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1.
Int J Part Ther ; 8(2): 17-27, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722808

RESUMO

Purpose: To assess possible differences in radiation-induced lymphocyte depletion for esophageal cancer patients being treated with the following 3 treatment modalities: intensity-modulated radiation therapy (IMRT), passive scattering proton therapy (PSPT), and intensity-modulated proton therapy (IMPT). Methods and Materials: We used 2 prediction models to estimate lymphocyte depletion based on dose distributions. Model I used a piecewise linear relationship between lymphocyte survival and voxel-by-voxel dose. Model II assumes that lymphocytes deplete exponentially as a function of total delivered dose. The models can be fitted using the weekly absolute lymphocyte counts measurements collected throughout treatment. We randomly selected 45 esophageal cancer patients treated with IMRT, PSPT, or IMPT at our institution (15 per modality) to demonstrate the fitness of the 2 models. A different group of 10 esophageal cancer patients who had received PSPT were included in this study of in silico simulations of multiple modalities. One IMRT and one IMPT plan were created, using our standards of practice for each modality, as competing plans to the existing PSPT plan for each patient. We fitted the models by PSPT plans used in treatment and predicted absolute lymphocyte counts for IMRT and IMPT plans. Results: Model validation on each modality group of patients showed good agreement between measured and predicted absolute lymphocyte counts nadirs with mean squared errors from 0.003 to 0.023 among the modalities and models. In the simulation study of IMRT and IMPT on the 10 PSPT patients, the average predicted absolute lymphocyte count (ALC) nadirs were 0.27, 0.35, and 0.37 K/µL after IMRT, PSPT, and IMPT treatments using Model I, respectively, and 0.14, 0.22, and 0.33 K/µL using Model II. Conclusions: Proton plans carried a lower predicted risk of lymphopenia after the treatment course than did photon plans. Moreover, IMPT plans outperformed PSPT in terms of predicted lymphocyte preservation.

2.
J Geriatr Oncol ; 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34756496

RESUMO

PURPOSE: Expected toxicity from chemoradiation (CRT) is an important factor in treatment decisions but is poorly understood in older adults with lower gastrointestinal (GI) malignancies. Our objective was to compare acute adverse events (AAEs) of older and younger adults with lower GI malignancies treated on NRG studies. METHODS: Data from 6 NRG trials, testing combined modality therapy in patients with anal or rectal cancer, were used to test the hypothesis that older age was associated with increased AAEs. AAEs and compliance with protocol-directed therapy were compared between patients aged ≥70 and < 70. Categorical variables were compared across age groups using the chi-square test. The association of age on AAEs was evaluated using a covariate-adjusted logistic regression model, with odds ratio (OR) reported. To adjust for multiple comparisons, a p-value <0.01 was considered statistically significant. RESULTS: There were 2525 patients, including 380 patients ≥70 years old (15%) evaluable. Older patients were more likely to have worse baseline performance status (PS 1 or 2) (23% vs. 16%, p = 0.001), but otherwise baseline characteristics were similar. Older patients were less likely to complete their chemotherapy (78% vs. 87%, p < 0.001), but had similar RT duration. On univariate analysis, older patients were more likely to experience grade ≥ 3 GI AAEs (36% vs. 23%, p < 0.001), and less likely to experience grade ≥ 3 skin AAEs (8% vs. 14%, p = 0.002). On multivariable analysis, older age was associated with grade ≥ 3 GI AAE (OR 1.93, 95% CI: 1.52, 2.47, p < 0.001) after adjusting for sex, race, PS, and disease site. CONCLUSIONS: Older patients with lower GI cancers who underwent CRT were less likely to complete chemotherapy and had higher rates of grade 3+ GI AAEs. These results can be used to counsel older adults prior to treatment and manage expected toxicities throughout pelvic CRT.

