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1.
Pract Radiat Oncol ; 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32461036

RESUMO

Radiation therapy for mesothelioma remains challenging, as normal tissue toxicity limits the amount of radiation that can be safely delivered to the pleural surfaces, especially radiation dose to the contralateral lung. The physical properties of proton therapy result in better sparing of normal tissues when treating the pleura, both in the post-pneumonectomy setting and the lung-intact setting. Compared to photon radiation, there are dramatic reductions in dose to the contralateral lung, heart, liver, kidneys, and stomach. However, the tissue heterogeneity in the thorax, organ motion, and potential for changing anatomy during the treatment course all present challenges to optimal irradiation with protons. The clinical data underlying proton therapy in mesothelioma are reviewed here, including indications, advantages, and limitations. The Particle Therapy Co-operative Group (PTCOG) Thoracic Subcommittee task group provides specific guidelines for the use of proton therapy for mesothelioma. This consensus report can be used to guide clinical practice, insurance approval, and future research.

2.
Clin Cancer Res ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398326

RESUMO

PURPOSE: To quantitatively predict the impact of cardio-pulmonary dose on overall survival (OS) after radiotherapy for locally-advanced Non-Small Cell Lung Cancer. EXPERIMENTAL DESIGN: We used the NRG Oncology/RTOG 0617 dataset. The model building procedure was pre-registered on a public website. Patients were split between a training and a set-aside validation subset (N=306/131). The 191 candidate variables covered disease, patient, treatment, and dose-volume characteristics from multiple cardiopulmonary substructures (atria, lung, pericardium, and ventricles), including the minimum dose to the hottest x% volume (Dx%[Gy]), mean dose of the hottest x% (MOHx%[Gy]), and minimum, mean Mean[Gy], and maximum dose. The model building was based on Cox regression and given 191 candidate variables, a Bonferroni-corrected p-value threshold of 0.0003 was used to identify predictors. To reduce over-reliance on the most highly correlated variables, stepwise multivariable analysis (MVA) was repeated on 1000 bootstrapped replicates. Multivariable sets selected in ≥10% of replicates were fit to the training subset and then averaged to generate a final model. In the validation subset, discrimination was assessed using Harrell's c-index, and calibration was tested using risk group stratification. RESULTS: Four MVA models were identified on bootstrap. The averaged model included atria D45%[Gy], lung Mean[Gy], pericardium MOH55%[Gy], and ventricles MOH5%[Gy]. This model had excellent performance predicting OS in the validation subset (c=0.89). CONCLUSIONS: The risk of death due to cardio-pulmonary irradiation was accurately modeled, as demonstrated by predictions on the validation subset, and provides guidance on the delivery of safe thoracic radiotherapy.

3.
Radiother Oncol ; 147: 64-74, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32234612

RESUMO

BACKGROUND AND PURPOSE: IMPT improves normal tissue sparing compared to VMAT in treating oropharyngeal cancer (OPC). Our aim was to assess if this translates into clinical benefits. MATERIALS AND METHODS: OPC patients treated with definitive or adjuvant IMPT or VMAT from 2013 to 2018 were included. All underwent prospective assessment using patient-reported-outcomes (PROs) (EORTC-QLQ-H&N35) and provider-assessed toxicities (CTCAEv4.03). End-of-treatment and pretreatment scores were compared. PEG-tube use, hospitalization, and narcotic use were retrospectively collected. Statistical analysis used the Wilcoxon Rank-Sum Test with propensity matching for PROs/provider-assessed toxicities, and t-tests for other clinical outcomes. RESULTS: 46 IMPT and 259 VMAT patients were included; median follow-up was 12 months (IMPT) and 30 months (VMAT). Baseline characteristics were balanced except for age (p = 0.04, IMPT were older) and smoking (p < 0.01, 10.9% IMPT >20PYs, 29.3% VMAT). IMPT was associated with lower PEG placement (OR = 0.27; 95% CI: 0.12-0.59; p = 0.001) and less hospitalization ≤60 days post-RT (OR = 0.21; 95% CI:0.07-0.6, p < 0.001), with subgroup analysis revealing strongest benefits in patients treated definitively or with concomitant chemoradiotherapy (CRT). IMPT was associated with a relative risk reduction of 22.3% for end-of-treatment narcotic use. Patients reported reduced cough and dysgeusia with IMPT (p < 0.05); patients treated definitively or with CRT also reported feeling less ill, reduced feeding tube use, and better swallow. Provider-assessed toxicities demonstrated less pain and mucositis with IMPT, but more mucosal infection. CONCLUSION: IMPT is associated with improved PROs, reduced PEG-tube placement, hospitalization, and narcotic requirements. Mucositis, dysphagia, and pain were decreased with IMPT. Benefits were predominantly seen in patients treated definitively or with CRT.

