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PURPOSE: A single treatment planning system (TPS) model for matched linacs provides flexible clinical workflows from patient treatment to intensity-modulated radiation therapy (IMRT) quality assurance (QA) measurement. Since general guidelines for building a single TPS model and its validation for matched linacs are not well established, we present our RayStation photon TPS modeling strategy for matched Elekta VersaHD linacs. METHOD: The four linacs installed from 2013 to 2020 were matched in terms of Percent Depth Dose (PDD), profile, output factor and wedge factors for 6-MV, 10-MV, 15-MV, and 6-MV-FFF, and maintained following TG-142 recommendations until RayStation commissioning. The RayStation single model was built to represent all four linacs within the tolerance limits recommended by MPPG-5.a. The comprehensive validation tests were performed for one linac following MPPG-5.a and TG-119 guidelines, and spot checks for the other three. Our TPS modeling/validation method was evaluated by re-analyzing the previous 103 patient-specific IMRT/volumetric modulated arc therapy (VMAT) QA measurements with the calculated planar doses by the single model in comparison with the analysis results using four individual Pinnacle TPS models. RESULTS: For all energies, our single model PDDs were within 1% agreement of the four-linac commissioning measurements. The MPPG-5.a validation tests from 5.1 through 7.5 and all TG-119 measurements passed within the recommended tolerance limits. The IMRT QA results (mean ± standard deviation) for RayStation single model versus Pinnacle individual models were 98.9% ± 1.3% and 98.0% ± 1.4% for 6-MV, 99.9% ± 0.1% and 99.1% ± 1.9% for 10-MV, and 98.2% ± 1.3% and 97.9% ± 1.8% for 6-MV-FFF, respectively. CONCLUSION: We successfully built and validated a single photon beam model in RayStation for four Elekta Linacs. The proposed new validation methods were proven to be both efficient and effective.
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Statins have historically been underutilized in patients with chronic liver disease (CLD). We sought to investigate the association between CLD and statin prescription in a primary care setting. Our retrospective cohort study identified primary care patients with a low-density lipoprotein value and more than one office visit from 2012 through 2018. Indication for statin therapy was determined using the Third Adult Treatment Panel criteria prior to November 2016 and the American College of Cardiology and American Heart Association guidelines thereafter. Indication for statin prescription and statin therapy by year was determined. Patients with CLD were identified using ICD-9/10 diagnosis codes. In total, 2119 individuals with an indication for statin therapy were identified. Of these individuals, 354 (16.7%) had CLD. Alcoholic and nonalcoholic fatty liver disease comprised 44.9% and 28.5% of the CLD population, respectively; 27.7% had cirrhosis. There was no difference in the prevalence of statin prescriptions when comparing patients with a CLD diagnosis to those without one (57.9 vs 59.9%, p = 0.48). A diagnosis of CLD was also not significantly associated with statin prescription when adjusting for other covariates (odds ratio (OR) 1.02; 95% confidence interval (CI) 0.78-1.33). An alanine aminotransferase level greater than 45 U/L significantly reduced the odds of a statin prescription (OR 0.62; 95% CI 0.44-0.87). Overall, the presence of a CLD diagnosis was not associated with attenuated statin utilization compared to those without a CLD diagnosis. Nevertheless, adherence to guideline indicated statin therapy remains suboptimal and efforts to increase statin utilization in this high-risk population remain prudent.
