Prostate Region-Wise Imaging Biomarker Profiles for Risk Stratification and Biochemical Recurrence Prediction.

BACKGROUND: Identifying prostate cancer (PCa) patients with a worse prognosis and a higher risk of biochemical recurrence (BCR) is essential to guide treatment choices. Here, we aimed to identify possible imaging biomarker (perfusion/diffusion + radiomic features) profiles extracted from MRIs that were able to discriminate patients according to their risk or the occurrence of BCR 10 years after diagnosis, as well as to evaluate their predictive value with or without clinical data. METHODS: Patients with localized PCa receiving neoadjuvant androgen deprivation therapy and radiotherapy were retrospectively evaluated. Imaging features were extracted from MRIs for each prostate region or for the whole gland. Univariate and multivariate analyses were conducted. RESULTS: 128 patients (mean [range] age, 71 [50-83] years) were included. Prostate region-wise imaging biomarker profiles mainly composed of radiomic features allowed discriminating risk groups and patients experiencing BCR. Heterogeneity-related radiomic features were increased in patients with worse prognosis and with BCR. Overall, imaging biomarkers profiles retained good predictive ability (AUC values superior to 0.725 in most cases), which generally improved when clinical data were included (particularly evident for the prediction of the BCR, with AUC values ranging from 0.841 to 0.877 for combined models and sensitivity values above 0.960) and when models were built per prostate region vs. the whole gland. CONCLUSIONS: Prostate region-aware imaging profiles enable identification of patients with worse prognosis and with a higher risk of BCR, retaining higher predictive values when combined with clinical variables.

Bone-only oligometastatic prostate cancer: can SABR improve outcomes? A single-center experience.

PURPOSE: Ablative treatment of oligometastases has shown survival benefit with certain tumors, although these effects still are to be demonstrated in prostate cancer. MATERIALS AND METHODS: We analysed the toxicity and clinical control results obtained in patients with bone-only oligometastatic prostate cancer treated with stereotactic ablative radiotherapy (SABR). Retrospective study on patients with metachronous oligoprogression and synchronous de novo bone-only oligometastatic prostate cancer treated with SABR and androgen deprivation therapy. RESULTS: Treatment schedules varied according to location and organs at risk, with biologically equivalent dose (BED) ≥100 Gy. Fifty-five bone lesions (31 patients) were treated and evaluated for toxicity, local control, progression-free survival (PFS), and overall survival (OS). After a 41-month follow-up, there was minimal acute or chronic toxicity and no G3 toxicity. The local control at 3 and 5 years was 100% and 87.1%, respectively. Median PFS and OS were 43 and 98 months, respectively. The best result in PFS was obtained with BED ≥230 Gy, delaying time to the next systemic therapy by 28.5 months. CONCLUSION: The use of SABR in bone oligometastases of prostate cancer is safe with minimal toxicity and excellent results in local control and PFS, delaying the start of the next systemic therapy.

The Usefulness of Adaptative Radiotherapy in Prostate Cancer: How, When, and Who?

The aim of this study was to develop a deformable image registration (DIR)-based offline ART protocol capable of identifying significant dosimetric changes in the first treatment fractions to determine when adaptive replanning is needed. A total of 240 images (24 planning CT (pCT) and 216 kilovoltage cone-beam CT (CBCT)) were prospectively acquired from 24 patients with prostate adenocarcinoma during the first three weeks of their treatment (76 Gy in 38 fractions). This set of images was used to plan a hypofractionated virtual treatment (57.3 Gy in 15 fractions); correlation with the DIR of pCT and each CBCT allowed to translate planned doses to each CBCT, and finally mapped back to the pCT to compare with those actually administered. In 37.5% of patients, doses administered in 50% of the rectum (D50) would have exceeded the dose limitation to 50% of the rectum (R50). We first observed a significant variation of the planned rectal volume in the CBCTs of fractions 1, 3, and 5. Then, we found a significant relationship between the D50 accumulated in fractions 1, 3, and 5 and the lack of compliance with the R50. Finally, we found that a D50 variation rate [100 × (administered D50 − planned D50/planned D50)] > 1% in fraction three can reliably identify variations in administered doses that will lead to exceeding rectal dose constraint.