4.
Adv Radiat Oncol ; 6(1): 100545, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33665481

RESUMO

Purpose: Radiation therapy (RT)-induced lymphopenia (RIL) is linked with inferior survival in esophageal and pancreatic cancers. Previous work has demonstrated a correlation between spleen dose and RIL risk. The present study correlates spleen dose-volume parameters with fractional lymphocyte loss rate (FLL) and total percent change in absolute lymphocyte count (%ΔALC) and suggests spleen dose constraints to reduce RIL risk. Methods and Materials: This registry-based study included 140 patients who underwent RT for pancreatic (n = 67), gastroesophageal (n = 61), or biliary tract (n = 12) adenocarcinoma. Patient-specific parameters of lymphocyte loss kinetics, including FLL and %ΔALC, were calculated based on serial ALCs obtained during RT. Spearman's rho was used to correlate spleen dose-volume parameters with %ΔALC, end-treatment ALC, and FLL. Multivariable logistic regression was used to identify predictors of ≥grade 3 and grade 4 RIL. Results: Spleen dose-volume parameters, including mean spleen dose (MSD), all correlated with %ΔALC, end-treatment ALC, and FLL. Controlling for baseline ALC and planning target volume (PTV), an increase in any spleen dose-volume parameter increased the odds of developing ≥grade 3 lymphopenia. Each 1-Gy increase in MSD increased the odds of ≥grade 3 RIL by 18.6%, and each 100-cm3 increase in PTV increased the odds of ≥grade 3 lymphopenia by 20%. Patients with baseline ALC < 1500 cells/µL had a high risk of ≥grade 3 RIL regardless of MSD or PTV. FLL was an equally good predictor of ≥grade 3 lymphopenia as any spleen dose-volume parameter. Conclusions: In patients undergoing RT for upper abdominal malignancies, higher spleen dose is associated with higher per-fraction lymphocyte loss rates, higher total %ΔALC, and increased odds of severe lymphopenia. Spleen dose constraints should be individualized based on baseline ALC and PTV size to minimize RIL risk, although our findings require validation in larger, ideally prospective data sets.

5.
Ann Surg Oncol ; 28(5): 2438-2446, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33523364

RESUMO

AIMS: National studies have demonstrated disparities in the treatment and survival of pancreatic cancer patients based on socioeconomic status (SES). This study aimed to identify specific differences in perioperative management and outcomes based on patient SES and to study the role of a multidisciplinary clinic (MDC) in mitigating any variations. METHODS: The study analyzed patients undergoing pancreaticoduodenectomy for pancreatic ductal adenocarcinoma in a large hospital system. The patients were categorized into groups of high and low SES and whether they were managed by the authors' pancreatic cancer MDC or not. The study compared differences in disease characteristics, receipt of multimodality therapy, perioperative outcomes, and recurrence-free and overall survival. RESULTS: Of the 162 low-SES patients and 119 high-SES patients, 54% were managed in the MDC. Outside the MDC, low-SES patients were less likely to receive neoadjuvant chemotherapy and had less minimally invasive surgery, a longer OR time, less enhanced recovery participation, and more major complications (p < 0.05). No SES disparities were observed among the MDC patients. Despite similar tumor characteristics, the low-SES patients had inferior median overall survival (21 vs 32 months; p = 0.005), but the MDC appeared to eliminate this disparity. Low SES correlated with inferior survival for the non-MDC patients (17 vs 32 months; p < 0.001), but not for the MDC patients (24 vs 25 months; p = 0.33). These findings persisted in the multivariable analysis. CONCLUSION: A pancreatic cancer MDC standardizes treatment decisions, eliminates disparities in surgical outcomes, and improves survival for low-SES patients.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/cirurgia , Disparidades em Assistência à Saúde , Humanos , Recidiva Local de Neoplasia , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Classe Social
6.
Ann Surg Oncol ; 28(7): 3779-3788, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33231769