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Enfermedades Cardiovasculares , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Enfermedad del Hígado Graso no Alcohólico , Adulto , Humanos , Estados Unidos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Estudios Retrospectivos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Prescripciones de Medicamentos , Atención Primaria de Salud , Enfermedades Cardiovasculares/diagnósticoRESUMEN
BACKGROUND: As recommendations for non-invasive fibrosis risk assessment in nonalcoholic fatty liver disease (NAFLD) emerge, it is not known how often they are performed in primary care. AIMS: We investigated the completion of confirmatory fibrosis risk assessment in primary care patients with NAFLD and indeterminate-risk or greater Fibrosis-4 Index (FIB-4) and NAFLD Fibrosis Scores (NFS). METHODS: This retrospective cohort study of electronic health record data from a primary care clinic identified patients with diagnoses of NAFLD from 2012 through 2021. Patients with a diagnosis of a severe liver disease outcome during the study period were excluded. The most recent FIB-4 and NFS scores were calculated and categorized by advanced fibrosis risk. Charts were reviewed to identify the outcome of a confirmatory fibrosis risk assessment by liver elastography or liver biopsy for all patients with indeterminate-risk or higher FIB-4 (≥ 1.3) and NFS (≥ - 1.455) scores. RESULTS: The cohort included 604 patients diagnosed with NAFLD. Two-thirds of included patients (399) had a FIB-4 or NFS score greater than low-risk, 19% (113) had a high-risk FIB-4 (≥ 2.67) or NFS (≥ 0.676) score, and 7% (44) had high-risk FIB-4 and NFS values. Of these 399 patients with an indication for a confirmatory fibrosis test, 10% (41) underwent liver elastography (24) or liver biopsy (18) or both (1). CONCLUSIONS: Advanced fibrosis is a key indicator of future poor health outcomes in patients with NAFLD and a critical signal for referral to hepatology. Significant opportunities exist to improve confirmatory fibrosis risk assessment in patients with NAFLD.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/patología , Estudios Retrospectivos , Hígado/diagnóstico por imagen , Hígado/patología , Medición de Riesgo , Atención Primaria de Salud , Biopsia , Índice de Severidad de la EnfermedadRESUMEN
Objectives: To investigate the utility of a novel serum miRNA biomarker panel to distinguish teratoma from nonmalignant necrotic/fibrotic tissues or nonviable tumours in patients with NSGCT undergoing post-chemotherapy consolidation surgery. Patients and methods: We prospectively collected pre-surgical serum samples from 22 consecutive testicular NSGCT patients with residual NSGCT after chemotherapy undergoing post-chemotherapy consolidation surgery. We measured serum miRNA expression of four microRNAs (miRNA-375, miRNA-200a-3p, miRNA-200a-5p and miRNA-200b-3p) and compared with pathologic findings at time of surgery. Receiver operating characteristic (ROC) curves were performed to assess the ability of these miRNA to differentiate between teratoma and necrosis or viable malignancy. Results: Twenty-two patients with NSGCT were split into two groups based on pathology at time of post-chemotherapy consolidation surgery (teratoma group vs. necrosis/fibrosis/viable tumour group, i.e., NFVT). Patients with teratoma were older at diagnosis compared with those patients with NFVT (median age 28.7 vs. 23.9). Patients with NFVT were more likely to have embryonal carcinoma in their primary tumour (81.8% vs. 27.3%; p = 0.01). The majority of patients in both groups were stage III (63.6% vs. 72.7%). In this analysis, none of the miRNAs had good sensitivity or specificity to predict teratoma. There was no significant association between the expression levels of the miRNAs and the presence of teratoma. There was no statistically significant correlation between any of the miRNAs and teratoma size. Conclusion: This novel miRNA panel (miRNA-375, miRNA-200a-3p, miRNA-200a-5p and miRNA-200b-3p) did not distinguish teratoma from nonmalignant necrotic/fibrotic tissues or nonviable tumours in patients with NSGCT undergoing post-chemotherapy consolidation surgery.
