Efecto de la hipoxia-reoxigenación y las radiaciones ionizantes en la captación de glucosa en líneas tumorales de seno y colon cocultivadas con células endoteliales.

La captación de glucosa y su conversión en lactato juega un papel fundamental en el metabolismo tumoral, independientemente de la concentración de oxígeno presente en el tejido (efecto Warburg). Sin embrago, dicha captación varía de un tipo tumoral a otro, y dentro del mismo tumor, situación que podría depender de las características microambientales tumorales (fluctuaciones de oxígeno, presencia de otros tipos celulares) y de factores estresores asociados a los tratamientos. Se estudió el efecto de la hipoxia-reoxigenación (HR) y las radiaciones ionizantes (RI) sobre la captación de glucosa, en cultivos de líneas tumorales MCF-7 y HT-29, cultivadas de forma aislada o en cocultivo con la línea celular EAhy296. Se encontró que la captación de glucosa en HR es diferente para lo descrito en condiciones de hipoxia permanente y que es modificada en el cocultivo. Se identificaron poblaciones celulares dentro de la misma línea celular, de alta y baja captación de glucosa, lo que implicaría una simbiosis metabólica de la célula como respuesta adaptativa a las condiciones tumorales. Se evaluó la expresión de NRF2 y la translocación nuclear de NRF2 y HIF1a, como vías de respuesta a estrés celular e hipoxia. La translocación nuclear de las proteínas evaluadas explicaría el comportamiento metabólico de las células tumorales de seno, pero no de colon, por lo cual deben existir otras vías metabólicas implicadas. Las diferencias en el comportamiento de las células tumorales en HR en relación con hipoxia permitirá realizar planeaciones dosimétricas más dinámicas, que reevalúen las condiciones de oxigenación tumoral constantemente.

Avaliação da dose de radiação absorvida em exames radiológicos durante o planejamento radioterápico

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Modelos de tratamento para adenocarcinomas de próstata tratados por radioterapia conformacional 3D

Radiotherapy is a branch of medical physics related to the treatment of malignant neoplasm, being an important instrument in the fight against cancer, when combined with the effort of a multidisciplinary team, composed of, physicians, physicists, nurses and technicians. Every year more than 3.5 million new cases of cancer are recorded in the world, being the prostate cancer responsible for approximately 25% of this amount (INCA and IARC, 2008). In this type of cancer, radiotherapy is a method indicated for treatement. The technological advance in this area over years has allowed a greater accuracy in the tumor location, more conformation of the radiation beam around the tumor, reducing the dose in healthy tissues and a consequent dose increase on treatment (Bedford et al., 1999). A radiotherapy planning, in which the physicist develops an important role, is composed of several steps, including choosing the best configuration of treatment beams. This choice has a close relationship with success of therapy and is critical to achieve the best distribution of dose inside the tumor and expose the least as possible the healthy tissue to radiation. In this work, two options for setting up camps in the first phase in a treatment of prostate cancer were simulated in computer planning: 4 fields orthogonal or “Box” with gantry angles in 00, 1800, 2700 e 90° and 4 fields angled or “X” (1350, 450, 3150 e 2250). The percentage of the rectal volume exposed to 40, 50, 60, 72 and 76 Gy should be limited to 60, 50, 25, 15 and 5% respectively (Greco et al., 2003). The femoral toxicity have limited dose by 70% of the total dose prescribed in a prostate treatment (Bedford et al., 1999). The planning of 27 patients with prostate adenocarcinoma submitted to 3D conformal radiotherapy were accompanied. As a result, it was assessed that the best TCP (tumor control probability)... (Complete abstract click electronic access below)

Análise quantitativa dos parâmetros físicos e radiométricos de procedimetnos radioterapicos em tumores de mama