RESUMO

BACKGROUND: Neoadjuvant therapy is increasingly used for patients with pancreatic ductal adenocarcinoma (PDAC). It is unknown whether neoadjuvant chemoradiotherapy is more effective than chemotherapy (NCRT vs. NAC). We aim to compare pathological and survival outcomes of NCRT and NAC in patients with PDAC. PATIENTS AND METHODS: Single-center analysis of PDAC patients treated with NCRT or NAC followed by resection between December 2008 and December 2018 was performed. Average treatment effect (ATE) was estimated after case-control matching using Mahalanobis distance nearest-neighbor matching. Inverse probability weighted estimates (IPWE)-based ATE was estimated for disease-free survival (DFS) and overall survival (OS). RESULTS: Among the 418 patients (mean age 66.8 years, 51% female) included in the study, 327 received NAC and 91 received NCRT. NCRT patients had higher rates of locally advanced disease, number of neoadjuvant chemotherapy cycles, more chemotherapy regimen crossover (gemcitabine and 5-FU based), and were more likely to undergo open surgical procedures and/or vascular resection (all p < 0.05). After matched analysis, NCRT was associated with a significant reduction in lymph node positive disease [ATE = (-)0.24, p = 0.007] and lymphovascular invasion [ATE = (-)0.20, p = 0.02]. While NCRT was associated with significantly improved DFS by 9.5 months (p = 0.006), it did not affect OS by IPWE-based ATE after adjusting for adjuvant therapy (ATE = 5.5 months; p = 0.32). CONCLUSION: Compared with NAC alone, NCRT is associated with improved pathologic surrogates and disease-free survival, but not overall survival in patients with PDAC.


Assuntos
Terapia Neoadjuvante , Neoplasias Pancreáticas , Idoso , Quimiorradioterapia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias Pancreáticas/terapia , Estudos Retrospectivos
8.
Future Oncol ; 16(32): 2635-2643, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32976060

RESUMO

Aim: To identify demographic predictors of patients who miss oncology follow-up, considering that missed follow-up has not been well studies in cancer patients. Methods: Patients with solid tumors diagnosed from 2007 to 2016 were analyzed (n = 16,080). Univariate and multivariable logistic regression models were constructed to examine predictors of missed follow-up. Results: Our study revealed that 21.2% of patients missed ≥1 follow-up appointment. African-American race (odds ratio [OR] 1.33; 95% CI: 1.17-1.51), Medicaid insurance (OR 1.59; 1.36-1.87), no insurance (OR 1.66; 1.32-2.10) and rural residence (OR 1.78; 1.49-2.13) were associated with missed follow-up. Conclusion: Many cancer patients miss follow-up, and inadequate follow-up may influence cancer outcomes. Further research is needed on how to address disparities in follow-up care in high-risk patients.


Assuntos
Neoplasias/epidemiologia , Grupos de Populações Continentais/estatística & dados numéricos , Demografia , Feminino , Pesquisas sobre Serviços de Saúde , Disparidades em Assistência à Saúde , Humanos , Masculino , Medicaid , Neoplasias/diagnóstico , Neoplasias/terapia , Estados Unidos
9.
Rep Pract Oncol Radiother ; 25(4): 698-700, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32684855

RESUMO

Introduction: For patients with brain metastases, palliative radiation therapy (RT) has long been a standard of care for improving quality of life and optimizing intracranial disease control. The duration of time between completion of palliative RT and patient death has rarely been evaluated. Methods: A compilation of two prospective institutional databases encompassing April 2015 through December 2018 was used to identify patients who received palliative intracranial radiation therapy. A multivariate logistic regression model characterized patients adjusting for age, sex, admission status (inpatient versus outpatient), Karnofsky Performance Status (KPS), and radiation therapy indication. Results: 136 consecutive patients received intracranial palliative radiation therapy. Patients with baseline KPS <70 (OR = 2.2; 95%CI = 1.6-3.1; p < 0.0001) were significantly more likely to die within 30 days of treatment. Intracranial palliative radiation therapy was most commonly delivered to provide local control (66% of patients) or alleviate neurologic symptoms (32% of patients), and was most commonly delivered via whole brain radiation therapy in 10 fractions to 30 Gy (38% of patients). Of the 42 patients who died within 30 days of RT, 31 (74%) received at least 10 fractions. Conclusions: Our findings indicate that baseline KPS <70 is independently predictive of death within 30 days of palliative intracranial RT, and that a large majority of patients who died within 30 days received at least 10 fractions. These results indicate that for poor performance status patients requiring palliative intracranial radiation, hypofractionated RT courses should be strongly considered.

