Tangential Volumetric Modulated Arc Therapy for Locally Advanced Breast Cancer.

Cardiovascular toxicity from breast radiation therapy (RT) is a concern to patients and providers. Herein, we present a cardiac-sparing strategy using tangential volumetric modulated arc therapy (tVMAT) in comparison with standard 3-dimensional conformal RT. Ten patients with left-sided breast cancer previously treated with adjuvant RT covering the breast, as well as the axillary and supraclavicular nodal regions, were selected for the study. For each patient, 2 plans were created: a dual-isocenter 3-field 3-dimensional conformal RT plan and a monoisocentric tVMAT plan. The prescription for both techniques was 50 Gy in 25 fractions to the breast and nodal target volumes. Compared with 3-dimensional conformal RT, tVMAT provided more uniform coverage to the breast and regional lymph nodes (mean conformity index: 1.42 for tVMAT vs 2.42 for 3-dimensional conformal RT; P < .01), and the maximum point dose for tVMAT was lower on average (112.8% for tVMAT vs 121.5% for 3-dimensional conformal RT; P < .001). Coverage to the lymph nodes was superior for tVMAT (average minimum coverage to 95% of entire nodal target volumes: 99.5% of prescribed dose for tVMAT vs 94.9% for 3-dimensional conformal RT; P < .001). Organ-at-risk sparing was improved with tVMAT, with a lower average V20Gy for the left lung (15.0% for tVMAT vs 24.6% for 3-dimensional conformal RT; P < .01) and lower mean heart dose (156 cGy for tVMAT vs 200 cGy for 3-dimensional conformal RT; P < .01). Tangential volumetric modulated arc therapy is a promising technique for the treatment of intact breast and regional lymphatics, and it may improve target coverage and organ-at-risk avoidance compared with 3-dimensional conformal techniques.

Single institution experience in re-irradiation of biopsy-proven diffuse intrinsic pontine gliomas.

OBJECTIVES: Diffuse intrinsic pontine glioma (DIPG) is the leading cause of death from CNS tumors in children. Multiple clinical trials have failed to show any benefit from systemic therapy in DIPG, and radiation therapy (RT) alone remains the standard of care. Re-irradiation (rRT) for symptomatic relief is an option at disease progression. However, published data on treatment details and outcomes are limited. The objective of this study was to review and report our institutional experience with re-irradiation of patients with biopsy-proven DIPG. METHODS: We identified a cohort of pediatric patients with biopsy-proven DIPG with clinical disease progression after initial radiotherapy who received a second course of radiotherapy at our institution. We reviewed patient and treatment characteristics and outcomes. RESULTS: Between January 2014 and July 2018, we identified five patients with progressive DIPG who received re-irradiation. Re-irradiation was well tolerated with no serious adverse events reported and all patients experiencing stable to improved neurologic function during treatment. Median survival from completion of re-irradiation was 116 days (range 62 to 159 days). Median overall survival from time of diagnosis was 16.3 months (range 13.0 to 18.0 months), which is longer than the historical average of less than 12 months. In patients with available postmortem neuropathology, common findings were Wallerian degeneration and necrosis. CONCLUSIONS: In our experience, re-irradiation is safe and feasible for patients with DIPG with symptomatic disease progression following initial radiotherapy treatment.

Lipoma gástrico gigante en paciente adulta mayor con síntomas de obstrucción digestiva: Primer reporte de caso en el Perú / Giant gastric lipoma in an elderly patient with digestive obstruction symptoms: First case report in Peru

Los lipomas gástricos son una patología muy rara que representan el 5% de los lipomas gastrointestinales y menos del 1% de los tumores benignos del estómago. Los lipomas gástricos gigantes (≥ 4 cm) son extremadamente raros, habiéndose encontrado solo 32 casos reportados en la bibliografía. Reportamos el primer caso de un lipoma gástrico gigante en el Perú, operado por gastrectomía corporal por laparotomía en una paciente mujer de 79 años que acudió con un cuadro clínico de dos meses de evolución caracterizado por dolor abdominal en epigastrio más sensación de llenura precoz, deposiciones oscuras y pérdida de peso. Al examen físico se halló una masa palpable de aproximadamente 8 cm en hipocondrio izquierdo. La endoscopía digestiva alta reveló una lesión elevada en el tercio proximal del cuerpo gástrico de aproximadamente 30 mm. Se realizó un estudio tomográfico que evidenció una masa sospechosa de lipoma gástrico por lo que se procedió a realizar una gastrectomía corporal por laparotomía. El informe anatomopatológico confirmó el diagnóstico de lipoma gástrico gigante. En el posoperatorio no hubo complicaciones y fue dada de alta al séptimo día.

