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- Comparison of different radiotherapy techniques for locally advanced pancreatic tumorsPublication . Gomes, Adriana; Rodrigues, Darlene; Costa Ferreira, BrígidaRadiotherapy (RT) associated with systemic therapy is the standard treatment for Locally Advanced Pancreatic Cancer (LAPC). The aim of this study was to compare the efficacy of different RT techniques using the clinical data reported in the literature. Clinical data was collected from scientific papers searched in the databases PubMed and ScienceDirect. Thirty-four documents published between 1997 and 2015 were found and met the inclusion criteria: locally advanced adenocarcinoma, unresectable and no metastasis. Values of Complete Response (CR), Partial Response (PR), Stable Disease (SD), Pro gression Disease, Progression Free Survival (PFS), and Overall Survival (OS) for Three-Dimensional Conformal Radiation Therapy (3DCRT), Intensity Modulated Radiation Therapy (IMRT) and Stereotactic Body Radiotherapy (SBRT) in the treatment of LAPC were collected. For all RT techniques, Response Rate (RR), defined as the sum of CR and PR, was for 3DCRT 25.2% ± 9.5 [range: 5.0%–49.0%], for IMRT 33.5% ± 10.5 [range: 10.6%–55.6%] and for SBRT 52.2% ± 17.7 [range: 13.3%–69.5%]. For all studied techniques, Local Control (LC), defined as the sum of RR and SD, ranged from 47% to 100%; PFS ranged from 4 to 12 months and OS ranged from 6 to 20 months. A significant improvement in overall response rate was obtained with SBRT compared to 3DRCT and IMRT. However, LC, PFS and OS were similar among the three RT techniques.
- Dose-response to different radiochemotherapy regimens in locally advanced pancreatic cancerPublication . Costa Ferreira, Brígida; Dias, Joana; Gomes, Adriana; Mavroidis, Panayiotis; Rocha, HumbertoConformal radiation therapy (RT) delivered concomitantly with chemotherapy including 5-fluorouracil (5-FU) or Gemcitabine (GEM) is a common treatment for patients with unresectable locally advanced pancreatic tumors. In this study, the Poisson model describing tumor response to these two treatment options was derived. Clinical data was retrieved from reports pub lished from 1990 to 2015. Dosimetric and clinical data from 1196 patients treated with RT with concurrent 5-FU or GEM were gathered. RT doses ranging from 3.6–64.8 Gy, delivered in fractions of 1.2–8 Gy, were converted to a 2 Gy fractionation scheme using the Biological Effective Dose concept. The param eters of the Poisson-Linear-Quadratic-Time model were derived using genetic algorithm optimization to minimize the least-square fitting error and a local search was then made using the maximum likelihood method. The goodness of the fit was assessed using the Pearson v2 -test. For RT+5-FU, D50 was 59.8 Gy, c was 1.3, a/b was 3.2, Tpot was 18.6 days and Tk was 25.0 days. For RT+GEM, D50 was 54.5 Gy, c was 1.4, a/b was 4.6, Tpot was 34.2 days and Tk was 37.2 days. As expected, RT+GEM showed higher efficacy than RT+5-FU. A RT dose-response effect was obtained showing that treatment strategies allowing a dose-escalation in pancreas tumors should be investigated
- Advantage of beam angle optimization in head-and-neck IMRT: Patient specific analysisPublication . Ventura, Tiago; Lopes, Maria do Carmo; Rocha, Humberto; Costa Ferreira, Brígida; Dias, JoanaRadiation therapy (RT) main purpose is to eliminate, in a controlled way, all tumor cells sparing as much as possible the normal tissues. Intensity Modulated Radiation Therapy (IMRT) is becoming the standard treatment technique in RT. Beam angle optimization (BAO) has potential to confer more quality to IMRT inverse planning process compared to manual trial and error approaches. In this study, the BAO advantages in head-and-neck patients are highlighted, using a patient specific analysis. Fluence optimization was done with Erasmus-iCycle multicriterial engine and BAO optimization was performed using two different algorithms: a combinatorial iterative algorithm and an algorithm based on a pattern search method. Plan assessment and comparison was performed with the graphical tool SPIDERplan. Among a set of forty studied nasopharynx cancer cases, three patients have been select for the specific analysis presented in this work. BAO presented plan quality improvements when beam angular optimized plans were compared with the equidistant beam angle solution and when plans based on non-coplanar beams geometries were compared with coplanar arrangements. Improvement in plan quality with a reduced number of beams was also achieved, in one case. For all cases, BAO generated plans with higher target coverage and better sparing of the normal tissues
- Feature selection in small databases: A medical-case studyPublication . Soares, Inês; Dias, Joana; Rocha, Humberto; Lopes, Maria do Carmo; Costa Ferreira, BrigidaPredictions made by using machine learning classification models are recurrent in many research fields for a variety of reasons. In some cases, feature selection can effi- ciently improve the accuracy of classifications, while reducing the computational requirements. However, some predictive studies are characterized by a high dimensionality or based on small datasets.
- Semi-supervised Self-training Approaches in Small and Unbalanced Datasets: Application to Xerostomia Radiation Side-EffectPublication . Soares, Inês; Dias, Joana; Rocha, Humberto; Khouri, Leila; Lopes, Maria do Carmo; Costa Ferreira, BrigidaSupervised learning algorithms have been widely used as predictors and applied in a myriad of studies. The accuracy of the classification algorithms is strongly dependent on the existence of large and balanced training sets. The existence of a reduced number of labeled data can deeply affect the use of supervised approaches. In these cases, semi-supervised learning algorithms can be a way to circumvent the problem.