4.
Oper Neurosurg (Hagerstown) ; 18(2): 136-144, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31250901

RESUMO

BACKGROUND: Surgical resection is typically cited as the optimal treatment of patients with Spetzler-Martin Grade I-II arteriovenous malformation (AVM). OBJECTIVE: To report our experience with single-fraction stereotactic radiosurgery (SRS) for Spetzler-Martin Grade I-II AVM. METHODS: A prospectively maintained registry was reviewed for patients with nonsyndromic Spetzler-Martin Grade I-II AVM having SRS from 1990 to 2011. Patients with <24 mo of follow-up or prior radiotherapy/SRS were excluded, resulting in a study population of 173 patients. Actuarial analysis was performed using the Kaplan-Meier method, and Cox proportional hazards modeling was performed with excellent outcomes (obliteration without new deficits) as the dependent variable. RESULTS: Median post-SRS follow-up was 68 mo (range, 24-275). AVM obliteration was achieved in 132 (76%) after initial SRS. Eleven additional patients achieved obliteration after repeat SRS for an overall obliteration rate of 83%. The rate of obliteration was 60% at 4 yr and 78% at 8 yr. Post-SRS hemorrhage occurred in 7 patients (4%), resulting in 3 minor deficits (2%) and 1 death (<1%). Radiation-induced complications occurred in 5 patients (3%), resulting in minor deficits only. One hundred and thirty-seven patients (79%) had excellent outcomes at last follow-up. CONCLUSION: SRS is a safe and effective treatment for patients with Spetzler-Martin Grade I-II AVM. Selection bias is likely a contributing factor to explain the superior outcomes generally noted in reported series of microsurgery for patients with low grade AVM.

5.
Neurosurgery ; 86(4): 557-564, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31140563

RESUMO

BACKGROUND: Patients with persistent or recurrent Cushing disease (CD) after prior transsphenoidal surgery require further treatment to reduce the disease's metabolic consequences. OBJECTIVE: To assess patient outcomes after stereotactic radiosurgery (SRS) for persistent or recurrent CD from adrenocorticotropin hormone (ACTH)-secreting pituitary adenomas and propose a management algorithm. METHODS: Retrospective review of 38 patients without prior radiation treatment having SRS for ACTH-secreting pituitary adenomas from 1990 to 2015. Favorable outcome was defined as biochemical remission and tumor growth control. Patients were evaluated separately if they underwent bilateral adrenalectomy (Adx). RESULTS: Twenty patients (53%) were treated with Adx and SRS (median margin dose, 25 Gy) and 18 patients (47%) received SRS alone (median margin dose, 22.5 Gy). Median follow-up after SRS was 76 mo. Of patients undergoing Adx, 18/20 (90%) had a favorable outcome. Two patients (10%) had tumor growth requiring additional treatment. A favorable outcome was achieved in 13/18 patients (72%) having SRS alone (median, 14 mo; interquartile range, 8-23). Five patients (28%) required additional treatment due to persistent hypercortisolemia (n = 4) or hypercortisolemia and tumor growth (n = 1). Favorable outcomes were more frequent in the Adx and SRS group at 1 yr (100% vs 33%; P < .001) and 3 yr (100% vs 62%; P < .01), but no different at 5 yr (88% vs 77%; P = .63). CONCLUSION: SRS was effective for patients with persistent or recurrent CD. Patients with mild to moderate CD can be safely managed with SRS alone; patients with severe CD should be considered for Adx with either concurrent SRS or SRS performed at a later date if tumor growth occurs.

7.
Mayo Clin Proc ; 94(9): 1814-1824, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31405750

RESUMO

OBJECTIVE: To determine whether N-acetylcysteine rinse was safe and could improve thickened secretions and dry mouth during and after radiotherapy. PATIENTS AND METHODS: We designed a prospective pilot double-blind, placebo-controlled randomized clinical trial (Alliance MC13C2). Adult patients (age ≥18 years) were enrolled if they underwent chemoradiotherapy (≥60 Gy). Patients initiated testing rinse within 3 days of starting radiotherapy. With swish-and-spit, they received 10% N-acetylcysteine (2500 mg daily) or placebo rinse solution 5 times daily during radiotherapy and 2 weeks postradiotherapy. The primary aim was to evaluate N-acetylcysteine in improvement of saliva viscosity with the Groningen Radiotherapy-Induced Xerostomia questionnaire. Secondary aims included evaluating xerostomia improvement by the same questionnaire and with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck-35 Questions survey and adverse-event profiles. The type I error rate was 20%. RESULTS: Thirty-two patients undergoing chemoradiotherapy were enrolled. Baseline characteristics were balanced for placebo (n=17) and N-acetylcysteine (n=15). N-acetylcysteine was better for improving sticky saliva (area under curve, P=.12). Scores of multiple secondary end points favored N-acetylcysteine, including sticky saliva daytime (P=.04), daytime and total xerostomia (both P=.02), pain (P=.18), and trouble with social eating (P=.15). Repeated measures models confirmed the findings. Taste was a major dissatisifer for N-acetylcysteine rinse; however, both testing rinses were safe and well tolerated overall. CONCLUSION: Our pilot data showed that N-acetylcysteine rinse was safe and provided strong evidence of potential efficacy for improving thickened saliva and xerostomia by patient-reported outcome. A confirmatory phase 3 trial is required. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02123511.


