Willingness to pay for high-quality remote radiation oncology training in Latin America.

Access to high-quality continuing medical education, particularly in Radiation Oncology, can be challenging in some developing countries due to economic barriers. Despite the current offer of free-access self-educational material, end user training faces a backlog still difficult to overcome. The purpose of this investigation is to report the willingness-to-pay profile of practitioners in Latin America, as a surrogate of quality perception of remote educational resources. Related factors include professional experience and baseline practice confidence levels. Most of practitioners would cover their own expenses, while an increased tendency in less-experienced professionals was observed. However, baseline knowledge confidence levels were not influential in decision making. This report contributes to better know the profile of Latin American professionals, in order to design future educational interventions in the region and bridging the current accessibility gap.

Updates in the Treatment of Breast Cancer with Radiotherapy.

Breast-conserving therapy is one of the most remarkable achievements of modern cancer care. The authors review the evidence supporting the role of adjuvant radiotherapy as the standard of care for breast cancer after breast-conserving surgery, consensus guidelines for margins in invasive cancer disease and ductal carcinoma in situ, the role of partial-breast irradiation and hypofractionated whole-breast irradiation, and the evolving indications for postmastectomy radiation therapy and extent of nodal coverage. Areas of research include specific methods of partial-breast irradiation, interactions between neoadjuvant chemotherapy and radiotherapy, and integration of molecular profiles with the selection of the best treatment modality and timing.

Radiotherapy for Anal Cancer: Intensity-Modulated Radiotherapy and Future Directions.

The treatment of anal cancer has evolved remarkably in the past 30 years. Definitive chemoradiotherapy is the standard of care, allowing organ preservation and maintenance of continence for most patients. This article reviews recent advances in radiotherapy planning and delivery that have resulted in improvements in treatment-related toxicity. Most notably, the advent and wide adoption of intensity-modulated radiotherapy provides a superior toxicity profile compared with older techniques, while maintaining similar oncologic outcomes. Current areas of active research include optimizing and individualizing treatment intensity and possible integration of biologic agents and immunotherapies in the treatment of anal cancer.

An oral HemokineTM, α-methylhydrocinnamate, enhances myeloid and neutrophil recovery following irradiation in vivo.

An oral therapeutic which reduces duration of cytopenias and is active following accidental radiation exposures is an unmet need in radiation countermeasures. Alpha methylhydrocinnamate (ST7) prolongs STAT-5 phosphorylation, reduces growth-factor dependency of multi-lineage cell lines, and stimulates erythropoiesis. Here, ST7 and its isomers were studied for their effects on myeloid progenitors and hematopoietic stem cells (HSCs) following radiation, in nonhuman primates, and murine irradiation models. Addition of ST7 or ST7-S increased CFU-GM production by 1.7-fold (p<0.001), reduced neutrophil apoptosis comparable to G-CSF, and enhanced HSC survival post-radiation by 2-fold, (p=0.028). ST7 and ST7-S administered in normal baboons increased ANC and platelet counts by 50-400%. In sub-lethally-irradiated mice, ANC nadir remained >200/mm3 and neutropenia recovered in 6days with ST7 treatment and 18days in controls (p<0.05). In lethally-irradiated mice, marrow pathology at 15days was hypocellular (10% cellularity) in controls, but normal (55-75% cellularity) with complete neutrophil maturation with ST7-S treatment. Following lethal irradiation, ST7, given orally for 4days, reduced mortality, with 30% survival in ST7-animals vs 8% in controls, (p<0.05). Collectively, the studies indicate that ST7 and ST7-S enhance myeloid recovery post-radiation and merit further evaluation to accelerate hematologic recovery in conditions of radiation-related and other marrow hypoplasias.

Fetal globin gene inducers: novel agents and new potential.

Inducing expression of endogenous fetal globin (gamma-globin) gene expression to 60-70% of alpha globin synthesis produces beta-thalassemia trait globin synthetic ratios and can reduce anemia to a mild level. Several classes of therapeutics have induced gamma-globin expression in beta-thalassemia patients and subsequently raised total hemoglobin levels, demonstrating proof-of-concept of the approach. Butyrate treatment eliminated transfusion requirements in formerly transfusion-dependent patients with treatment for as long as seven years. However, prior generation inducers were not readily applicable for widespread use. Currently, a novel oral dual-action therapeutic, sodium 2,2-dimethylbutyrate, is in clinical trials, an oral decitabine formulation is under development, and agents with complementary mechanisms of action can be applied in combined regimens. Identification of three major genetic trait loci which modulate clinical severity provides avenues for developing tailored regimens. These refinements offer renewed potential to apply fetal globin induction as a treatment approach in patient-friendly regimens that can be used worldwide.

Induction of fetal globin in beta-thalassemia: Cellular obstacles and molecular progress.

Accelerated apoptosis of erythroid progenitors in beta-thalassemia is a significant barrier to definitive therapy because the beneficial effects of fetal globin-inducing agents on globin chain balance may not be inducible in cells in which programmed cell death is established early. Accordingly, our objectives have been to identify methods to decrease cellular apoptosis and to identify orally tolerable fetal globin gene inducers. A pilot clinical trial was conducted to determine whether combined use of a fetal globin gene inducer (butyrate) and rhu-erythropoietin (EPO), the hematopoietic growth factor that prolongs erythroid cell survival and stimulates erythroid proliferation, would produce additive hematologic responses in any thalassemia subjects. Butyrate and EPO were administered in 10 patients. Novel fetal globin gene inducers that also stimulate erythroid proliferation were evaluated for pharmacokinetic profiles. Patients with beta+-thalassemia had relatively low levels of endogenous EPO (<145 mU/mL) and had additive responses to administered EPO and butyrate. Patients with at least one beta 0-globin mutation had higher baseline HbF levels (>60%) and EPO levels (>160 mU/mL), and three-fourths of these subjects responded to the fetal globin gene inducer alone. A few select fetal globin-inducing short-chain fatty acid derivatives that stimulated cell proliferation also had favorable pharmacokinetics. These studies identify a significant subset of thalassemia patients who appear to require exogenous EPO to respond optimally to any HbF inducer, as well as new therapeutic candidates that act on both cellular and molecular pathologies of beta-thalassemia. Both approaches now offer excellent potential for tolerable, definitive treatment of beta-thalassemia.