Nomogram for the personalisation of radiotherapy treatments in breast cancer patients.

INTRODUCTION: Numerous prospective studies have shown that the incorporation of genomic assays into clinical practice significantly impacts the choice of adjuvant treatments for patients with early-stage breast cancer. However, the same evidence does not exist for the treatment of locoregional recurrences. HYPOTHESIS AND OBJECTIVES: The main objective of this work was to identify the clinicopathological, molecular, and genetic parameters that allow patients to be more precisely categorised into risk groups, in order to create a locoregional recurrence riskclassification tool, the PersonalRT27. MATERIAL AND METHODS: To create PersonalRT27, we retrospective assessed the variables of patients with early breast cancer (stages I or II) who had undergone the OncotypeDx ® and MammaPrint ® genetic tests. These variables and factors included in the tests were categorised and weighted to obtain scores between 1 and 5 pointsto represent a lower or higher risk of relapse, respectively, based on these factors and as determined by the researchers. RESULTS: The mean follow-up time was 60.5 months (range 25-96 months); locoregional progression-free survival at the time of the analysis was 98.4%, and overall survival was 97.5%, of which 0.6% of the deaths had been cancer specific. The area under the curve for the PersonalRT27 was 0.76 (95% CI [0.70, 0.81]), sensitivity was 78%, and the specificity was 58.9%. We used these factors to create an inhospital web-based nomogram. CONCLUSIONS: The PersonalRT27 is a novel tool that integrates clinical-pathological, molecular, and genetic parameters. External and independent validation will be required to implement its clinical use.

Practical issues regarding angular and energy response in in vivo intraoperative electron radiotherapy dosimetry.

AIM: To estimate angular response deviation of MOSFETs in the realm of intraoperative electron radiotherapy (IOERT), review their energy dependence, and propose unambiguous names for detector rotations. BACKGROUND: MOSFETs have been used in IOERT. Movement of the detector, namely rotations, can spoil results. MATERIALS AND METHODS: We propose yaw, pitch, and roll to name the three possible rotations in space, as these unequivocally name aircraft rotations. Reinforced mobile MOSFETs (model TN-502RDM-H) and an Elekta Precise linear accelerator were used. Two detectors were placed in air for the angular response study and the whole set of five detectors was calibrated as usual to evaluate energy dependence. RESULTS: The maximum readout was obtained with a roll of 90° and 4 MeV. With regard to pitch movement, a substantial drop in readout was achieved at 90°. Significant overresponse was measured at 315° with 4 MeV and at 45° with 15 MeV. Energy response is not different for the following groups of energies: 4, 6, and 9 MeV; and 12 MeV, 15 MeV, and 18 MeV. CONCLUSIONS: Our proposal to name MOSFET rotations solves the problem of defining sensor orientations. Angular response could explain lower than expected results when the tip of the detector is lifted due to inadvertent movements. MOSFETs energy response is independent of several energies and differs by a maximum of 3.4% when dependent. This can limit dosimetry errors and makes it possible to calibrate the detectors only once for each group of energies, which saves time and optimizes lifespan of MOSFETs.

Implementation of an intraoperative electron radiotherapy in vivo dosimetry program.