10.
Rep Pract Oncol Radiother ; 25(4): 500-506, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32477016

RESUMO

Introduction: Up to 20% of patients with brain metastases treated with immune checkpoint inhibitor (ICI) therapy and concomitant stereotactic radiosurgery (SRS) suffer from symptomatic radiation necrosis. The goal of this study is to evaluate Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI) on six-month symptomatic radiation necrosis rates. Methods: This study is a prospective single arm Phase I pilot study which will recruit patients with brain metastases receiving ICI delivered within 30 days before SRS. All patients will be treated with RADREMI dosing, which involves SRS doses of 18 Gy for 0-2 cm lesions, 14 Gy for 2.1-3 cm lesions, and 12 Gy for 3.1-4 cm lesions. All patients will be monitored for six-month symptomatic radiation necrosis (defined as a six-month rate of clinical symptomatology requiring steroid administration and/or operative intervention concomitant with imaging findings consistent with radiation necrosis) and six-month local control. We expect that RADREMI dosing will significantly reduce the symptomatic radiation necrosis rate of concomitant SRS + ICI without significantly sacrificing the local control obtained by the present RTOG 90-05 SRS dosing schema. Local control will be defined according to the Response Assessment in Neuro-Oncology (RANO) criteria. Discussion: This study is the first prospective trial to investigate the safety of dose-reduced SRS in treatment of brain metastases with concomitant ICI. The findings should provide fertile soil for future multi-institutional collaborative efficacy trials of RADREMI dosing for this patient population. Trial Registration: Clinicaltrials.gov identifier: NCT04047602 (registration date: July 25, 2019).

11.
Med Dosim ; 45(2): 117-120, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31439270

RESUMO

INTRODUCTION: Radiation planning approaches for liver radiation often do not consider the regional variation that can exist in liver function. This study dosimetrically compares functional liver image-guided hepatic therapy (FLIGHT) to standard stereotactic body radiation therapy (SBRT) plans. In the FLIGHT plans, functional data from hepatobiliary iminodiacetic acid (HIDA) single photon emission computed tomography (SPECT) scans serve as a road map to guide beam arrangement. While meeting the same target volume coverage, plans are optimized to reduce dose to high-functioning liver. MATERIALS AND METHODS: The study included 10 patients with hepatocellular carcinoma (HCC) with baseline HIDA SPECT imaging. Standard SBRT plans which did not systematically incorporate these scans had previously been completed on all 10 plans. Retrospectively, FLIGHT plans were created based on the use of contours of relative liver function from the HIDA SPECT as avoidance structures. Resulting dose to each relative functional liver structure was examined and compared qualitatively and using Wilcoxin rank-sum tests. Target coverage, doses to organs at risk (OARs), conformity index (CI), and gradient index (GI) were also evaluated. RESULTS: While maintaining the same target coverage, FLIGHT plans reduced the mean dose to the high functioning liver by a median of 3.0 Gy (range 0.7 to 4.6 Gy), which represented a 31.4% mean reduction compared to standard planning. FLIGHT plans reduced the volume of high functioning liver receiving 15 Gy by a mean of 59.3 cc (range 7 to 170 cc), for a mean reduction of 41.9%. The mean dose to areas of liver function defined by 25% to 100% and 50% to 100% maximum was reduced with FLIGHT from 10.5 Gy to 8.5 Gy and from 10.5 Gy to 7.5 Gy, respectively (p < 0.005 for both comparisons). The FLIGHT plans' mean CI and GI did not differ significantly from the standard plans' (p = 0.721 and 0.169, respectively). CONCLUSION: FLIGHT SBRT allows for field design and plan optimization individualized to a patient's baseline regional liver function to maximize hepatic functional reserve. This personalized approach is achieved without compromising target coverage or OAR sparing.