Assuntos
Acetilcisteína/uso terapêutico , Quimiorradioterapia/efeitos adversos , Neoplasias de Cabeça e Pescoço/terapia , Antissépticos Bucais/farmacologia , Mucosite/terapia , Xerostomia/tratamento farmacológico , Idoso , Quimiorradioterapia/métodos , Método Duplo-Cego , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/efeitos dos fármacos , Mucosite/etiologia , Medidas de Resultados Relatados pelo Paciente , Segurança do Paciente , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida , Valores de Referência , Medição de Risco , Resultado do Tratamento , Xerostomia/etiologia
8.
J Clin Oncol ; 37(22): 1909-1918, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31163012

RESUMO

PURPOSE: The purpose of this study was to determine if dose de-escalation from 60 to 66 Gy to 30 to 36 Gy of adjuvant radiotherapy (RT) for selected patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma could maintain historical rates for disease control while reducing toxicity and preserving swallow function and quality of life (QOL). PATIENTS AND METHODS: MC1273 was a single-arm phase II trial testing an aggressive course of RT de-escalation after surgery. Eligibility criteria included patients with p16-positive oropharyngeal squamous cell carcinoma, smoking history of 10 pack-years or less, and negative margins. Cohort A (intermediate risk) received 30 Gy delivered in 1.5-Gy fractions twice per day over 2 weeks along with 15 mg/m2 docetaxel once per week. Cohort B included patients with extranodal extension who received the same treatment plus a simultaneous integrated boost to nodal levels with extranodal extension to 36 Gy in 1.8-Gy fractions twice per day. The primary end point was locoregional tumor control at 2 years. Secondary end points included 2-year progression-free survival, overall survival, toxicity, swallow function, and patient-reported QOL. RESULTS: Accrual was from September 2013 to June 2016 (N = 80; cohort A, n = 37; cohort B, n = 43). Median follow-up was 36 months, with a minimum follow-up of 25 months. The 2-year locoregional tumor control rate was 96.2%, with progression-free survival of 91.1% and overall survival of 98.7%. Rates of grade 3 or worse toxicity at pre-RT and 1 and 2 years post-RT were 2.5%, 0%, and 0%. Swallowing function improved slightly between pre-RT and 12 months post-RT, with one patient requiring temporary feeding tube placement. CONCLUSION: Aggressive RT de-escalation resulted in locoregional tumor control rates comparable to historical controls, low toxicity, and little decrement in swallowing function or QOL.

9.
J Clin Oncol ; 37(15): 1316-1325, 2019 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-30943123

RESUMO

PURPOSE: Patients with centrally located early-stage non-small-cell lung cancer (NSCLC) are at a higher risk of toxicity from high-dose ablative radiotherapy. NRG Oncology/RTOG 0813 was a phase I/II study designed to determine the maximum tolerated dose (MTD), efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for centrally located NSCLC. MATERIALS AND METHODS: Medically inoperable patients with biopsy-proven, positron emission tomography-staged T1 to 2 (≤ 5 cm) N0M0 centrally located NSCLC were accrued into a dose-escalating, five-fraction SBRT schedule that ranged from 10 to 12 Gy/fraction (fx) delivered over 1.5 to 2 weeks. Dose-limiting toxicity (DLT) was defined as any treatment-related grade 3 or worse predefined toxicity that occurred within the first year. MTD was defined as the SBRT dose at which the probability of DLT was closest to 20% without exceeding it. RESULTS: One hundred twenty patients were accrued between February 2009 and September 2013. Patients were elderly, there were slightly more females, and the majority had a performance status of 0 to 1. Most cancers were T1 (65%) and squamous cell (45%). Organs closest to planning target volume/most at risk were the main bronchus and large vessels. Median follow-up was 37.9 months. Five patients experienced DLTs; MTD was 12.0 Gy/fx, which had a probability of a DLT of 7.2% (95% CI, 2.8% to 14.5%). Two-year rates for the 71 evaluable patients in the 11.5 and 12.0 Gy/fx cohorts were local control, 89.4% (90% CI, 81.6% to 97.4%) and 87.9% (90% CI, 78.8% to 97.0%); overall survival, 67.9% (95% CI, 50.4% to 80.3%) and 72.7% (95% CI, 54.1% to 84.8%); and progression-free survival, 52.2% (95% CI, 35.3% to 66.6%) and 54.5% (95% CI, 36.3% to 69.6%), respectively. CONCLUSION: The MTD for this study was 12.0 Gy/fx; it was associated with 7.2% DLTs and high rates of tumor control. Outcomes in this medically inoperable group of mostly elderly patients with comorbidities were comparable with that of patients with peripheral early-stage tumors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiocirurgia/efeitos adversos , Resultado do Tratamento
10.
Adv Radiat Oncol ; 4(2): 422-428, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31011688

