sistemas On-Line , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Neoplasias da Língua/fisiopatologia , Neoplasias da Língua/radioterapia
15.
Pract Radiat Oncol ; 6(4): 217-225, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27211230

RESUMO

PURPOSE: To present evidence-based guidelines for radiation therapy in treating glioblastoma not arising from the brainstem. METHODS AND MATERIALS: The American Society for Radiation Oncology (ASTRO) convened the Glioblastoma Guideline Panel to perform a systematic literature review investigating the following: (1) Is radiation therapy indicated after biopsy/resection of glioblastoma and how does systemic therapy modify its effects? (2) What is the optimal dose-fractionation schedule for external beam radiation therapy after biopsy/resection of glioblastoma and how might treatment vary based on pretreatment characteristics such as age or performance status? (3) What are ideal target volumes for curative-intent external beam radiation therapy of glioblastoma? (4) What is the role of reirradiation among glioblastoma patients whose disease recurs following completion of standard first-line therapy? Guideline recommendations were created using predefined consensus-building methodology supported by ASTRO-approved tools for grading evidence quality and recommendation strength. RESULTS: Following biopsy or resection, glioblastoma patients with reasonable performance status up to 70 years of age should receive conventionally fractionated radiation therapy (eg, 60 Gy in 2-Gy fractions) with concurrent and adjuvant temozolomide. Routine addition of bevacizumab to this regimen is not recommended. Elderly patients (≥70 years of age) with reasonable performance status should receive hypofractionated radiation therapy (eg, 40 Gy in 2.66-Gy fractions); preliminary evidence may support adding concurrent and adjuvant temozolomide to this regimen. Partial brain irradiation is the standard paradigm for radiation delivery. A variety of acceptable strategies exist for target volume definition, generally involving 2 phases (primary and boost volumes) or 1 phase (single volume). For recurrent glioblastoma, focal reirradiation can be considered in younger patients with good performance status. CONCLUSIONS: Radiation therapy occupies an integral role in treating glioblastoma. Whether and how radiation therapy should be applied depends on characteristics specific to tumor and patient, including age and performance status.


Assuntos
Neoplasias Encefálicas/radioterapia , Glioblastoma/radioterapia , Fracionamento da Dose de Radiação , Guias como Assunto , Humanos , Masculino , Estudos Prospectivos , Estados Unidos
17.
Int J Radiat Oncol Biol Phys ; 59(1): 112-6, 2004 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-15093906

RESUMO

PURPOSE: Stereotactic radiosurgery (SRS) has become a minimally invasive treatment modality for patients with refractory trigeminal neuralgia. It is unclear, however, how best to treat patients with pain that is refractory or recurrent after initial SRS. We report on treatment outcomes and quality of life for patients treated with repeated SRS for refractory or recurrent trigeminal neuralgia. METHODS AND MATERIALS: Between June 1996 and June 2001, 112 patients with trigeminal neuralgia were treated with SRS at the University of Maryland Medical Center. Eighteen patients underwent repeat SRS 3-42 months (median, 8 months) after initial radiosurgery because of unsatisfactory or unsustained pain relief. Patients received a median prescription dose of 75 and 70 Gy, respectively, for the first and second treatments. Self-reports of pain control were assessed with a standard questionnaire containing the complete Barrow Neurologic Institute Pain Scale. RESULTS: The median follow-up was 37.5 months (range, 12-68 months) after initial SRS and 24.5 months (range, 6-65 months) after repeat SRS. For the 18 patients in this series, the percentage of patients reporting excellent, good, fair, and poor responses after the initial and repeat SRS was 50%, 28%, 6%, and 16% and 45%, 33%, 0%, and 22%, respectively. None of the 3 patients with pain refractory to initial SRS responded to repeat SRS. Among those with recurrent pain after initial SRS, 14 patients (93%) achieved excellent or good pain outcomes after repeat SRS. The actuarial analysis revealed a 1-year recurrence rate of 22%, with no patients reporting recurrent pain after 9 months of follow-up. Two patients (11%) reported new or increased facial numbness after retreatment, which was described as bothersome by one. Repeat SRS resulted in a median 60% improvement in quality of life, and 56% of patients believed that the procedure was successful. CONCLUSION: Despite a modest dose reduction, repeat SRS provided similar rates of complete pain control as the initial procedure, but was not effective for patients with no response to initial treatment. Repeat SRS was more efficacious for those patients who experienced longer periods of pain relief after the initial SRS. The incidence of complications was not significantly different from that observed for initial SRS. In this series, most patients had significant improvements in quality of life.