Assuntos
Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Radiocirurgia , Planejamento da Radioterapia Assistida por Computador , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Feminino , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade
12.
Clin Cancer Res ; 26(1): 282-289, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31471311

RESUMO

PURPOSE: We recently reported that indoleamine 2, 3-dioxygenase (IDO) activity is significantly correlated with more distant metastasis and worse survival. The present study examined whether radiotherapy (RT) dose fractionation correlates with IDO-mediated immune activity in patients with early-stage NSCLC.Methods: Patients with newly diagnosed stage I-II NSCLC treated with either conventionally fractionated 3-dimensional conformal radiotherapy (3DCRT) or stereotactic body radiotherapy (SBRT) were analyzed. Levels of two key molecules associated with the IDO immune checkpoint, serum kynurenine and the kynurenine:tryptophan ratio (K:T ratio), were measured at pre-RT, during-RT, and 3-month post-RT. The relationship between disease control outcomes [overall survival (OS), progression free survival, and local/regional/distant failure rates] and absolute levels of these markers, as well as dynamic changes in their levels during RT, was studied. RESULTS: Fifty-six patients (SBRT = 28, 3DCRT = 28) with early-stage NSCLC were studied. In all patients, higher kynurenine post-RT was significantly associated with worse OS ([HR, 1.25; 95% confidence interval (CI), 1.01-1.55; P = 0.044). No statistically significant differences in absolute kynurenine levels or the K:T ratio were observed in patients treated with 3DCRT or SBRT at any of the three time points. However, the absolute kynurenine levels rose significantly more post-RT in the 3DCRT patients with a median increase 0.721 ng/mL, compared to that of SBRT patients (0.115 ng/mL); P = 0.022. CONCLUSIONS: This study validated that elevated IDO activity correlated with worse survival outcomes in patients with early-stage NSCLC treated with definitive RT. Hypofractionated SBRT may have less immunosuppressive effect than 3DCRT, as measured by IDO.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Neoplasias Pulmonares/mortalidade , Radiocirurgia/métodos , Radioterapia Conformacional/métodos , Idoso , Biomarcadores Tumorais/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Fracionamento da Dose de Radiação , Feminino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Cinurenina/sangue , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/radioterapia , Masculino , Estadiamento de Neoplasias , Taxa de Sobrevida , Triptofano/sangue
13.
Radiat Res ; 193(1): 73-81, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675264

RESUMO

Radiation-induced lymphopenia (RIL) is associated with worse survival in patients with solid tumors, as well as lower response rates to checkpoint inhibitors. While single-fraction total-body irradiation is known to result in exponential decreases in the absolute lymphocyte count (ALC), the kinetics of lymphocyte loss after focal fractionated exposures have not previously been characterized. In the current study, lymphocyte loss kinetics was analyzed among patients undergoing focal fractionated radiotherapy for clinical indications. This registry-based study included 419 patients who received either total-body irradiation (TBI; n = 30), stereotactic body radiation therapy (SBRT; n = 73) or conventionally fractionated chemoradiation therapy (CFRT; n = 316). For each patient, serial ALCs were plotted against radiotherapy fraction number. The initial three weeks of treatment for CFRT patients and the entirety of treatment for SBRT and TBI patients were fit to exponential decay in the form ALC(x) = ae-bx, where ALC(x) is the ALC after x fractions. From those fits, fractional lymphocyte loss (FLL) was calculated as FLL = (1 - e-b) * 100, and multivariable regression was performed to identify significant correlates of FLL. Median linearized R2 when fitting the initial fractions was 0.98, 0.93 and 0.97 for patients receiving TBI, SBRT and CFRT, respectively. In CFRT patients, apparent ALC loss rate slowed after week 3. Fitting ALC loss over the entire CFRT course therefore required the addition of a constant term, "c". For TBI and SBRT patients, treatment ended during the pure exponential decay phase. Initial FLL varied significantly with treatment technique. Mean FLL was 35.5%, 24.3% and 10.77% for patients receiving TBI, SBRT and CFRT, respectively (P < 0.001). Significant correlates of FLL varied by site and included field size, dose per fraction, mean spleen dose, chemotherapy backbone and age. Finally, total percentage ALC loss during radiotherapy was highly correlated with FLL (P < 0.001). Lymphocyte depletion kinetics during the initial phase of fractionated radiotherapy are characterized by pure exponential decay. Initial FLL is strongly correlated with radiotherapy planning parameters and total percentage ALC loss. The two groups with the highest FLL received no concurrent chemotherapy, suggesting that ALC loss can be a consequence of radiotherapy alone. This work may assist in selecting patients for adaptive radiotherapy approaches to mitigate RIL risk.