RESUMO

Purpose: Previous studies suggest that stereotactic body radiation therapy (SBRT) is associated with higher toxicity rates for central lung tumors relative to peripheral tumors when using 3 fraction SBRT. The initial results from Radiation Therapy Oncology Group study 0813 suggest a safe toxicity profile of SBRT administered in 5 fractions for central non-small cell lung cancer (NSCLC). We reviewed our institutional data to evaluate the safety and efficacy of SBRT for central NSCLC. Methods and materials: We reviewed our prospectively collected SBRT database for patients with central NSCLC who received SBRT between 2008 and 2014. The most frequent dose and fractionations were 50 Gy in 5 fractions (59%) and 48 Gy in 4 fraction (30%). Local control (LC), regional control, metastasis-free survival, and overall survival were calculated using Kaplan-Meier estimates. The National Cancer Institute Common Terminal Criteria for Adverse Events were used for toxicity grading. Results: A total of 110 central lung tumors in 103 patients were included. The median age was 74 years (range, 40-95 years), and the median follow-up time of living patients was 50 months. The mean tumor size was 20 mm (range, 5-70 mm). The 5 year rate of LC, regional control, and distant control was 89%, 77%, and 82%, respectively. The median and 5-year overall survival were 3.5 years and 35%, respectively. No treatment variables were associated with tumor control or other clinical outcomes. A single patient experienced grade 3 radiation pneumonitis (0.97%). The rate of late toxicity grade ≥3 was 9.7% (grade 3, 7.7%; grade 4, 0.97%; grade 5, 0.97%) and included pneumonitis (3.9%), bronchial necrosis (2.9%), myocardial dysfunction (1.9%), and worsening heart failure (0.97%). Conclusions: SBRT for central NSCLC provides high rates of LC. Despite excellent LC, patients remain at risk for regional and distant failure. The rate of grade 3 pneumonitis was consistent with that of prior reports. We observed low rates of grade 4-5 toxicity potentially attributable to SBRT. Our results contribute to the growing body of data in support of the safety of SBRT for central NSCLC.

11.
Artigo em Inglês | MEDLINE | ID: mdl-30753469

RESUMO

OBJECTIVES: The aim of this study is to evaluate the efficacy of chest computed tomography (CT) to predict the pathological stage of thymic epithelial tumours (TET) using the recently introduced tumour, node and metastasis (TNM) staging with comparison to the modified Masaoka staging. METHODS: Preoperative chest CT examinations in cases of resected TET with sampled lymph nodes (2006-2016) were retrospectively reviewed by 2 thoracic radiologists and radiologically (r) staged using both staging systems. A thoracic pathologist reviewed all cases for the pathological (p) stage. Concordance between r-staging and p-staging was assessed by % agreement and unweighted kappa statistics. Associations between r-stage and p-stage with outcomes were assessed using the Cox proportional hazards regression. RESULTS: Sixty patients with TET were included (47 thymomas, 12 thymic carcinomas and 1 atypical carcinoid tumour). Sixteen patients (26.7%) had received neoadjuvant therapy. Fifty-four patients (90.0%) had complete resection. The overall agreement between the r-stage and p-stage was 66.7% (κ = 0.46) for TNM staging and 46.7% (κ = 0.30) for modified Masaoka staging. Agreement between r-assessment and p-assessment of the T, N and M components of the TNM stage was 61.7% (κ = 0.28), 86.7% (κ = 0.48) and 98.3% (κ = 0.88), respectively. CT overstaged 12 patients (20.0%) for TNM staging and 12 patients (20.0%) for modified Masaoka staging and understaged 8 (13.3%) and 20 (33.3%) patients for TNM staging modified Masaoka staging, respectively. The r-TNM staging accuracy was lower for patients with neoadjuvant therapy (50.0% with vs 72.7% without). During a median follow-up of 2.6 years (range 0.1-10.5 years), 12 patients had metastases and/or recurrence; 11 patients died (4 of disease). The r-TNM stage and modified Masaoka stage were associated with overall survival and progression-free survival (P < 0.001). CONCLUSIONS: Preoperative chest CT is able to accurately predict p-TNM stage in two-thirds of surgically resected TET, with an agreement between radiological staging and pathological staging superior to the modified Masaoka staging.