BACKGROUND: Intraoperative electron radiotherapy (IOERT) is a highly selective radiotherapy technique which aims to treat restricted anatomic volumes during oncological surgery and is now the subject of intense re-evaluation. In vivo dosimetry has been recommended for IOERT and has been identified as a risk-reduction intervention in the context of an IOERT risk analysis. Despite reports of fruitful experiences, information about in vivo dosimetry in intraoperative radiotherapy is somewhat scarce. Therefore, the aim of this paper is to report our experience in developing a program of in vivo dosimetry for IOERT, from both multidisciplinary and practical approaches, in a consistent patient series. We also report several current weaknesses. METHODS: Reinforced TN-502RDM-H mobile metal oxide semiconductor field effect transistors (MOSFETs) and Gafchromic MD-55-2 films were used as a redundant in vivo treatment verification system with an Elekta Precise fixed linear accelerator for calibrations and treatments. In vivo dosimetry was performed in 45 patients in cases involving primary tumors or relapses. The most frequent primary tumors were breast (37 %) and colorectal (29 %), and local recurrences among relapses was 83 %. We made 50 attempts to measure with MOSFETs and 48 attempts to measure with films in the treatment zones. The surgical team placed both detectors with supervision from the radiation oncologist and following their instructions. RESULTS: The program was considered an overall success by the different professionals involved. The absorbed doses measured with MOSFETs and films were 93.8 ± 6.7 % and 97.9 ± 9.0 % (mean ± SD) respectively using a scale in which 90 % is the prescribed dose and 100 % is the maximum absorbed dose delivered by the beam. However, in 10 % of cases we experienced dosimetric problems due to detector misalignment, a situation which might be avoided with additional checks. The useful MOSFET lifetime length and the film sterilization procedure should also be controlled. CONCLUSIONS: It is feasible to establish an in vivo dosimetry program for a wide set of locations treated with IOERT using a multidisciplinary approach according to the skills of the professionals present and the detectors used; oncological surgeons' commitment is key to success in this context. Films are more unstable and show higher uncertainty than MOSFETs but are cheaper and are useful and convenient if real-time treatment monitoring is not necessary.

Defining Action Levels for In Vivo Dosimetry in Intraoperative Electron Radiotherapy.

In vivo dosimetry is recommended in intraoperative electron radiotherapy (IOERT). To perform real-time treatment monitoring, action levels (ALs) have to be calculated. Empirical approaches based on observation of samples have been reported previously, however, our aim is to present a predictive model for calculating ALs and to verify their validity with our experimental data. We considered the range of absorbed doses delivered to our detector by means of the percentage depth dose for the electron beams used. Then, we calculated the absorbed dose histograms and convoluted them with detector responses to obtain probability density functions in order to find ALs as certain probability levels. Our in vivo dosimeters were reinforced TN-502RDM-H mobile metal-oxide-semiconductor field-effect transistors (MOSFETs). Our experimental data came from 30 measurements carried out in patients undergoing IOERT for rectal, breast, sarcoma, and pancreas cancers, among others. The prescribed dose to the tumor bed was 90%, and the maximum absorbed dose was 100%. The theoretical mean absorbed dose was 90.3% and the measured mean was 93.9%. Associated confidence intervals at P = .05 were 89.2% and 91.4% and 91.6% and 96.4%, respectively. With regard to individual comparisons between the model and the experiment, 37% of MOSFET measurements lay outside particular ranges defined by the derived ALs. Calculated confidence intervals at P = .05 ranged from 8.6% to 14.7%. The model can describe global results successfully but cannot match all the experimental data reported. In terms of accuracy, this suggests an eventual underestimation of tumor bed bleeding or detector alignment. In terms of precision, it will be necessary to reduce positioning uncertainties for a wide set of location and treatment postures, and more precise detectors will be required. Planning and imaging tools currently under development will play a fundamental role.

Failure mode and effect analysis oriented to risk-reduction interventions in intraoperative electron radiation therapy: the specific impact of patient transportation, automation, and treatment planning availability.