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BACKGROUND: RNA-based genomic risk assessment estimates chemotherapy benefit in patients with hormone-receptor positive (HR+)/Human Epidermal Growth Factor 2-negative (ERBB2-) breast cancer (BC). It is virtually used in all patients with early HR+/ERBB2- BC regardless of clinical recurrence risk. PATIENTS AND METHODS: We conducted a retrospective chart review of adult patients with early-stage (T1-3; N0; M0) HR+/ERBB2- BC who underwent genomic testing using the Oncotype DX (Exact Sciences) 21-genes assay. Clinicopathologic features were collected to assess the clinical recurrence risk, in terms of clinical risk score (CRS) and using a composite risk score of distant recurrence Regan Risk Score (RRS). CRS and RRS were compared to the genomic risk of recurrence (GRS). RESULTS: Between January 2015 and December 2020, 517 patients with early-stage disease underwent genomic testing, and clinical data was available for 501 of them. There was statistically significant concordance between the 3 prognostication methods (P < 0.01). Within patients with low CRS (n = 349), 9.17% had a high GRS, compared to 8.93% in patients with low RRS (n = 280). In patients with grade 1 histology (n = 130), 3.85% had a high GRS and 68.46% had tumors > 1 cm, of whom only 4.49% had a high GRS. Tumor size > 1cm did not associate with a high GRS. CONCLUSION: Genomic testing for patients with grade 1 tumors may be safely omitted, irrespective of size. Our finds call for a better understanding of the need for routine genomic testing in patients with low grade/low clinical risk of recurrence.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Adulto , Humanos , Femenino , Neoplasias de la Mama/terapia , Neoplasias de la Mama/tratamiento farmacológico , Estudios Retrospectivos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , Receptor ErbB-2/metabolismo , Genómica , Medición de Riesgo , Quimioterapia Adyuvante , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismoRESUMEN
Background. Very late recurrence (LR), i.e., >5 years after initial presentation, occurs in about 1% of patients with germ cell tumors of the testis (TGCT) and is associated with poor prognosis. Methods. We retrospectively reviewed the records of patients at the M. D. Anderson Cancer Center who developed LR > 5 years after their initial diagnosis of TGCT. Results. We identified 25 patients who developed LR between July 2007 and August 2020. The median age at the time of LR was 46 years (range, 29−61). Pathology of LR: somatic transformation to carcinoma or sarcoma11, nonseminoma with yolk sac tumor or teratoma11, nonseminoma without yolk sac tumor or teratoma2, not available1. With a median follow-up of 3.5 years, 68% of patients are alive 3 years after LR. Patients with prior post-chemotherapy consolidation surgery do not have statistically significant longer survival compared to patients who did not receive post-chemotherapy consolidation surgery, 83.3% vs. 60.8% at 3 years, respectively, p = 0.50. Conclusions. Patients with LR > 5 years tend to harbor nonseminoma (with yolk sac tumor and or teratoma). Among these patients, a majority who did not undergo surgery to remove residual disease after chemotherapy developed somatic transformation and succumbed to their LR.
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Although genetic changes may be pivotal in the origin of cancer, cellular context is paramount. This is particularly relevant in a progenitor germ cell tumor and its differentiated mature teratoma counterpart when it concerns tumor heterogeneity and cancer dormancy in subsequent second malignancies (subsequent malignant neoplasms (SMNs)). From our tumor registry database, we identified 655 testicular germ cell tumor (TGCT) patients who developed SMNs between January 1990 and September 2018. Of the 113 solid organ SMNs, 42 had sufficient tumor tissue available for fluorescence in situ hybridization (FISH) analysis of isochromosome 12p [i(12p)]. We identified seven additional patients for targeted DNA and RNA sequencing of teratomas and adjacent somatic transformation. Finally, we established cell lines from freshly resected post-chemotherapy teratomas and evaluated the cells for stemness expression by flow cytometry and by the formation of teratomas in a xenograft model. In our cohort, SMNs comprising non-germ cell tumors occurred about 18 years after a diagnosis of TGCT. Of the 42 SMNs examined, 5 (12%) contained i(12p) and 16 (38%) had 12p gain. When comparing a teratoma and adjacent somatic transformation, targeted DNA and RNA sequencing demonstrated high concordance. Studies of post-chemotherapy teratoma-derived cell lines revealed cancer-initiating cells expressing multipotency as well as early differentiation markers. For the first time, we demonstrated the prevalence of i(12p) in SMNs and the presence of progenitor cells embedded within mature teratomas after chemotherapy. Our findings suggest a progenitor stem-like cell of origin in SMN and TGCT and highlight the importance of cellular context in this disease.
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Hypoxia-inducible factor-1 (HIF-1) is a key regulator of erythropoiesis. In this article, we report 3 novel mutations, P378S, A385T, and G206C, on the EGLN1 gene encoding the negative HIF-1α regulator prolyl hydroxylase domain-2 (PHD2) in 3 patients with isolated erythrocytosis. These mutations impair PHD2 protein stability and partially reduce PHD2 activity, leading to increased HIF-1α protein levels in cultured cells.