12.
Int J Radiat Oncol Biol Phys ; 103(3): 686-696, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30395904

RESUMO

PURPOSE: Chemoradiation (CRT) is an integral treatment modality for patients with locally advanced lung cancer. It has been hypothesized that current use of an angiotensin-converting enzyme inhibitor during CRT may be protective for treatment-related lung damage and pneumonitis. METHODS AND MATERIALS: We conducted a pilot, double-blind, placebo-controlled, randomized trial. Study-eligible patients receiving curative thoracic radiation therapy (RT) were randomly assigned to 20 mg of lisinopril or placebo once daily during and up to 3 months after RT. All patients received concurrent chemotherapy. The primary endpoint was adverse event profiling. Multiple patient-reported outcome (PRO) surveys, including the Lung Cancer Symptom Scale, Function Assessment of Cancer Therapy-Lung, and the European Organisation for Research and Treatment of Cancer Lung Cancer Questionnaire, were applied with a symptom experience questionnaire. Exploratory comparative statistics were used to detect differences between arms with χ2 and Kruskal-Wallis testing. RESULTS: Five institutions enrolled 23 patients. However, accrual was less than expected. Eleven and 12 patients were in the placebo and lisinopril arms, respectively (mean age, 63.5 years; male, 62%). Baseline characteristics were balanced. Eighteen patients (86%) were former or current smokers. The primary endpoint was met; neither arm had grade 3 or higher hypotension, acute kidney injury, allergic reaction (medication-induced cough), or anaphylaxis (medication-related angioedema). Few PRO measures suggested that compared with the placebo arm, patients receiving lisinopril had less cough, less shortness of breath, fewer symptoms from lung cancer, less dyspnea with both walking and climbing stairs, and better overall quality of life (for all, P < .05). CONCLUSIONS: Although underpowered because of low accrual, our results suggest that there was a clinical signal for safety-and possibly beneficial by limited PRO measures-in concurrently administering lisinopril during thoracic CRT to mitigate or prevent RT-induced pulmonary distress. Our results showed that a definitive, larger-scale, randomized phase 3 trial is needed in the future.


Assuntos
Quimiorradioterapia/métodos , Lisinopril/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Lesões por Radiação/prevenção & controle , Pneumonite por Radiação/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Quimiorradioterapia/efeitos adversos , Método Duplo-Cego , Dispneia/patologia , Feminino , Humanos , Pulmão/efeitos dos fármacos , Pulmão/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Projetos Piloto , Placebos , Qualidade de Vida , Lesões por Radiação/etiologia , Pneumonite por Radiação/etiologia , Radioterapia/métodos , Inquéritos e Questionários , Resultado do Tratamento
13.
Pract Radiat Oncol ; 9(1): 29-37, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30138746

RESUMO

PURPOSE: This study aimed to evaluate dose calculation accuracy for the Eclipse Analytical Anisotropic Algorithm (AAA) and Acuros XB algorithm for various lung tumor sizes and to investigate dosimetric changes associated with treatment of regressing tumors. METHODS AND MATERIALS: A water phantom with cylindrical cork inserts (lung surrogates) was fabricated. Large (202 cm3), medium (54 cm3), and small (3 cm3) solid water tumors were implanted within cork inserts. A plain cork insert was used to simulate a lung without a tumor. The cork inserts and tumors were cut along the long axis, and Gafchromic film was placed between the sections to measure dose distributions. Three-dimensional conformal plans were created using 6 MV and 10 MV beams, and volumetric modulated arc therapy plans were created using 6 MV beams for each tumor size. Doses were calculated using Eclipse AAA and Acuros XB. The measured and calculated dose distributions were compared for each tumor size and treatment algorithm. To simulate a regressing tumor, the original plans created for the large tumor were separately delivered to the phantom that contained a small, medium, or no tumor. The dosimetric effects were evaluated using gamma passing rates with a 2%/2 mm criterion and dose profile comparisons. RESULTS: Agreement between the measurements and AAA calculations decreased as tumor size decreased, but Acuros XB showed better agreement for all tumor sizes. The largest difference was observed for a 6 MV volumetric modulated arc therapy plan created to treat the smallest tumor. The gamma passing rate was 89.7% but that of Acuros was 99.5%. For the tumor regression evaluation, the gamma passing rates ranged from 53% to 99% for AAA. For Acuros XB, the gamma passing rates were >98% for all scenarios. CONCLUSION: Both AAA and Acuros XB calculated the dose accurately for the largest lung tumor. For the smallest and regressing tumors, Acuros XB more accurately modelled the dose distribution compared with AAA.