Gastric lipoma is a very rare condition, which accounts for 5% of gastrointestinal lipomas and for less than 1% of benign tumors of the stomach. Giant gastric lipomas (≥ 4 cm) are extremely rare, and we found only 32 cases reported in the literature. We report the first case of a giant gastric lipoma in Peru, which led to a corporal gastrectomy using a laparotomy approach in a 79-year old woman, who presented with a 2-month history with abdominal and epigastric pain, early fullness, dark stools, and weight loss. Physical examination revealed a 7- to 8-cm palpable mass in the left upper quadrant. Upper gastrointestinal endoscopy revealed an elevated lesion in the proximal third of the gastric body, measuring approximately 30-mm. A CT scan revealed a mass compatible with a gastric lipoma, so a corporal gastrectomy with a laparotomy approach was performed. The anatomopathological report confirmed the diagnosis of a giant gastric lipoma. There were no complications during the postoperative period, and the patient was discharged on the seventh post-op day.

Clinical outcomes and prognostic factors in cisplatin versus cetuximab chemoradiation for locally advanced p16 positive oropharyngeal carcinoma.

OBJECTIVES: Randomized trials evaluating cisplatin versus cetuximab chemoradiation (CRT) for p16+ oropharyngeal cancer (OPC) have yet to report preliminary data. Meanwhile, as a preemptive step toward morbidity reduction, the off-trial use of cetuximab in p16+ patients is increasing, even in those who could potentially tolerate cisplatin. The purpose of this study was to compare the efficacy of cisplatin versus cetuximab CRT in the treatment of p16+ OPC and to identify prognostic factors and predictors of tumor response. MATERIALS AND METHODS: Cases of p16+ OPC treated with cisplatin or cetuximab CRT at our institution from 2010 to 2014 were identified. Recursive partitioning analysis (RPA) classification was used to determine low-risk (LR-RPA) and intermediate-risk (IR-RPA) groups. Log-rank/Kaplan-Meier and Cox Regression methods were used to compare groups. RESULTS: We identified 205 patients who received cisplatin (n = 137) or cetuximab (n = 68) CRT in the definitive (n = 178) or postoperative (n = 27) setting. Median follow-up was 3 years. Cisplatin improved 3-year locoregional control (LRC) [92.7 vs 65.4%], distant metastasis-free survival (DMFS) [88.3 vs 71.2%], recurrence-free survival (RFS) [86.6 vs 50.6%], and overall survival (OS) [92.6 vs 72.2%] compared to cetuximab [all p < .001]. Concurrent cisplatin improved 3-year OS for LR-RPA (97.1 vs 80.3%, p < .001) and IR-RPA (97.1 vs 80.3%, p < .001) groupings. CONCLUSION: When treating p16+ OPC with CRT, the threshold for substitution of cisplatin with cetuximab should be maintained appropriately high in order to prolong survival times and optimize locoregional and distant tumor control. When cetuximab is used in cisplatin-ineligible patients, altered fractionation RT should be considered in an effort to improve LRC.

Synchronous Supraglottic and Esophageal Squamous Cell Carcinomas Treated with a Monoisocentric Hybrid Intensity-Modulated Radiation Technique.

Risk factors for squamous cell carcinomas (SCCs) of the head and neck (HN) and esophagus are similar. As such, synchronous primary tumors in these areas are not entirely uncommon. Definitive chemoradiation (CRT) is standard care for locally advanced HNSCC and is a preferred option for inoperable esophageal SCC. Simultaneous treatment of both primaries with CRT can present technical challenges. We report a case of synchronous supraglottic and esophageal SCC primary tumors, highlighting treatment with a monoisocentric hybrid radiation technique and normal tissue toxicity considerations.

Radical model of arsenic(III) toxicity: theoretical and EPR spin trapping studies.

