Applications and perspectives of tumor organoids in radiobiology (Review).

Radiotherapy exhibits significant versatility and efficacy in cancer treatment, thereby playing a crucial role in the field of oncology. However, there remains an urgent need for extensive research on various aspects of radiotherapy, including target selection, damage repair and its combination with immunotherapy. Particularly, the development of in vitro models to replicate in vivo tumor lesion responses is vital. The present study provides a thorough review of the establishment and application of tumor organoids in radiotherapy, aiming to explore their potential impact on cancer treatment.

RadPhysBio: A Radiobiological Database for the Prediction of Cell Survival upon Exposure to Ionizing Radiation.

Based on the need for radiobiological databases, in this work, we mined experimental ionizing radiation data of human cells treated with X-rays, γ-rays, carbon ions, protons and α-particles, by manually searching the relevant literature in PubMed from 1980 until 2024. In order to calculate normal and tumor cell survival α and ß coefficients of the linear quadratic (LQ) established model, as well as the initial values of the double-strand breaks (DSBs) in DNA, we used WebPlotDigitizer and Python programming language. We also produced complex DNA damage results through the fast Monte Carlo code MCDS in order to complete any missing data. The calculated α/ß values are in good agreement with those valued reported in the literature, where α shows a relatively good association with linear energy transfer (LET), but not ß. In general, a positive correlation between DSBs and LET was observed as far as the experimental values are concerned. Furthermore, we developed a biophysical prediction model by using machine learning, which showed a good performance for α, while it underscored LET as the most important feature for its prediction. In this study, we designed and developed the novel radiobiological 'RadPhysBio' database for the prediction of irradiated cell survival (α and ß coefficients of the LQ model). The incorporation of machine learning and repair models increases the applicability of our results and the spectrum of potential users.

Evaluation of Cell Cycle-Dependent Migration Activity after X-ray Exposure: A Radiobiological Approach for Optimization of Radiotherapy with Cell Cycle-Targeting Agents.

Radiotherapy with cell cycle-specific anticancer agents has become an important option in the control of both primary tumors and metastases. Here, we used image analysis algorithms that enable quick segmentation and tracking to describe a radiobiological approach for the optimized selection of cell cycle-targeting anticancer drugs for radiotherapy. We confirmed cell cycle-synchronization using human cervical cancer HeLa cells expressing a fluorescent ubiquitination-based cell cycle indicator (FUCCI) as a cell cycle-monitoring probe. Cells synchronized in the G1 and G2 phases were irradiated with X rays at 0.5-2 Gy. Each cell was identified using Cellpose, a deep learning-based algorithm for cellular segmentation, and the velocity and direction of migration were analyzed using the TrackMate plugin in Fiji ImageJ. G1 phase synchronized cells showed a dose-dependent decrease in velocity after irradiation, while G2 cells tended to increase their velocity. The migration pattern of all cells appeared to be a random walk model, regardless of the exposure dose. In addition, we used cisplatin to arrest the cell cycle. HeLa-FUCCI cells arrested at the G2 phase via cisplatin treatment showed enhanced cell migration after X-ray exposure. These results indicated that anticancer agents that arrest the cell cycle of cancer cells in a specific phase may enhance cell migration after radiotherapy. Our approach, using cellular segmentation and tracking algorithms, could enhance the radiobiological assessment of cell cycle-specific migration after irradiation to aid in optimizing radiotherapy using cell cycle-targeting agents.

Intra-fractional dose rate effect in continuous and interrupted irradiation of the MCF-7 cell line: Possible radiobiological implications for breath-hold techniques in breast radiotherapy?