Assuntos
Quimiorradioterapia/efeitos adversos , Linfócitos/citologia , Linfócitos/efeitos da radiação , Radiocirurgia/efeitos adversos , Adulto , Idoso , Contagem de Células , Fracionamento da Dose de Radiação , Feminino , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Nat Rev Clin Oncol ; 16(12): 729-745, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31243334

RESUMO

Immunotherapy, specifically the introduction of immune checkpoint inhibitors, has transformed the treatment of cancer, enabling long-term tumour control even in individuals with advanced-stage disease. Unfortunately, only a small subset of patients show a response to currently available immunotherapies. Despite a growing consensus that combining immune checkpoint inhibitors with radiotherapy can increase response rates, this approach might be limited by the development of persistent radiation-induced immunosuppression. The ultimate goal of combining immunotherapy with radiotherapy is to induce a shift from an ineffective, pre-existing immune response to a long-lasting, therapy-induced immune response at all sites of disease. To achieve this goal and enable the adaptation and monitoring of individualized treatment approaches, assessment of the dynamic changes in the immune system at the patient level is essential. In this Review, we summarize the available clinical data, including forthcoming methods to assess the immune response to radiotherapy at the patient level, ranging from serum biomarkers to imaging techniques that enable investigation of immune cell dynamics in patients. Furthermore, we discuss modelling approaches that have been developed to predict the interaction of immunotherapy with radiotherapy, and highlight how they could be combined with biomarkers of antitumour immunity to optimize radiotherapy regimens and maximize their synergy with immunotherapy.


Assuntos
Sistema Imunitário/efeitos da radiação , Imunoterapia , Neoplasias/imunologia , Neoplasias/terapia , Radioterapia , Terapia Combinada/métodos , Humanos , Sistema Imunitário/fisiologia , Imunoterapia/métodos , Neoplasias/patologia , Medicina de Precisão/métodos , Radioterapia/métodos
16.
Cancer Invest ; 37(2): 67-72, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30873889

RESUMO

There has been controversy about the presence and potential role of aquaporin-4 (AQP4) in glioblastoma (GBM). We analyzed tissue from 22 patients with newly-diagnosed GBM as well as matching tissue from 17 of these cases who underwent repeat resection for suspected recurrence and performed immunohistochemical analysis for AQP-4 expression. While some degree of AQP4 expression was detected in all 22 cases (39 samples), there was no clear relationship between staining pattern and disease status (active versus inactive GBM) between baseline and time of repeat biopsy. In addition, there was no clear relationship between AQP4 expression and degree of edema.


Assuntos
Aquaporina 4/metabolismo , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Adulto , Idoso , Biópsia , Neoplasias Encefálicas/patologia , Quimiorradioterapia/métodos , Progressão da Doença , Edema/metabolismo , Edema/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Glioblastoma/patologia , Glioma/metabolismo , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos
18.
Clin Lung Cancer ; 20(3): 186-193.e3, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30711394