Arsenic is one of the most environmentally significant pollutants and a great global health concern. Although a growing body of evidence suggests that reactive oxygen species (ROS) mediate the mechanism of arsenic toxicity, the exact mechanism remains elusive. In this study, we examine the capacity of trivalent arsenic species arsenous acid (iAs(III)), monomethylarsonous acid (MMA(III)), and dimethylarsinous acid (DMA(III)) to generate ROS through a theoretical analysis of their structures, redox properties, and their reactivities to various ROS using a density functional theory (DFT) approach at the B3LYP/6-31+G**//B3LYP/6-31G* level of theory and by employing electron paramagnetic resonance (EPR) spin trapping studies using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trap. Results show that the oxidized forms (As(IV)) are structurally more stable compared to the reduced forms (As(II)) that impart elongated As-O bonds leading to the formation of As(III) and hydroxide anion. Enthalpies of one-electron reduction and oxidation indicate that increasing the degree of methylation makes it harder for As(III) to be reduced but easier to be oxidized. The order of increasing favorability for arsenical activation by ROS is O2 < O2(•-) < HO(•), and the oxidation of DMA(III) to DMA(V) is highly exoergic in multiple redox pathways with concomitant generation of radicals. This is followed by MMA(III) and by iAs(III) being the least favorable. Spin trapping studies showed a higher propensity for methylated arsenicals to generate radicals than iAs(III) upon treatment with H2O2. However, in the presence of Fe(II,III), all showed radical generation where MMA(III) gave predominantly C-centered adducts, while acidified iAs (III) and DMA(III) gave primarily HO-adducts, and their formation was affected in the presence of SOD suggesting a As(III)-OO/OOH radical intermediate. Therefore, our results suggest a basis for the increased redox activity of methylated arsenicals that can be applied to the observed trends in arsenic methylation and toxicity in biological systems.

Pharmacological approaches to the treatment of oxidative stress-induced cardiovascular dysfunctions.

Cardiovascular diseases are a growing major global health problem. Our understanding of the mechanisms of pathophysiology of cardiovascular diseases has been gaining significant advances and a wealth of knowledge implicates oxidative stress as a key causative agent. However, to date, most efforts to treat heart failure using conventional antioxidant therapies have been less than encouraging. With increasing incidences of cardiovascular disease in young as well as in aging populations, and the problem of long-term diminishing efficacy of conventional therapeutics, the need for new treatments has never been greater. In this review, [corrected] a variety of therapeutic targets and compounds applied to treat cardiovascular diseases via inhibition of oxidative stress are presented.

Theoretical and experimental studies of the spin trapping of inorganic radicals by 5,5-dimethyl-1-pyrroline N-oxide (DMPO). 3. Sulfur dioxide, sulfite, and sulfate radical anions.

Radical forms of sulfur dioxide (SO(2)), sulfite (SO(3)(2-)), sulfate (SO(4)(2-)), and their conjugate acids are known to be generated in vivo through various chemical and biochemical pathways. Oxides of sulfur are environmentally pervasive compounds and are associated with a number of health problems. There is growing evidence that their toxicity may be mediated by their radical forms. Electron paramagnetic resonance (EPR) spin trapping using the commonly used spin trap, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), has been employed in the detection of SO(3)(•-) and SO(4)(•-). The thermochemistries of SO(2)(•-), SO(3)(•-), SO(4)(•-), and their respective conjugate acids addition to DMPO were predicted using density functional theory (DFT) at the PCM/B3LYP/6-31+G**//B3LYP/6-31G* level. No spin adduct was observed for SO(2)(•-) by EPR, but an S-centered adduct was observed for SO(3)(•-)and an O-centered adduct for SO(4)(•-). Determination of adducts as S- or O-centered was made via comparison based on qualitative trends of experimental hfcc's with theoretical values. The thermodynamics of the nonradical addition of SO(3)(2-) and HSO(3)(-) to DMPO followed by conversion to the corresponding radical adduct via the Forrester-Hepburn mechanism was also calculated. Adduct acidities and decomposition pathways were investigated as well, including an EPR experiment using H(2)(17)O to determine the site of hydrolysis of O-centered adducts. The mode of radical addition to DMPO is predicted to be governed by several factors, including spin population density, and geometries stabilized by hydrogen bonds. The thermodynamic data supports evidence for the radical addition pathway over the nucleophilic addition mechanism.