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Prolina Dioxigenasas del Factor Inducible por Hipoxia/genética , Policitemia/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación Missense , Procolágeno-Prolina Dioxigenasa/genéticaRESUMEN
BACKGROUND: The objective of this study was to determine whether standardized treatment of germ cell tumors (GCTs) could overcome sociodemographic factors limiting patient care. METHODS: The records of all patients undergoing primary treatment for GCTs at both a public safety net hospital and an academic tertiary care center in the same metropolitan area were analyzed. Both institutions were managed by the same group of physicians in the context of multidisciplinary cancer care. Patients were grouped by care center; clinicopathologic features and outcomes were analyzed. RESULTS: Between 2006 and 2018, 106 and 95 patients underwent initial treatment for GCTs at the safety net hospital and the tertiary care center, respectively. Safety net patients were younger (29 vs 33 years; P = .005) and were more likely to be Hispanic (79% vs 11%), to be uninsured (80% vs 12%; P < .001), to present via the emergency department (76% vs 8%; P < .001), and to have metastatic (stage II/III) disease (42% vs 26%; P = .025). In a multivariable analysis, an absence of lymphovascular invasion (odds ratio [OR], 0.30; P = .008) and an embryonal carcinoma component (OR, 0.36; P = .02) were associated with decreased use of adjuvant treatment for stage I patients; hospital setting was not (OR, 0.67; P = .55). For patients with stage II/III nonseminomatous GCTs, there was no difference in the performance of postchemotherapy retroperitoneal lymph node dissection between the safety net hospital and the tertiary care center (52% vs 64%; P = .53). No difference in recurrence rates was observed between the cohorts (5% vs 6%; P = .76). CONCLUSIONS: Sociodemographic factors are often associated with adverse clinical outcomes in the treatment of GCTs; they may be overcome with integrated, standardized management of testicular cancer.
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Neoplasias Testiculares/epidemiología , Adulto , Humanos , Masculino , Proveedores de Redes de Seguridad , Factores SocioeconómicosRESUMEN
BACKGROUND: In treating glioblastoma, irradiation of the neural progenitor cell (NPC) niches is controversial. Lower hippocampal doses may limit neurocognitive toxicity, but higher doses to the subventricular zones (SVZ) may improve survival. OBJECTIVE: To prospectively evaluate the impact of limiting radiation dose to the NPC niches on tumor progression, survival, and cognition in patients with glioblastoma. METHODS: Patients with glioblastoma received resection followed by standard chemoradiation. Radiation dose to the NPC niches, including the bilateral hippocampi and SVZ, was minimized without compromising tumor coverage. The primary outcome was tumor progression in the spared NPC niches. Follow-up magnetic resonance imaging was obtained bimonthly. Neurocognitive testing was performed before treatment and at 6- and 12-mo follow-up. Cox regression evaluated predictors of overall and progression-free survival. Linear regression evaluated predictors of neurocognitive decline. RESULTS: A total of 30 patients enrolled prospectively. The median age was 58 yr. Median mean doses to the hippocampi and SVZ were 49.1 and 41.8 gray (Gy) ipsilaterally, and 16.5 and 19.9 Gy contralaterally. Median times to death and tumor progression were 16.0 and 7.6 mo, and were not significantly different compared to a matched historical control. No patients experienced tumor progression in the spared NPC-containing regions. Overall survival was associated with neurocognitive function (P ≤ .03) but not dose to the NPC niches. Higher doses to the hippocampi and SVZ predicted greater decline in verbal memory (P ≤ .01). CONCLUSION: In treating glioblastoma, limiting dose to the NPC niches may reduce cognitive toxicity while maintaining clinical outcomes. Further studies are needed to confirm these results.