The paper presents the radiometric parameters determined by the medical physicist during routine radiotherapy planning service in cases of breast cancer . The contours of the breast volume in patients undergoing radiation breast tumors at the Hospital das Clinicas, Faculty of Medicine , UNESP, Botucatu ( HCFMB ) during the year 2012 were analyzed . In order to analyze the influence of physical and radiometric parameters for the determination of the dose distribution of irradiated breast volume , four measurements of isodose curves were prepared in four different heights breast , and compared with the isodose curves plotted computationally . In the routine of planning , the medical physicist must determine the isodose curve that gives the best dose distribution homogeneity in the irradiated volume . The choice of the treatment plan can be done by dedicated computer systems , which require significantly costly investments available services having better financial support . In the Service of Medical Physics , Department of Radiotherapy , HC FMB , we use a two-dimensional software for determination of isodose curves , however , this software is out of date and frequently becomes inoperable due to the lack of maintenance and it is a closed system without feasibility of interference from computer professionals . This fact requires manual preparation of isodose curves , which are subject to uncertainties due to the subjectivity in the clinical interpretation of medical radiation oncologist and medical physicist responsible for planning , plus dispendiar significant calculation time . The choice of the optimal isodose curve depends on the energy of the radiation beam , the geometry and dimensions of the irradiated area . The contours of the breast studied in this work evaluations showed that , for a given energy input , such as the energy of 1.25 MeV of gamma radiation Unit Telecobaltoterapia , the determination of the percentage depth dose ( PDP ) ...

Evaluating deviations in prostatectomy patients treated with IMRT

Aim - To evaluate the deviations in prostatectomy patients treated with IMRT in order to calculate appropriate margins to create the PTV. Background - Defining inappropriate margins can lead to underdosing in target volumes and also overdosing in healthy tissues, increasing morbidity. Material and methods - 223 CBCT images used for alignment with the CT planning scan based on bony anatomy were analyzed in 12 patients treated with IMRT following prostatectomy. Shifts of CBCT images were recorded in three directions to calculate the required margin to create PTV. Results and discussion - The mean and standard deviation (SD) values in millimetres were −0.05 ± 1.35 in the LR direction, −0.03 ± 0.65 in the SI direction and −0.02 ± 2.05 the AP direction. The systematic error measured in the LR, SI and AP direction were 1.35 mm, 0.65 mm, and 2.05 mm with a random error of 2.07 mm; 1.45 mm and 3.16 mm, resulting in a PTV margin of 4.82 mm; 2.64 mm, and 7.33 mm, respectively. Conclusion - With IGRT we suggest a margin of 5 mm, 3 mm and 8 mm in the LR, SI and AP direction, respectively, to PTV1 and PTV2. Therefore, this study supports an anisotropic margin expansion to the PTV being the largest expansion in the AP direction and lower in SI.

4DCT radiotherapy for NSCLC: A review of planning methods

Purpose To establish whether the use of a passive or active technique of planning target volume (PTV) definition and treatment methods for non-small cell lung cancer (NSCLC) deliver the most effective results. This literature review assesses the advantages and disadvantages in recent studies of each, while assessing the validity of the two approaches for planning and treatment. Methods A systematic review of literature focusing on the planning and treatment of radiation therapy to NSCLC tumours. Different approaches which have been published in recent articles are subjected to critical appraisal in order to determine their relative efficacy. Results Free-breathing (FB) is the optimal method to perform planning scans for patients and departments, as it involves no significant increase in cost, workload or education. Maximum intensity projection (MIP) is the fastest form of delineation, however it is noted to be less accurate than the ten-phase overlap approach for computed tomography (CT). Although gating has proven to reduce margins and facilitate sparing of organs at risk, treatment times can be longer and planning time can be as much as 15 times higher for intensity modulated radiation therapy (IMRT). This raises issues with patient comfort and stabilisation, impacting on the chance of geometric miss. Stereotactic treatments can take up to 3 hours to treat, along with increases in planning and treatment, as well as the additional hardware, software and training required. Conclusion Four-dimensional computed tomography (4DCT) is superior to 3DCT, with the passive FB approach for PTV delineation and treatment optimal. Departments should use a combination of MIP with visual confirmation ensuring coverage for stage 1 disease. Stages 2-3 should be delineated using ten-phases overlaid. Stereotactic and gated treatments for early stage disease should be used accordingly; FB-IMRT is optimal for latter stage disease.