PURPOSE: To investigate the effects of different dose rates (DRs) in continuous and interrupted irradiation on in-vitro survival of the MCF-7 cell line, towards finding possible radiobiological effects of breath-hold techniques in breast radiotherapy (RT), in which intra-fractional beam interruptions and delivery prolongation can occur. MATERIALS AND METHODS: MCF-7 cells were irradiated continuously or with regular interruptions using 6 MV x-rays at different accelerator DRs (50-400 cGy/min) to deliver a 2 Gy dose. The interrupted irradiation was delivered in a 10 s on, 10 s off manner. Then, cell survival and viability were studied using colony and MTT assays, respectively. RESULTS: Survival and viability with continuous and interrupted irradiation were similar ( P > 0.5). A significant increase in survival at 50, 100, and 400 cGy/min compared to 200 and 300 cGy/min was observed, also a significant decreasing and then increasing trend from 50 to 200 cGy/min and 200 to 400 cGy/min, respectively ( P < 0.04). Relative to 200 cGy/min, the survival fractions at 50, 100, 300, and 400 cGy/min were 1.24, 1.23, 1.05, and 1.20 times greater, respectively. Cell viability did not show significant differences between the DRs, despite following the same trend as cell survival. CONCLUSION: Our results suggest that for continuous irradiation of in-vitro MCF-7 cells, with increasing DR within the 50-400 cGy/min range, sensitivity increases and then decreases (inverse effect), also that up to doubling of treatment time in breath-hold techniques does not affect in-vitro radiobiological efficacy with 200-400 cGy/min accelerator DRs. Further confirmatory studies are required.

On the use of radiobiological-based optimization functions in radiotherapy treatment planning for prostate and head and neck cases on Monaco and Eclipse TPS / Sobre el uso de funciones de costo basadas en radiobiología en la planeación de tratamientos de radioterapia para casos de próstata y cabeza y cuello en los TPS Monaco y Eclipse

INTRODUCTION Radiobiological-based optimization functions for radiotherapy treatment planning involve dose-volume effects that could allow greater versatility when shaping dose distributions and DVHs than traditional dose volume (DV) criteria. Two of the most commercially available TPS (Monaco and Eclipse) already offer biological-based optimization functions, but they are not routinely used by most planners in clinical practice. Insight into the benefits of using EUD, TCP/NTCP-based cost functions in Monaco and Eclipse TPS was gained by comparing biological-based optimizations and physical-based optimizations for prostate and head and neck cases. METHODS Three prostate and three H&N cases were retrospectively optimized in Monaco and Eclipse TPS, using radiobiological-based cost functions vs DV-based cost functions. Plan comparison involved ICRU Report 83 parameters D95%, D50%, D2% and TCP for the PTV, and NTCP and RTOG tolerance doses for OARs. RESULTS Although there were differences between Monaco and Eclipse plans due to their dissimilar optimization and dose calculation algorithms as well as optimization functions, both TPS showed that radiobiological-based criteria allow versatile tailoring of the DVH with variation of only one parameter and at most two cost functions, in contrast to the use of three to four DV-based criteria to reach a similar result. CONCLUSION Despite the use of a small sample, optimization of three prostate and three head and neck cases allowed the exploration of optimization possibilities offered by two of the most commercially available TPS on two anatomically dissimilar regions. Radiobiological-based optimization efficiently drives dose distributions and DVH shaping for OARs without sacrifice of PTV coverage. Use of EUD-based cost functions should be encouraged in addition to DV cost functions to obtain the best possible plan in daily clinical practice