- Automated Radiotherapy Treatment Planning Using Fuzzy Inference SystemsPublication . Dias, Joana; Rocha, Humberto; Ventura, Tiago; Costa Ferreira, Brigida; Lopes, Maria do CarmoRadiotherapy is one of the treatments available for cancer patients, aiming to irradiate the tumor while preserving healthy structures. The planning of a treatment is a lengthy trial and error procedure, where treatment parameters are iteratively changed and the delivered dose is calculated to see whether it complies with the desired medical prescription. In this paper, a procedure based on fuzzy inference systems (FIS) for automated treatment planning is developed, allowing the calculation of high quality treatment plans without requiring human intervention. The procedure is structured in two different phases, incorporating the automatic selection of the best set of equidistant beam irradiation directions by an enumeration procedure. The developed method is extensively tested using ten head-and-neck cancer cases.
- A heuristic based on fuzzy inference systems for multiobjective IMRT treatment planningPublication . Dias, Joana; Rocha, Humberto; Ventura, Tiago; Costa Ferreira, Brigida; Lopes, Maria do CarmoRadiotherapy is one of the treatments used against cancer. Each treatment has to be planned considering the medical prescription for each specific patient and the information contained in the patient’s medical images. The medical prescription usually is composed by a set of dosimetry constraints, imposing maximum or minimum radiation doses that should be satisfied. Treatment planning is a trial-and-error time consuming process, where the planner has to tune several parameters (like weights and bounds) until an admissible plan is found. Radiotherapy treatment planning can be interpreted as a multiobjective optimization problem, because besides the set of dosimetry constraints there are also several conflicting objectives: maximizing the dose deposited in the volumes to treat and, at the same time, minimizing the dose delivered to healthy cells. In this paper we present a new multiobjective optimization procedure that will, in an automated way, calculate a set of potential non-dominated treatment plans. It is also possible to consider an interactive procedure whenever the planner wants to explore new regions in the non-dominated frontier. The optimization procedure is based on fuzzy inference systems. The new methodology is described and it is applied to a head-and-neck cancer case.
- Comparison of Combinatorial and Continuous Frameworks for the Beam Angle Optimization Problem in IMRTPublication . Rocha, Humberto; Dias, Joana; Ventura, Tiago; Costa Ferreira, Brigida; do Carmo Lopes, MariaRadiation therapy (RT) is used nowadays for the majority of cancer patients. A technologically advanced type of RT is IMRT – intensity-modulated radiation therapy. With this RT modality the cancerous cells of the patient can be irradiated using non-uniform radiation maps delivered from different beam directions. Although non-uniform radiation maps allow, by themselves, an enhanced sparing of the neighboring healthy organs while properly irradiating the tumor with the prescribed dose, selection of appropriate irradiation directions play a decisive role on these conflicting tasks: deliver dose to the tumor while preventing (too much) dose to be deposited in the surrounding tissues. This paper focus on the problem of choosing the best set of irradiation directions, known as beam angle optimization (BAO) problem. Two completely different mathematical formulations of this problem can be found in the literature. A combinatorial formulation, widely used and addressed by many different algorithms and strategies, and a continuous formulation proposed by the authors and addressed by derivative-free algorithms. In this paper, a comparison of two of the most successful strategies to address each one of these formulations is done resorting to a set of ten clinical nasopharyngeal tumor cases already treated at the Portuguese Institute of Oncology of Coimbra.
- Incorporating the Local Biological Effect of Dose Per Fraction in IMRT Inverse OptimizationPublication . BC Ferreira; Mavroidis, Panayiotis; Dias, Joana; Rocha, Humberton intensity modulated radiation therapy (IMRT), the dose in each voxel of the organs at risk (OAR) can be strongly reduced compared to conformal radiation therapy (RT). Due to the sensitivity of late side-effects to fraction size, a smaller dose per fraction in the normal tissues represent an increased tolerance to RT. This expected reduction in biological effect may then be used as an additional degree of freedom during IMRT optimization. In this study, the comparison between plans optimized with and without a voxel-based fractionation correction was made. Four patients diagnosed with a head and neck (HN), a breast, a lung or a prostate tumor were used as test cases. Voxel-based fractionation corrections were incorporated into the optimization algorithm by converting the dose in each normal tissue voxel to EQD2 (equivalent dose delivered at 2 Gy per fraction). The maximum gain in the probability of tumor control (PB), due to the incorporation of the correction for fractionation in each voxel, was 1.3% with a 0.1% increase in the probability of complications (PI) for the HN tumor case. However, in plan optimization and evaluation, when tolerance doses were compared with the respective planned EQD2 (calculated from the 3-dimensional dose distribution), PB increased by 19.3% in the HN, 12.5% in the lung, 6.2% in the breast and 2.7% in the prostate tumor case, respectively. The corresponding increases in PI were 2.3%, 6.2%, 1.0% and 0.7%, respectively. Incorporating voxel-based fractionation corrections in plan optimization is important to be able to show the clinical quality of a given plan against established tolerance constraints. To properly compare different plans, their dose distributions should be converted to a common fractionation scheme (e.g. 2 Gy per fraction) for which the doses have been associated with clinical outcomes.