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Neoplasias Encefálicas/terapia , Quimioradioterapia/métodos , Irradiación Craneana/métodos , Glioblastoma/terapia , Nicho de Células Madre/efectos de la radiación , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Quimioradioterapia/efectos adversos , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/prevención & control , Estudios de Cohortes , Irradiación Craneana/efectos adversos , Femenino , Glioblastoma/mortalidad , Glioblastoma/patología , Hipocampo/efectos de la radiación , Humanos , Ventrículos Laterales/efectos de la radiación , Masculino , Persona de Mediana Edad , Células-Madre Neurales/efectos de la radiación , Estudios Prospectivos , Temozolomida/uso terapéuticoRESUMEN
INTRODUCTION: The five-year survival rate for patients with glioblastoma (GBM) is low at approximately 4.7%. Radiotherapy plus concomitant and adjuvant temozolomide (TMZ) remains the standard of care. The optimal duration of therapy with TMZ is unknown. This study sought to evaluate the survival benefit of two years of treatment. METHODS: This was a retrospective chart review of all patients diagnosed with GBM and treated with TMZ for up to two years between January 1, 2002 and December 31, 2011. The Kaplan-Meier method with log-rank test was used to estimate the progression-free survival (PFS) and the overall survival (OS). The results were compared to historical controls and data from previous clinical trials of patients treated up to one year. RESULTS: Data from 56 patients with confirmed GBM were evaluated. The OS probability was 54% (SE = 0.068) at one year, 28.3% (SE = 0.064) at two years, 17.8% (SE = 0.059) at three years, and 4% (SE = 0.041) at five years. Seven patients (12.5%) were treated with TMZ for two years. Their median time-to-progression was 28 months (95% CI = 5.0 - 28.0), and they had an increased survival probability at three years compared to other patients (log-rank test χ2 (1, N = 56) = 19.2, p < 0.0001). CONCLUSIONS: There may be an advantage for a longer duration of TMZ therapy among patients with GBM, but the sample size was too small for generalization. A multicenter prospective study is needed to identify optimal duration of TMZ therapy.
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PURPOSE: The purpose of this work was to compare the dosimetry and delivery times of 3D-conformal (3DCRT)-, volumetric modulated arc therapy (VMAT)-, and tomotherapy-based approaches for spatially fractionated radiation therapy for deep tumor targets. METHODS: Two virtual GRID phantoms were created consisting of 7 "target" cylinders (1-cm diameter) aligned longitudinally along the tumor in a honey-comb pattern, mimicking a conventional GRID block, with 2-cm center-to-center spacing (GRID2 cm ) and 3-cm center-to-center spacing (GRID3 cm ), all contained within a larger cylinder (8 and 10 cm in diameter for the GRID2 cm and GRID3 cm , respectively). In a single patient, a GRID3 cm structure was created within the gross tumor volume (GTV). Tomotherapy, VMAT (6 MV + 6 MV-flattening-filter-free) and multi-leaf collimator segment 3DCRT (6 MV) plans were created using commercially available software. Two tomotherapy plans were created with field widths (TOMO2.5 cm ) 2.5 cm and (TOMO5 cm ) 5 cm. Prescriptions for all plans were set to deliver a mean dose of 15 Gy to the GRID targets in one fraction. The mean dose to the GRID target and the heterogeneity of the dose distribution (peak-to-valley and peak-to-edge dose ratios) inside the GRID target were obtained. The volume of normal tissue receiving 7.5 Gy was determined. RESULTS: The peak-to-valley ratios for GRID2 cm /GRID3 cm /Patient were 2.1/2.3/2.8, 1.7/1.5/2.8, 1.7/1.9/2.4, and 1.8/2.0/2.8 for the 3DCRT, VMAT, TOMO5 cm , and TOMO2.5 cm plans, respectively. The peak-to-edge ratios for GRID2 cm /GRID3 cm /Patient were 2.8/3.2/5.4, 2.1/1.8/5.4, 2.0/2.2/3.9, 2.1/2.7/5.2 and for the 3DCRT, VMAT, TOMO5 cm , and TOMO2.5 cm plans, respectively. The volume of normal tissue receiving 7.5 Gy was lowest in the TOMO2.5 cm plan (GRID2 cm /GRID3 cm /Patient = 54 cm3 /19 cm3 /10 cm3 ). The VMAT plans had the lowest delivery times (GRID2 cm /GRID3 cm /Patient = 17 min/8 min/9 min). CONCLUSION: Our results present, for the first time, preliminary evidence comparing IMRT-GRID approaches which result in high-dose "islands" within a target, mimicking what is achieved with a conventional GRID block but without high-dose "tail" regions outside of the target. These approaches differ modestly in their ability to achieve high peak-to-edge ratios and also differ in delivery times.