Assuntos
Neoplasias/patologia , Neoplasias/radioterapia , Órgãos em Risco/efeitos da radiação , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Humanos , Dosagem Radioterapêutica
14.
Mayo Clin Proc Innov Qual Outcomes ; 2(1): 40-48, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30225431

RESUMO

Objective: To examine disease control and survival after stereotactic body radiotherapy (SBRT) for medically inoperable, early-stage non-small cell lung cancer (NSCLC) and determine associations of pretreatment 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) maximum standardized uptake values (SUVmax), biologically effective dose, and mediastinal staging with disease control and survival outcomes. Patients and Methods: We retrospectively reviewed the cases of consecutive patients with FDG-PET-staged, medically inoperable NSCLC treated with SBRT at our institution between January 1, 2008, and August 4, 2014. Cumulative incidences of recurrence were estimated, accounting for the competing risk of death. Associations of SUVmax, biologically effective dose, and mediastinal staging with outcomes were evaluated using Cox proportional hazards regression models. Results: Among 282 patients, 2-year cumulative incidences of recurrence were 4.9% (95% CI, 2.6%-8.3%) for local, 9.8% (95% CI, 6.3%-14.2%) for nodal, 10.8% (95% CI, 7.0%-15.5%) for ipsilateral lung, 6.0% (3.3%-9.8%) for contralateral lung, 9.7% (95% CI, 6.3%-14.0%) for distant recurrence, and 26.1% (95% CI, 20.4%-32.0%) for any recurrence. The 2-year overall survival was 70.4% (95% CI, 64.5%-76.8%), and the 2-year disease-free survival was 51.2% (95% CI, 44.9%-58.5%). Risk of any recurrence was significantly higher for patients with higher SUVmax (hazard ratio [per each doubling], 1.29 [95% CI, 1.05-1.59]; P=.02). A similar association with SUVmax was observed when considering the composite outcome of any recurrence or death (hazard ratio, 1.23 [95% CI, 1.05-1.44]; P=.01). The SUVmax was not significantly associated with other outcomes (P≥0.69). Two-year cumulative incidences of local recurrence for patients receiving 48 Gy in 4 fractions, 54 Gy in 3 fractions, or 50 Gy in 5 fractions were 1.7% (95% CI, 0.3%-5.6%), 3.7% (95% CI, 0.7%-11.4%), and 15.3% (95% CI, 5.9%-28.9%), respectively (P=.02); this difference was independent of lesion size (P=.02). Conclusion: Disease control was excellent for patients who received SBRT for early-stage NSCLC, and this series represents the largest single-institution experience from the United States on SBRT for early-stage inoperable NSCLC. Higher pretreatment FDG-PET SUVmax was associated with increased risk of any recurrence, and the 50 Gy in 5 fractions dose prescription was associated with increased risk of local recurrence.

15.
Eur J Cardiothorac Surg ; 53(6): 1214-1222, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29293957

RESUMO

OBJECTIVES: The objective of this study is to build a novel prognostic nomogram in non-small-cell lung cancer (NSCLC) incorporating pre-treatment peripheral blood markers beyond known pathoclinical predictors. METHODS: We analysed 7158 patients with NSCLC diagnosed between 1 January 1997 and 31 December 2012 from a single institution with a uniform medical record and routine follow-up information. Besides common clinicopathological factors, we investigated the prognostic value of the neutrophil to lymphocyte ratio, monocytes and haemoglobin level in peripheral blood before treatment. Patients were randomly assigned to training (4772 patients, 66.7%) or validation cohorts (2386 patients, 33.3%). Cox proportional hazards models determined the effects of multiple factors on overall survival (OS). A nomogram was developed to predict median survival and 1-, 3-, 5- and 10-year OS for NSCLC. The performance of the nomogram was assessed by a concordance index and calibration curve. RESULTS: In the training cohort, the multivariate Cox model identified the neutrophil to lymphocyte ratio, monocytes and haemoglobin level before treatment as significant prognostic factors for OS independent of patient age, gender, smoking history of intensity and cessation, performance status, disease stage, tumour cell type and differentiation grade and therapies. All the significant prognostic variables were incorporated into a nomogram. In the validation cohort, the nomogram showed notable accuracy in predicting OS, with a concordance index of 0.81, and was well calibrated for predictions of OS. CONCLUSIONS: The proposed nomogram incorporating peripheral blood markers and known prognostic factors could accurately predict individualized survival probability of patients with NSCLC. It could be used in treatment planning and stratification in clinical trials.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Modelos Estatísticos , Nomogramas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Feminino , Hemoglobinas/análise , Humanos , Contagem de Leucócitos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto Jovem
16.
Am J Clin Oncol ; 41(4): 396-401, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-27100959