The automation of radiotherapy treatment planning assessment

Aim The assessment of treatment plans is an important component in the education of radiation therapists. The establishment of a grade for a plan is currently based on subjective assessment of a range of criteria. The automation of assessment could provide a number of advantages including faster feedback, reduced chance of human error, and simpler aggregation of past results. Method A collection of treatments planned by a cohort of 27 second year radiation therapy students were selected for quantitative evaluation. Treatment sites included the bladder, cervix, larynx, parotid and prostate, although only the larynx plans had been assessed in detail. The plans were designed with the Pinnacle system and exported using the DICOM framework. Assessment criteria included beam arrangement optimisation, volume contouring, target dose coverage and homogeneity, and organ-at-risk sparing. The in-house Treatment and Dose Assessor (TADA) software1 was evaluated for suitability in assisting with the quantitative assessment of these plans. Dose volume data were exported in per-student and per-structure data tables, along with beam complexity metrics, dose volume histograms, and reports on naming conventions. Results The treatment plans were exported and processed using TADA, with the processing of all 27 plans for each treatment site taking less than two minutes. Naming conventions were successfully checked against a reference protocol. Significant variations between student plans were found. Correlation with assessment feedback was established for the larynx plans. Conclusion The data generated could be used to inform the selection of future assessment criteria, monitor student development, and provide useful feedback to the students. The provision of objective, quantitative evaluations of plan quality would be a valuable addition to not only radiotherapy education programmes but also for staff development and potentially credentialing methods. New functionality within TADA developed for this work could be applied clinically to, for example, evaluate protocol compliance.

A dosimetric retrospective planning study comparing volumetric arc therapy (VMAT) and stereotactic body radiotherapy (SBRT) treatment plans for non-small cell lung cancer (NSCLC)

Purpose A retrospective planning study comparing volumetric arc therapy (VMAT) and stereotactic body radiotherapy (SBRT) treatment plans for non-small cell lung cancer (NSCLC). Methods and materials Five randomly selected early stage lung cancer patients were included in the study. For each patient, four plans were created: the SBRT plan and three VMAT plans using different optimisation methodologies. A total of 20 different plans were evaluated. The dose parameters of dose conformity results and the target dose constraints results were compared for these plans. Results The mean planning target volume (PTV) for all the plans (SBRT and VMAT) was 18·3 cm3, with a range from 15·6 to 20·1 cm3. The maximum dose tolerance to 1 cc of all the plans was within 140% (84 Gy) of the prescribed dose, and 95% of the PTV of all the plans received 100% of the prescribed dose (60 Gy). In all the plans, 99% of the PTV received a dose >90% of the prescribed dose, and the mean dose in all the plans ranged from 67 to 72 Gy. The planning target dose conformity for the SBRT and the VMAT (0°, 15° collimator single arc plans and dual arc) plans showed the tightness of the prescription isodose conformity to the target. Conclusions SBRT and VMAT are radiotherapy approaches that increase doses to small tumour targets without increasing doses to the organs at risk. Although VMAT offers an alternative to SBRT for NSCLC and the potential advantage of VMAT is the reduced treatment times over SBRT, the statistical results show that there was no significant difference between the SBRT and VMAT optimised plans in terms of dose conformity and organ-at-risk sparing.

Conventional 3D staging PET/CT in CT simulation for lung cancer: impact of rigid and deformable target volume alignments for radiotherapy treatment planning

Objective: Positron emission tomography (PET)/CT scans can improve target definition in radiotherapy for non-small cell lung cancer (NSCLC). As staging PET/CT scans are increasingly available, we evaluated different methods for co-registration of staging PET/CT data to radiotherapy simulation (RTP) scans.

