An Optimized Method for Evaluating the Potential Gd-Nanoparticle Dose Enhancement Produced by Electronic Brachytherapy.

This work reports an optimized method to experimentally quantify the Gd-nanoparticle dose enhancement generated by electronic brachytherapy. The dose enhancement was evaluated considering energy beams of 50 kVp and 70 kVp, determining the Gd-nanoparticle concentration ranges that would optimize the process for each energy. The evaluation was performed using delaminated radiochromic films and a Poly(methyl methacrylate) (PMMA) phantom covered on one side by a thin 2.5 µm Mylar filter acting as an interface between the region with Gd suspension and the radiosensitive film substrate. The results for the 70 kVp beam quality showed dose increments of 6±6%, 22±7%, and 9±7% at different concentrations of 10, 20, and 30 mg/mL, respectively, verifying the competitive mechanisms of enhancement and attenuation. For the 50 kVp beam quality, no increase in dose was recorded for the concentrations studied, indicating that the major contribution to enhancement is from the K-edge interaction. In order to separate the contributions of attenuation and enhancement to the total dose, measurements were replicated with a 12 µm Mylar filter, obtaining a dose enhancement attributable to the K-edge of 29±7% and 34±7% at 20 and 30 mg/mL, respectively, evidencing a significant additional dose proportional to the Gd concentration.

Leveling Up the Access to Radiation Therapy in Latin America: Economic Analysis of Investment, Equity, and Inclusion Opportunities Up to 2030.

PURPOSE: Latin America faces a shortage in radiation therapy (RT) units and qualified personnel for timely and high-quality treatment of patients with cancer. Investing in equitable and inclusive access to RT over the next decade would prevent thousands of deaths. Measuring the investment gap and payoff is necessary for stakeholder discussions and capacity planning efforts. METHODS AND MATERIALS: Data were collected from the International Atomic Energy Agency's Directory of Radiotherapy Centers, industry stakeholders, and individual surveys sent to national scientific societies. Nationwide data on available devices and personnel were compiled. The 10 most common cancers in 2020 with RT indication and their respective incidence rates were considered for gap calculations. The gross 2-year financial return on investment was calculated based on an average monthly salary across Latin America. A 10-year cost projection was calculated according to the estimated population dynamics for the period until 2030. RESULTS: Eleven countries were included in the study, accounting for 557,213,447 people in 2020 and 561 RT facilities. Approximately 1,065,684 new cancer cases were diagnosed, and a mean density of 768,469 (standard deviation ±392,778) people per available unit was found. By projecting the currently available treatment fractions to determine those required in 2030, it was found that 62.3% and 130.8% increases in external beam RT and brachytherapy units are needed from the baseline, respectively. An overall regional investment of approximately United States (US) $349,650,480 in 2020 would have covered the existing demand. An investment of US $872,889,949 will be necessary by 2030, with the expectation of a 2-year posttreatment gross return on investment of more than US $2.1 billion from patients treated in 2030 only. CONCLUSIONS: Investment in RT services is lagging in Latin America in terms of the population's needs. An accelerated outlay could save additional lives during the next decade, create a self-sustaining system, and reduce region-wide inequities in cancer care access. Cash flow analyses are warranted to tailor precise national-level intervention strategies.

Membrane translocation and activation of GnRH receptor sensitize prostate cancer cells to radiation.

BACKGROUND: GnRH analogs are widely used as neoadjuvant agents for radiotherapy in prostate cancer (PCa) patients, with well-documented effects in reducing tumor bulk and increasing progression-free survival. GnRH analogs act locally in the prostate by triggering apoptosis of PCa cells via activation of the GnRH receptor (GnRHR). During PCa progression, the distribution of GnRHR within the cell is altered, with reduced expression in the cell membrane and remaining sequestered in the endoplasmic reticulum. Pharmacoperone IN3 is able to relocalize GnRHR to the cell membrane. The aim of this study was to evaluate the effect of radiation on PCa cells pretreated with leuprolide, alone or in combination with IN3, as radiosensitizers. MATERIAL AND METHODS: PC3 and human PCa primary cell cultures were treated with IN3 for 24 h, followed by different doses of leuprolide for 48 h and, finally, single doses of radiation (3, 6, and 9 Gy). After radiation, cell survival, apoptosis, cell cycle distribution, and colony growth were evaluated. RESULTS: Radiation reduced cell survival and increased apoptosis in a dose-dependent manner. This effect was also directly related to leuprolide concentration. Pretreatment with IN3 enhanced apoptosis and decreased cell survival, also observing a higher proportion of cells arrested in G2. CONCLUSION: Neoadjuvant leuprolide increases radiation-mediated apoptosis of PCa cells. This effect was enhanced by pretreatment with pharmacoperone IN3. Clinical use of IN3 as a radiosensitizer combined with androgen deprivation therapy to improve survival of patients with PCa remains to be evaluated.

[Quality of life in patients with prostate cancer: validation of an instrument for clinical practice]. / Calidad de vida en pacientes con cáncer de próstata: la validación de un instrumento para la práctica clínica.

OBJECTIVES: Currently there are instruments to evaluate the different features of the impact on quality of life in those patients with prostate cancer undergoing any type of treatment, but most of them have 50 or more questions and they are difficult to apply in clinical practice. An English validation of a shortened version of the EPIC (Expanded Prostate Cancer Composite), the most used instrument to measure the quality of life in patients with prostate cancer, has been published recently. This version called EPIC-CP (Expanded Prostate Cancer Composite-Clinical Practice) consists of 16 questions arranged in a page, for easy and rapid clinical application. The objective of this work is to validate a Spanish version of the EPIC-CP. METHOD: An inversa-directa Spanish translation of the original version was performed. The EPIC-CP and EQ5D questionnaires were applied to 46 patients eligible to be subjected to different treatments - open prostatectomy (OP), Robotic Prostatectomy (RP), brachytherapy (Br) or conformational radiotherapy (CR) - and 82 patients already treated (9 OP, 13 RP, 7 Br, 4 CR). For reliability evaluation, the Cronbach's alpha was used to test the internal consistency for each domain of the EPIC-CP. Treated and untreated patients' scores were compared with the Wilcoxon range sum test to assess the sensitivity to change. RESULTS: Cronbach's alpha was elevated in all the EPIC-CP domains (near or greater than 0.7), indicating a high internal consistency. There was no significant difference in age and educational level between treated and untreated patients. We found significant differences between treated and untreated patients in the total EPIC CP score, in the domains of urinary incontinence, bowel function, sexual function and hormonal function. CONCLUSION: The Spanish version of the EPIC-CP is reliable and valid, so it is a useful tool to measure the quality of life in patients with prostate cancer, as well as the impact of different treatments.