RESUMO

OBJECTIVES: The primary objective of NRG Oncology Radiation Therapy Oncology Group 0123 was to test the ability of the angiotensin-converting enzyme inhibitor captopril to alter the incidence of pulmonary damage after radiation therapy for lung cancer; secondary objectives included analyzing pulmonary cytokine expression, quality of life, and the long-term effects of captopril. MATERIALS AND METHODS: Eligible patients included stage II-IIIB non-small cell lung cancer, stage I central non-small cell lung cancer, or limited-stage small cell. Patients who met eligibility for randomization at the end of radiotherapy received either captopril or standard care for 1 year. The captopril was to be escalated to 50 mg three times a day. Primary endpoint was incidence of grade 2+ radiation-induced pulmonary toxicity in the first year. RESULTS: Eighty-one patients were accrued between June 2003 and August 2007. Given the low accrual rate, the study was closed early. No significant safety issues were encountered. Eight patients were ineligible for registration or withdrew consent before randomization and 40 patients were not randomized postradiation. Major reasons for nonrandomization included patients' refusal and physician preference. Of the 33 randomized patients, 20 were analyzable (13 observation, 7 captopril). The incidence of grade 2+ pulmonary toxicity attributable to radiation therapy was 23% (3/13) in the observation arm and 14% (1/7) in the captopril arm. CONCLUSIONS: Despite significant resources and multiple amendments, NRG Oncology Radiation Therapy Oncology Group 0123 was unable to test the hypothesis that captopril mitigates radiation-induced pulmonary toxicity. It did show the safety of such an approach and the use of newer angiotensin-converting enzyme inhibitors started during radiotherapy may solve the accrual problems.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Captopril/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Lesões por Radiação/tratamento farmacológico , Pneumonite por Radiação/tratamento farmacológico , Radioterapia Conformacional/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Qualidade de Vida , Lesões por Radiação/etiologia , Pneumonite por Radiação/etiologia
17.
Int J Radiat Oncol Biol Phys ; 99(5): 1173-1178, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-28939223

RESUMO

PURPOSE: To determine whether whole-brain radiation therapy (WBRT) is associated with improved overall survival among non-small cell lung cancer (NSCLC) patients with favorable prognoses at diagnosis. METHODS AND MATERIALS: In the N0574 trial, patients with 1 to 3 brain metastases were randomized to receive stereotactic radiosurgery (SRS) or SRS plus WBRT (SRS + WBRT), with a primary endpoint of cognitive deterioration. We calculated diagnosis-specific graded prognostic assessment (DS-GPA) scores for NSCLC patients and evaluated overall survival according to receipt of WBRT and DS-GPA score using 2 separate cut-points (≥2.0 vs <2.0 and ≥2.5 vs <2.5). RESULTS: A total of 126 NSCLC patients were included for analysis, with median follow-up of 14.2 months. Data for DS-GPA calculation were available for 86.3% of all enrolled NSCLC patients. Overall, 50.0% of patients had DS-GPA score ≥2.0, and 23.0% of patients had DS-GPA scores ≥2.5. The SRS and SRS + WBRT groups were well balanced with regard to prognostic factors. The median survival according to receipt of WBRT was 11.3 months (+WBRT) and 17.9 months (-WBRT) for patients with DS-GPA ≥2.0 (favorable prognoses, P=.63; hazard ratio 0.86; 95% confidence interval 0.47-1.59). Median survival was 3.7 months (+WBRT) and 6.6 months (-WBRT) for patients with DS-GPA <2.0 patients (unfavorable prognoses, P=.85; hazard ratio 0.95; 95% confidence interval 0.56-1.62). Outcomes according to the receipt of WBRT and DS-GPA remained similar utilizing DS-GPA ≥2.5 as a cutoff for favorable prognoses. There was no interaction between the continuum of the DS-GPA groups and WBRT on overall survival (P=.53). CONCLUSIONS: We observed no significant differences in survival according to receipt of WBRT in favorable-prognosis NSCLC patients. This study further supports the approach of SRS alone in the majority of patients with limited brain metastases.


Assuntos
Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Irradiação Craniana/mortalidade , Neoplasias Pulmonares , Radiocirurgia/mortalidade , Neoplasias Encefálicas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Terapia Combinada/métodos , Irradiação Craniana/métodos , Humanos , Neoplasias Pulmonares/patologia , Prognóstico , Radiocirurgia/métodos , Radioterapia Adjuvante/métodos , Radioterapia Adjuvante/mortalidade
18.
Pract Radiat Oncol ; 7(6): e531-e541, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28733185