Methods: 10 patients underwent staging PET/CT followed by RTP PET/CT. On both scans, gross tumour volumes (GTVs) were delineated using CT (GTVCT) and PET display settings. Four PET-based contours (manual delineation, two threshold methods and a source-to-background ratio method) were delineated. The CT component of the staging scan was co-registered using both rigid and deformable techniques to the CT component of RTP PET/CT. Subsequently rigid registration and deformation warps were used to transfer PET and CT contours from the staging scan to the RTP scan. Dice’s similarity coefficient (DSC) was used to assess the registration accuracy of staging-based GTVs following both registration methods with the GTVs delineated on the RTP PET/CT scan.

Results: When the GTVCT delineated on the staging scan after both rigid registration and deformation was compared with the GTVCT on the RTP scan, a significant improvement in overlap (registration) using deformation was observed (mean DSC 0.66 for rigid registration and 0.82 for deformable registration, p50.008). A similar comparison for PET contours revealed no significant improvement in overlap with the use of deformable registration.

Conclusions: No consistent improvements in similarity measures were observed when deformable registration was used for transferring PET-based contours from a staging PET/CT. This suggests that currently the use of rigid registration remains the most appropriate method for RTP in NSCLC.

Assessing the image quality of pelvic MR images acquired with a flat couch for radiotherapy treatment planning

Objectives: To improve the integration of MRI with radiotherapy treatment planning, our department fabricated a flat couch top for our MR scanner. Setting up using this couch top meant that the patients were physically higher up in the scanner and, posteriorly, a gap was introduced between the patient and radiofrequency coil.

The Impact of Colleague Peer Review on the Radiotherapy Treatment Planning Process in the Radical Treatment of Lung Cancer

AIMS: Modern radiotherapy uses techniques to reliably identify tumour and reduce target volume margins. However, this can potentially lead to an increased risk of geographic miss. One source of error is the accuracy of target volume delineation (TVD). Colleague peer review (CPR) of all curative-intent lung cancer plans has been mandatory in our institution since May 2013. At least two clinical oncologists review plans, checking treatment paradigm, TVD, prescription dose tumour and critical organ tolerances. We report the impact of CPR in our institution.

MATERIALS AND METHODS: Radiotherapy treatment plans of all patients receiving radical radiotherapy were presented at weekly CPR meetings after their target volumes were reviewed and signed off by the treating consultant. All cases and any resultant change to TVD (including organs at risk) or treatment intent were recorded in our prospective CPR database. The impact of CPR over a 13 month period from May 2013 to June 2014 is reported.

RESULTS: One hundred and twenty-two patients (63% non-small cell lung carcinoma, 17% small cell lung carcinoma and 20% 'clinical diagnosis') were analysed. On average, 3.2 cases were discussed per meeting (range 1-8). CPR resulted in a change in treatment paradigm in 3% (one patient proceeded to induction chemotherapy, two patients had high-dose palliative radiotherapy). Twenty-one (17%) had a change in TVD and one (1%) patient had a change in dose prescription. In total, 6% of patients had plan adjustment after review of dose volume histogram.

CONCLUSION: The introduction of CPR in our centre has resulted in a change in a component of the treatment plan for 27% of patients receiving curative-intent lung radiotherapy. We recommend CPR as a mandatory quality assurance step in the planning process of all radical lung plans.

Comparison of monte carlo collimator transport methods for photon treatment planning in radiotherapy

The aim of this work was a Monte Carlo (MC) based investigation of the impact of different radiation transport methods in collimators of a linear accelerator on photon beam characteristics, dose distributions, and efficiency. Thereby it is investigated if it is possible to use different simplifications in the radiation transport for some clinical situations in order to save calculation time.