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Neoplasias/radioterapia , Órganos en Riesgo/efectos de la radiación , Fantasmas de Imagen , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Conformacional/métodos , Radioterapia de Intensidad Modulada/métodos , Programas Informáticos , Humanos , Dosificación RadioterapéuticaRESUMEN
PURPOSE: In radiotherapy, it is necessary to characterize dose over the patient anatomy to target areas and organs at risk. Current tools provide methods to describe dose in terms of percentage of volume and magnitude of dose, but are limited by assumptions of anatomical homogeneity within a region of interest (ROI) and provide a non-spatially aware description of dose. A practice termed radio-morphology is proposed as a method to apply anatomical knowledge to parametrically derive new shapes and substructures from a normalized set of anatomy, ensuring consistently identifiable spatially aware features of the dose across a patient set. METHODS: Radio-morphologic (RM) features are derived from a three-step procedure: anatomy normalization, shape transformation, and dose calculation. Predefined ROI's are mapped to a common anatomy, a series of geometric transformations are applied to create new structures, and dose is overlaid to the new images to extract dosimetric features; this feature computation pipeline characterizes patient treatment with greater anatomic specificity than current methods. RESULTS: Examples of applications of this framework to derive structures include concentric shells based around expansions and contractions of the parotid glands, separation of the esophagus into slices along the z-axis, and creating radial sectors to approximate neurovascular bundles surrounding the prostate. Compared to organ-level dose-volume histograms (DVHs), using derived RM structures permits a greater level of control over the shapes and anatomical regions that are studied and ensures that all new structures are consistently identified. Using machine learning methods, these derived dose features can help uncover dose dependencies of inter- and intra-organ regions. Voxel-based and shape-based analysis of the parotid and submandibular glands identified regions that were predictive of the development of high-grade xerostomia (CTCAE grade 2 or greater) at 3-6 months post treatment. CONCLUSIONS: Radio-morphology is a valuable data mining tool that approaches radiotherapy data in a new way, improving the study of radiotherapy to potentially improve prognostic and predictive accuracy. Further applications of this methodology include the use of parametrically derived sub-volumes to drive radiotherapy treatment planning.
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Radioterapia Guiada por Imagen/métodos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
PURPOSE: For patients with localized pancreatic cancer (PC) with vascular involvement, prediction of resectability is critical to define optimal treatment. However, the current definitions of borderline resectable (BR) and locally advanced (LA) disease leave considerable heterogeneity in outcomes within these classifications. Moreover, factors beyond vascular involvement likely affect the ability to undergo resection. Herein, we share our experience developing a model that incorporates detailed radiologic, patient, and treatment factors to predict surgical resectability in patients with BR and LA PC who undergo stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Patients with BR or LA PC who were treated with SBRT between 2010 and 2016 were included. The primary endpoint was margin negative resection, and predictors included age, sex, race, treatment year, performance status, initial staging, tumor volume and location, baseline and pre-SBRT carbohydrate antigen 19-9 levels, chemotherapy regimen and duration, and radiation dose. In addition, we characterized the relationship between tumors and key arteries (superior mesenteric, celiac, and common hepatic arteries), using overlap volume histograms derived from computed tomography data. A classification and regression tree was built, and leave-one-out cross-validation was performed. Prediction of surgical resection was compared between our model and staging in accordance with the National Comprehensive Care Network guidelines using McNemar's test. RESULTS: A total of 191 patients were identified (128 patients with LA and 63 with BR), of which 87 patients (46%) underwent margin negative resection. The median total dose was 33 Gy. Predictors included the chemotherapy regimen, amount of arterial involvement, and age. Importantly, radiation dose that covers 95% of gross tumor volume (GTV D95), was a key predictor of resectability in certain subpopulations, and the model showed improved accuracy in the prediction of margin negative resection compared with National Comprehensive Care Network guideline staging (75% vs 63%; P < .05). CONCLUSIONS: We demonstrate the ability to improve prediction of surgical resectabiliy beyond the current staging guidelines, which highlights the value of assessing vascular involvement in a continuous manner. In addition, we show an association between radiation dose and resectability, which suggests the potential importance of radiation to allow for resection in certain populations. External data are needed for validation and to increase the robustness of the model.