RESUMO

INTRODUCTION/BACKGROUND: Many patients with early stage non-small-cell lung cancer (ES-NSCLC) undergoing stereotactic body radiation therapy (SBRT) develop metastases, which is associated with poor outcomes. We sought to identify factors predictive of metastases after lung SBRT and created a risk stratification tool. MATERIALS AND METHODS: We included 363 patients with ES-NSCLC who received SBRT; the median follow-up was 5.8 years. The following patient and tumor factors were retrospectively analyzed for their association with metastases (defined as nodal and/or distant failure): gender; age; lobe involved; centrality; previous NSCLC; smoking status; gross tumor volume (GTV); T-stage; histology; dose; minimum, maximum, and mean GTV dose; and parenchymal lung failure. A metastasis risk-score linear-model using beta coefficients from a multivariate Cox model was built. RESULTS: A total of 111 (27.3%) of 406 lesions metastasized. GTV and dose were significantly associated with metastases on univariate and multivariate Cox proportional hazards modeling (P < .001 and hazard ratio [HR], 1.02 per mL; P < .05 and HR, 0.99 per Gy, respectively). Histology, T-stage, centrality, lung parenchymal failures, and previous NSCLC were not associated with development of metastasis. A metastasis risk-score model using GTV and prescription dose was built: risk score = (0.01611 × GTV) - (0.00525 × dose [BED10]). Two risk-score cutoffs separating the cohort into low-, medium-, and high-risk subgroups were examined. The risk score identified significant differences in time to metastases between low-, medium-, and high-risk patients (P < .001), with 3-year estimates of 81.1%, 63.8%, and 38%, respectively. CONCLUSION: GTV and radiation dose are associated with time to metastasis and may be used to identify patients at higher risk of metastasis after lung SBRT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Progressão da Doença , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento , Carga Tumoral
19.
Adv Radiat Oncol ; 3(4): 512-519, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30370350

RESUMO

Purpose: Radiation-induced lymphopenia (RIL) is the result of direct toxicity to circulating lymphocytes as they traverse the irradiated field, occurs in 40% to 70% of patients who undergo conventional external beam radiation therapy, and is associated with worse outcomes in multiple solid tumors. As immunotherapy strategies evolve, a better understanding of radiation's effects on the immune system is needed in order to develop rational methods of combining RT with immunotherapy. Methods and materials: This paper is a review of the available literature on the clinical significance and dosimetric predictors of radiation-induced toxicity to the immune system. Results: An association between severe RIL and inferior survival has been described in multiple solid tumors, including glioma, lung cancer, and pancreatic cancer. RIL risk is correlated with field size, dose per fraction, and fraction number. SBRT and proton therapy techniques are associated with lower RIL risk. Conclusions: The immune system should be considered an organ at risk during RT, and absolute lymphocyte count is an important biomarker of RT-induced immunotoxicity. Radiation dose and technique affect the risk and severity of RIL. Further research is needed to accurately characterize RT-induced immunotoxicity and develop strategies to prevent or mitigate this clinically significant side effect.

20.
Pract Radiat Oncol ; 8(6): 429-436, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29907502

RESUMO

PURPOSE: Hepatobiliary iminodiacetic acid (HIDA) scans provide global and regional assessments of liver function that can serve as a road map for functional avoidance in stereotactic body radiation therapy (SBRT) planning. Functional liver image guided hepatic therapy (FLIGHT), an innovative planning technique, is described and compared with standard planning using functional dose-volume histograms. Thresholds predicting for decompensation during follow up are evaluated. METHODS AND MATERIALS: We studied 17 patients who underwent HIDA scans before SBRT. All SBRT cases were replanned using FLIGHT. The following dosimetric endpoints were compared for FLIGHT versus standard SBRT planning: functional residual capacity <15 Gy (FRC15HIDA), mean liver dose (MLD), equivalent uniform dose (EUD), and functional EUD (FEUD). Receiver operating characteristics curves were used to evaluate whether baseline HIDA values, standard cirrhosis scoring, and/or dosimetric data predicted clinical decompensation. RESULTS: Compared with standard planning, FLIGHT significantly improved FRC15HIDA (mean improvement: 5.3%) as well as MLD, EUD, and FEUD (P < .05). Considerable interindividual variations in the extent of benefit were noted. Decompensation during follow-up was associated with baseline global HIDA <2.915%/min/m2, FRC15HIDA <2.11%/min/m2, and MELD ≥11 (P < .05). CONCLUSIONS: FLIGHT with HIDA-based parameters may complement blood chemistry-based assessments of liver function and facilitate individualized, adaptive liver SBRT planning.


Assuntos
Sistema Biliar/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Iminoácidos/química , Neoplasias Hepáticas/cirurgia , Radiocirurgia , Planejamento da Radioterapia Assistida por Computador/métodos , Cirurgia Assistida por Computador/métodos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Prognóstico , Curva ROC , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos
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