Assuntos
Radiocirurgia/instrumentação , Neuralgia do Trigêmeo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Recidiva , Resultado do Tratamento
18.
Int J Radiat Oncol Biol Phys ; 56(4): 1147-53, 2003 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-12829153

RESUMO

PURPOSE: To assess the safety, efficacy, and quality of life (QOL) associated with radiosurgical treatment for trigeminal neuralgia (TN). METHODS AND MATERIALS: Between June 1996 and June 2001, 112 patients with TN refractory to medical or surgical management were treated with gamma knife radiosurgery (GKRS) at the University of Maryland Medical Center. A median prescription dose of 75 Gy (range: 70-80 Gy) was delivered to the involved trigeminal nerve root entry zone. Treatment outcomes were assessed through patient self-reports of pain control and medication usage during follow-up visits. In addition, patients responded to a standard questionnaire containing the Barrow Neurologic Institute Pain Scale (BNI) and selected sections of the McGill Pain Scale. Treatment outcomes and objective quality of life measures were also addressed. RESULTS: Ninety-six patients (86%) completed questionnaires for a median follow-up of 30 months (range: 8-66 months). Seventy-four patients (77%) reported pain relief occurring after a median of 3 weeks (range: 0-24 weeks) after GKRS. A decrease in medication usage was noted in 66% of patients. Actuarial analysis demonstrated 1-year, 2-year, and 3-year recurrence rates of 23%, 33%, and 39%, respectively. Response to treatment was associated with lack of prior surgical treatment (p = 0.03) and less than 50 months' pain duration before GKRS (p = 0.04). Patients who described their TN pain as more severe than their worst non-TN headache pain (McGill Pain Scale IV-V vs. I-III) were also more likely to respond to treatment (p < 0.001). Seven (7.3%) patients reported new or increased trigeminal dysfunction; however, only 3.1% reported these symptoms as bothersome (BNI III-IV). Patients with sustained pain relief reported an average of 100% improvement in their QOL as a direct result of pain relief after GKRS, and 100% believed that the procedure was successful. Furthermore, among those patients with temporary pain relief and subsequent recurrence, 65% felt their treatment was a success with an average of 80% improvement in their QOL. CONCLUSIONS: GKRS provides significant pain relief and improves QOL in the majority of patients treated for TN, with few bothersome side effects. Patients with both temporary and sustained responses to treatment realized significant improvements in QOL after GKRS, and considered their treatment successful. Longer follow-up of these patients may reveal additional recurrences highlighting the importance of studies evaluating repeat GKRS and optimization of current treatment techniques and patient selection.


Assuntos
Radiocirurgia/métodos , Neuralgia do Trigêmeo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Qualidade de Vida , Radiocirurgia/efeitos adversos , Resultado do Tratamento
19.
Int J Radiat Oncol Biol Phys ; 60(2): 537-41, 2004 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-15380590

RESUMO

PURPOSE: To review our results with gamma knife surgery (GKS) in the treatment of trigeminal neuralgia (TN), and to determine whether pain relief, medication usage, and the development of facial numbness are affected by trigeminal nerve compression, MRI imaging quality, or brainstem radiation dose. METHODS AND MATERIALS: One hundred twelve patients with TN refractory to medical or surgical management were treated at the University of Maryland Gamma Knife Center between June 1996 and July 2001. Patients were treated using a 4-mm shot to the trigeminal nerve, at a point 2-4 mm anterior to the root entry zone of the nerve into the pons. The median dose prescribed was 75 Gy (range, 60-80 Gy). T1- and T2-weighted, axial, 1.5-mm-thick MRI images were obtained using three-dimensional gradient echo acquisition after contrast injection for treatment planning. MRI images were evaluated for imaging quality (i.e., the adequacy of visualization of the affected prepontine trigeminal nerve), the presence of trigeminal nerve compression, and the brainstem dose. Follow-up data were obtained via telephone interviews, and patients were asked to rate their pre-GKS and post-GKS pain using the Barrow Neurological Institute (BNI) Pain Intensity Scale. Patients were also asked about side effects from GKS and were asked to rate any facial numbness on the BNI Facial Numbness Scale. Medication use, time to pain response, and duration of relief were also evaluated. RESULTS: Ninety-six patients who had follow-up data were included in the analysis. Eighty-six patients (89.6%) responded to GKS with an improvement in BNI pain class. Ten patients (10.4%) were found to have an MRI of poor quality, 30 (31.3%) fair quality, and 56 (58.3%) good quality. Forty-two (43.8%) received 10% of the maximal dose to the brainstem edge, whereas 54 (56.2%) received 20%. Eleven (11.5%) patients were found to have obvious nerve compression by MRI. Imaging quality (p = 0.1863), presence of compression (p = 0.1147), and brainstem dose (p = 0.3168) did not correlate with treatment response. There was also no correlation between these variables (MRI quality, compression, and brainstem dose) and medication use (p = 0.5372, p = 0.0913, p = 0.6832, respectively). Facial numbness was the only side effect experienced. Thirteen patients reported varying degrees of facial numbness, but there was no correlation between imaging quality (p = 0.0600), brainstem dose (p = 0.6773), and presence of compression (p = 0.5785) with the development of facial numbness. CONCLUSIONS: Gamma knife surgery is effective in the treatment of TN and has a favorable side effect profile. Treatment response and the development of facial numbness do not correlate with MRI imaging quality, presence of nerve compression, or radiation dose to the brainstem.