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OBJECTIVE: We explore whether a knowledge-discovery approach building a Classification and Regression Tree (CART) prediction model for weight loss (WL) in head and neck cancer (HNC) patients treated with radiation therapy (RT) is feasible. METHODS AND MATERIALS: HNC patients from 2007 to 2015 were identified from a prospectively collected database Oncospace. Two prediction models at different time points were developed to predict weight loss ≥5 kg at 3 months post-RT by CART algorithm: (1) during RT planning using patient demographic, delineated dose data, planning target volume-organs at risk shape relationships data and (2) at the end of treatment (EOT) using additional on-treatment toxicities and quality of life data. RESULTS: Among 391 patients identified, WL predictors during RT planning were International Classification of Diseases diagnosis; dose to masticatory and superior constrictor muscles, larynx, and parotid; and age. At EOT, patient-reported oral intake, diagnosis, N stage, nausea, pain, dose to larynx, parotid, and low-dose planning target volume-larynx distance were significant predictive factors. The area under the curve during RT and EOT was 0.773 and 0.821, respectively. CONCLUSIONS: We demonstrate the feasibility and potential value of an informatics infrastructure that has facilitated insight into the prediction of WL using the CART algorithm. The prediction accuracy significantly improved with the inclusion of additional treatment-related data and has the potential to be leveraged as a strategy to develop a learning health system.
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Big clinical data analytics as a primary component of precision medicine is discussed, identifying where these emerging tools fit in the spectrum of genomics and radiomics research. A learning health system (LHS) is conceptualized that uses clinically acquired data with machine learning to advance the initiatives of precision medicine. The LHS is comprehensive and can be used for clinical decision support, discovery, and hypothesis derivation. These developing uses can positively impact the ultimate management and therapeutic course for patients. The conceptual model for each use of clinical data, however, is different, and an overview of the implications is discussed. With advancements in technologies and culture to improve the efficiency, accuracy, and breadth of measurements of the patient condition, the concept of an LHS may be realized in precision radiation therapy.
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Macrodatos , Sistemas de Apoyo a Decisiones Clínicas , Aprendizaje Automático , Medicina de Precisión/métodos , Oncología por Radiación/métodos , Minería de Datos/métodos , Genómica , Humanos , Modelos Estadísticos , Neoplasias/patología , Neoplasias/radioterapia , Radioterapia/efectos adversosAsunto(s)
Linfedema/diagnóstico , Linfedema/terapia , Neoplasias/complicaciones , Humanos , Linfedema/etiología , PronósticoRESUMEN
A substantial barrier to the single- and multi-institutional aggregation of data to supporting clinical trials, practice quality improvement efforts, and development of big data analytics resource systems is the lack of standardized nomenclatures for expressing dosimetric data. To address this issue, the American Association of Physicists in Medicine (AAPM) Task Group 263 was charged with providing nomenclature guidelines and values in radiation oncology for use in clinical trials, data-pooling initiatives, population-based studies, and routine clinical care by standardizing: (1) structure names across image processing and treatment planning system platforms; (2) nomenclature for dosimetric data (eg, dose-volume histogram [DVH]-based metrics); (3) templates for clinical trial groups and users of an initial subset of software platforms to facilitate adoption of the standards; (4) formalism for nomenclature schema, which can accommodate the addition of other structures defined in the future. A multisociety, multidisciplinary, multinational group of 57 members representing stake holders ranging from large academic centers to community clinics and vendors was assembled, including physicists, physicians, dosimetrists, and vendors. The stakeholder groups represented in the membership included the AAPM, American Society for Radiation Oncology (ASTRO), NRG Oncology, European Society for Radiation Oncology (ESTRO), Radiation Therapy Oncology Group (RTOG), Children's Oncology Group (COG), Integrating Healthcare Enterprise in Radiation Oncology (IHE-RO), and Digital Imaging and Communications in Medicine working group (DICOM WG); A nomenclature system for target and organ at risk volumes and DVH nomenclature was developed and piloted to demonstrate viability across a range of clinics and within the framework of clinical trials. The final report was approved by AAPM in October 2017. The approval process included review by 8 AAPM committees, with additional review by ASTRO, European Society for Radiation Oncology (ESTRO), and American Association of Medical Dosimetrists (AAMD). This Executive Summary of the report highlights the key recommendations for clinical practice, research, and trials.