INTRODUCCION Las funciones de optimización basadas en radiobiología para la planificación del tratamiento de radioterapia implican efectos dosis volumen que podrían permitir una mayor versatilidad a la hora de dar forma a las distribuciones de dosis y DVH que los tradicionales criterios dosis-volumen (DV). Dos de los TPS más disponibles comercialmente (Mónaco y Eclipse) ya ofrecen productos de funciones de optimización de base biológica, pero la mayoría de los planificadores no las utilizan de forma rutinaria en la práctica clínica. El conocimiento de los beneficios del uso de las funciones de costos basadas en EUD, TCP/NTCP en Mónaco y Eclipse TPS se obtuvo comparando optimizaciones de base biológica y optimizaciones físicas para casos de próstata y cabeza y cuello. MÉTODOS Tres próstatas y tres casos de H&N en Mónaco y Eclipse TPS fueron optimizadas retrospectivamente usando funciones de costos basadas en radiobiología vs funciones de costos basadas en DV. La comparación de planes involucró los parámetros del Informe ICRU 83 D95%, D50%, D2% y TCP para el PTV, y dosis de tolerancia NTCP y RTOG para OAR. Resultados. Aunque hubo diferencias entre los planes Mónaco y Eclipse, debido a sus diferentes algoritmos de optimización y cálculo de dosis, así como funciones de optimización, ambos TPS demostraron que el criterio basado en radiobiología permiten una adaptación versátil del DVH con variación de un solo parámetro y como máximo dos funciones de costos, en contraste con el uso de tres o cuatro criterios basados en DV para alcanzar un resultado similar. CONCLUSIÓN A pesar del uso de una muestra pequeña, la optimización de tres casos de próstata y tres de cabeza y cuello permitió la exploración de las posibilidades de optimización que ofrecen dos de los TPS más disponibles comercialmente en dos regiones anatómicamente diferentes. La optimización basada en radiobiología impulsa de manera eficiente las distribuciones de dosis y la configuración de DVH para OAR sin sacrificar Cobertura de PTV. Se debe fomentar el uso de funciones de costos basadas en EUD además de las funciones de costos DV para obtener el mejor posible plan en la práctica clínica diaria

Fístulas rectovaginales actínicas experiencia en el I.O.L.R / Actnics rectovaginal fistulas: experience in the I.O.L.R

Siendo la morbimortalidad del carcinoma invasor del cérvix uterino tan elevada, tanto por la patología per se como por el tratamiento que requiere para su erradicación, debe insistirse en su prevención. Se reconoce a la Radioterapia, en cualquiera de sus modalidades de administración, como el tratamiento idóneo; sin embargo, no está exenta de graves y penosas complicaciones. Cuando se ha logrado el control de la actividad neoplásica, resulta incongruente que los efectos adversos del tratamiento aplicado, sean más severos que los ocasionados por la enfermedad primaria. Desde 1958, se han registrado un total de 127 casos de pacientes que desarrollaron una Fístula Recto-Vaginal de origen actínico, durante el tratamiento radiante de un carcinoma de cuello uterino, en el Instituto de Oncología "Luis Razetti" de Caracas. A todas estas pacientes se les realizó alguna modalidad de tratamiento quirúrgico con miras a restablecer la continuidad del septum rectovaginal. La finalidad del tratamiento quirúrgico fue sustituir el tejido irradiado, sometido a una isquemia crónica, por un tejido sano. Para ello se consideró previamente, la derivación fecal mediante la realización de una Colostomía. Posteriormente, un procedimiento de reparación local, combinando técnicas de colpoplastia y migración de tejido viable no irradiado (Descenso o Pulthrough y/o Injerto pediculados). El grupo estudiado resultó ser muy heterogéneo, y al carecer de un protocolo reconocido para el manejo de las complicaciones actínicas, fue muy laborioso evaluar la efectividad de los tratamientos realizados. Sin embargo, se pudo apreciar una tendencia mayor a favorecer los tratamientos combinados para alcanzar los objetivos previstos en la reparación del septum rectovaginal irradiado. El éxito se logró sólo en 18 pacientes, no pudiendo demostrar la efectividad de los tratamientos realizados. Sin embargo, se pudo apreciar una tendencia mayor a favorecer los tratamientos combinados para alcanzar los objetivos previstos en la reparación del septum rectovaginal irradiado. El éxito se logró sólo en 18 pacientes, no pudiendo demostrar la efectividad de un único esquema terapéutico. Debemos concluir que la prevención del carcinoma del cuello uterino y de los efectos actínicos severos a consecuencia de su tratamiento, es primordial. El control local de la infección y la sustitución del tejido desvitalizado por el tejido no irradiado, es la maniobra terapéutica a seguir una vez establecida la fístula