Assuntos
Tronco Encefálico/efeitos da radiação , Imageamento por Ressonância Magnética , Radiocirurgia , Neuralgia do Trigêmeo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Tronco Encefálico/patologia , Feminino , Humanos , Hipestesia/etiologia , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Masculino , Pessoa de Meia-Idade , Síndromes de Compressão Nervosa/diagnóstico , Radiocirurgia/efeitos adversos , Radiocirurgia/instrumentação , Dosagem Radioterapêutica , Doenças do Nervo Trigêmeo/diagnóstico , Doenças do Nervo Trigêmeo/etiologia , Neuralgia do Trigêmeo/diagnóstico
20.
Neurosurg Focus ; 13(3): ecp1, 2002 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-15844877

RESUMO

OBJECT: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF cytokine family, which mediates programmed cell death (apoptosis) selectively in tumor cells. The selective tumoricidal activity of TRAIL is believed to be modulated by agonistic (DR4 and DR5) and antagonistic receptors (DcR1 and DcR2), which appear to compete for ligand binding. Because TRAIL is expressed in a wide range of tissues, including brain, kidney, and spleen, and seems consistently to induce cell death in tumor cells, the cytokine has been identified as a promising approach for selectively inducing tumor cell death. In this study, the authors examine the importance of TRAIL's receptors in both its selectivity for tumor cells and its ability to induce apoptosis. METHODS: The authors first examined sensitivity to TRAIL and expression of TRAIL receptors in four established and four primary cultured glioma cell lines by using viability and fluorescent apoptosis assays. They then evaluated DR5 expression and JNK, caspase 3, and caspase 7 activation by conducting immunoblot analyses. Reverse transcriptase-polymerase chain reaction (RTPCR) was performed to study expression of DR4, DR5, DcR1, and DcR2. The DR5 transcripts from one TRAIL-sensitive, one partially TRAIL-resistant, and one TRAIL-resistant cell line were subsequently sequenced. The expression of TRAIL receptors in normal and glial brain tumor pathological specimens were then compared using immunohistochemistry. Finally, to study the direct effects of DR5 on glioma cells, the authors conducted transient and stable transfections of the full-length DR5 transcript into glioma cells with and without preestablished overexpression of the antiapoptotic gene bcl-2. The established glioma cell lines T98G and U87MG, and all primary cell lines, were apoptotic at greater than or equal to 100 ng/ml TRAIL. The A172 cells, by contrast, were susceptible only with cycloheximide, whereas U373MG cells were not susceptible to TRAIL. The JNK, caspase 3, and caspase 7 activity evaluated after treatment with TRAIL showed that TRAIL-sensitive cell lines exhibited downstream caspase activation, whereas TRAIL-resistant cells did not. The DR5 sequences in T98G, A172, and U373MG cell lines were identical to published sequences despite these differences in sensitivity to TRAIL. The RT-PCR performed on extracts from the eight glioma cell lines showed that all expressed DR5. Immunohistochemistry revealed ubiquitous expression of DR5 in glioma specimens, with an associated lack of decoy receptor expression. Normal brain specimens, by contrast, stained positive for both DR5 and DcR1. Overexpression of DR5 under both transfection conditions resulted in cell death in all three cell lines. The previously seen resistance of U373 cells to TRAIL was not observed. Apoptotic cell death was confirmed using DNA fragmentation in T98G cell lines and fluorescent miscroscopy in all cell lines. The T98G cells stably transfected with bcl-2 before DR5 overexpression were protected from cell death. CONCLUSIONS: The authors conclude that DR5 represents a promising new approach to directly activating the intrinsic caspase pathway in glioma cells. The fact that TRAIL-resistant gliomas do not express decoy receptors suggests a mechanism of resistance unique from that proposed for normal tissues. The overexpression of DR5 induced apoptotic cell death in glioma cells without TRAIL and was able to overcome the resistance to TRAIL demonstrated in U373 cells. The Bcl-2 protects cells from DR5 by acting downstream of the receptor, most likely at the level of caspase activation.


Assuntos
Proteínas Reguladoras de Apoptose/biossíntese , Apoptose/fisiologia , Glioma/metabolismo , Glicoproteínas de Membrana/biossíntese , Fator de Necrose Tumoral alfa/biossíntese , Apoptose/genética , Proteínas Reguladoras de Apoptose/genética , Morte Celular/genética , Morte Celular/fisiologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Glioma/genética , Humanos , Glicoproteínas de Membrana/genética , Receptores do Fator de Necrose Tumoral/biossíntese , Receptores do Fator de Necrose Tumoral/genética , Ligante Indutor de Apoptose Relacionado a TNF , Fator de Necrose Tumoral alfa/genética
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