RESUMO

OBJECTIVE: Pathologic complete response (pCR) following neoadjuvant chemoradiation (CRT) is associated with improved outcomes in stage III non-small cell lung cancer. Conflicting results exist regarding the value of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting pCR. This study evaluated the association between post-CRT FDG-PET and pCR using novel FDG-PET parameters. METHODS AND MATERIALS: This retrospective study included patients treated with CRT and resection. All underwent pre- and post-CRT FDG-PET imaging. Maximum standard uptake value (SUVmax), standard uptake ratio (SUR), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. RESULTS: In total, 44 patients were included for review. The majority had cT2 disease (59.0%). Median radiation dose was 60 Gy (45-70.2 Gy). Rate of pCR and near-pCR within the primary lesion was 29.5% and 45.5%, respectively. Average reduction in SUVmax was 9.2, whereas SUR normalized to mediastinum and liver showed mean reductions of 4.7 and 3.5, respectively. No association was found between pCR and either MTV or TLG. Reduction in SUVmax and SUR were significantly associated with increased rate of pCR (P ≤ .02). A threshold of >75% decrease in SUR-liver showed significant association with near-pCR (diagnostic odds ratio [DOR]: 8.3; P = .007). No correlation was found between nodal FDG-PET parameters and nodal pCR. CONCLUSIONS: Our results indicate SUV and SUR have utility in predicting pCR after neoadjuvant CRT. SUR parameters trended toward higher DORs, suggesting improved predictive utility compared with SUVmax. Notably, no association was found with nodal pCR. Furthermore, MTV and TLG changes were not predictive, potentially resulting from inflammation after full-dose radiation, but this warrants further investigation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Metástase Linfática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Análise de Sobrevida , Resultado do Tratamento
19.
Adv Radiat Oncol ; 2(1): 12-18, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28740911

RESUMO

PURPOSE: For patients with stage III (N2) non-small cell lung cancer (NSCLC) treated with surgical resection, postoperative chemotherapy improves overall survival (OS), but the role of postoperative radiation therapy (PORT) is controversial. The purpose of this study was to evaluate risk factors for local-regional recurrence and to evaluate the impact of PORT on local-regional control (LRC) and OS in a modern series of patients with surgically resected stage III (N2) NSCLC. METHODS AND MATERIALS: A retrospective review was performed of patients with Stage III (N2) NSCLC who underwent curative intent resection at our institution between February 1999 and January 2012. OS, LRC, and metastasis-free survival were estimated from the date of surgery using the Kaplan Meier method. RESULTS: A total of 71 patients were included in the study. Patient median age was 63 years. Histology was adenocarcinoma in 69% of patients. Pretreatment positron emission tomography/computed tomography staging was performed for 90% of patients, and preoperative chemotherapy was administered in 23%. The rate of R0 resection was 96%. Forty-one patients (58%) received PORT and the median PORT dose was 50 Gy (range, 41.4-60 Gy). The median follow-up time for living patients was 5.0 years. Five-year OS for all patients was 66%. OS at 5 years for patients who received PORT compared with patients who did not receive PORT was 71% versus 60%, respectively (hazard ratio [HR], 0.61; 95% CI, 0.30-1.44; P = .28). LRC at 5 years for patients who received PORT compared with patients who did not receive PORT was 89% versus 76%, respectively (HR, 0.44; 95% CI, 0.13-1.45; P = .17). Factors associated with decreased LRC were male sex (P = .011) and primary tumor (pT) stage (pT3/4 vs. pT1/2, P = .006). Metastasis-free survival at 5 years for patients who received PORT compared with those who did not receive PORT was 62% versus 63%, respectively (HR, 1.07; 95% CI, 0.51-2.40; P = .86). CONCLUSIONS: In this modern series of patients with resected stage III (N2) NSCLC, patients who received PORT had higher rates of OS and LRC, but these differences were not statistically significant.

20.
J Thorac Oncol ; 12(9): 1398-1402, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28583587

RESUMO

INTRODUCTION: Multifocal lung cancer is an increasingly common clinical scenario, but there is lack of high-level evidence for its optimal treatment. Thus, we surveyed members of the interdisciplinary International Association for the Study of Lung Cancer on their therapeutic approaches and analyzed the resultant practice patterns. METHODS: We described the clinical scenario of an otherwise healthy 60-year-old man with bilateral pulmonary nodules and asked the 6373 members of the International Association for the Study of Lung Cancer whether they would recommend surgery, and if so, the extent of surgery. We also asked what other measures would be recommended to complete the staging and whether radiation therapy or chemotherapy would be suggested. RESULTS: We received 221 responses (response rate 3.5%) from multiple specialists. Most respondents (140 [63%]) recommended surgery for this scenario. Surgeons were significantly more likely to recommend surgery than were those in other specialties. Of those who recommended surgery, most would obtain a PET/CT scan to rule out distant metastases and a magnetic resonance imaging scan to rule out brain metastases; but in the absence of radiographic lymph node involvement, most would not stage the mediastinum by bronchoscopy or mediastinoscopy before resection. When surgery was not recommended or declined, respondents commonly recommended radiation. CONCLUSIONS: This survey suggests that therapeutic recommendations for multifocal lung cancer are influenced to a large extent by physicians' specialty training, probably because of the lack of high-level evidence for its standard treatment. Ongoing systematic and multidisciplinary approaches with robust short-term and long-term patient outcomes may improve the quality of evidence for the optimal management of this clinical entity.


Assuntos
Neoplasias Pulmonares/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Inquéritos e Questionários
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