BACKGROUND AND PURPOSE: Industrial companies use failure mode and effect analysis (FMEA) to improve quality. Our objective was to describe an FMEA and subsequent interventions for an automated intraoperative electron radiotherapy (IOERT) procedure with computed tomography simulation, pre-planning, and a fixed conventional linear accelerator. MATERIAL AND METHODS: A process map, an FMEA, and a fault tree analysis are reported. The equipment considered was the radiance treatment planning system (TPS), the Elekta Precise linac, and TN-502RDM-H metal-oxide-semiconductor-field-effect transistor in vivo dosimeters. Computerized order-entry and treatment-automation were also analyzed. RESULTS: Fifty-seven potential modes and effects were identified and classified into 'treatment cancellation' and 'delivering an unintended dose'. They were graded from 'inconvenience' or 'suboptimal treatment' to 'total cancellation' or 'potentially wrong' or 'very wrong administered dose', although these latter effects were never experienced. Risk priority numbers (RPNs) ranged from 3 to 324 and totaled 4804. After interventions such as double checking, interlocking, automation, and structural changes the final total RPN was reduced to 1320. CONCLUSIONS: FMEA is crucial for prioritizing risk-reduction interventions. In a semi-surgical procedure like IOERT double checking has the potential to reduce risk and improve quality. Interlocks and automation should also be implemented to increase the safety of the procedure.

In vivo dosimetry in intraoperative electron radiotherapy: microMOSFETs, radiochromic films and a general-purpose linac.

INTRODUCTION: In vivo dosimetry is desirable for the verification, recording, and eventual correction of treatment in intraoperative electron radiotherapy (IOERT). Our aim is to share our experience of metal oxide semiconductor field-effect transistors (MOSFETs) and radiochromic films with patients undergoing IOERT using a general-purpose linac. MATERIALS AND METHODS: We used MOSFETs inserted into sterile bronchus catheters and radiochromic films that were cut, digitized, and sterilized by means of gas plasma. In all, 59 measurements were taken from 27 patients involving 15 primary tumors (seven breast and eight non-breast tumors) and 12 relapses. Data were subjected to an outliers' analysis and classified according to their compatibility with the relevant doses. Associations were sought regarding the type of detector, breast and non-breast irradiation, and the radiation oncologist's assessment of the difficulty of detector placement. At the same time, 19 measurements were carried out at the tumor bed with both detectors. RESULTS: MOSFET measurements ([Formula: see text] = 93.5 %, sD = 6.5 %) were not significantly shifted from film measurements ([Formula: see text] = 96.0 %, sD = 5.5 %; p = 0.109), and no associations were found (p = 0.526, p = 0.295, and p = 0.501, respectively). As regards measurements performed at the tumor bed with both detectors, MOSFET measurements ([Formula: see text] = 95.0 %, sD = 5.4 % were not significantly shifted from film measurements ([Formula: see text] = 96.4 %, sD = 5.0 %; p = 0.363). CONCLUSION: In vivo dosimetry can produce satisfactory results at every studied location with a general-purpose linac. Detector choice should depend on user factors, not on the detector performance itself. Surgical team collaboration is crucial to success.

PITASOR epidemiological study: prevalence, incidence and treatment of anaemia in radiation therapy oncology departments in Spain.

INTRODUCTION: Anemia is the most common haematological complication in cancer patients. OBJECTIVE: Analysis of the incidence, prevalence and treatment of anemia in oncologic patients treated in Radiation Oncology Departments in Spain (ROD) and monitoring of the existing recommendations for the treatment of anemia. MATERIAL AND METHODS: Observational, prospective, multicenter study which involved 19 Spanish ROD. The study was approved by the CEIC Central Defense Hospital. 477 patients with solid tumors, subsidiary of RT with radical intent referred to such centers within a period of one month (5/5/09 to 5/6/09) and gave their consent to participate in the study. We gathered the main characteristics of patients and their oncologic disease. All patients underwent a determination of Hb levels before RT, upon reaching 25-35 Gy and at the end treatment. In patients with anemia we assessed the existence of related symptoms and its treatment. RESULTS: Basal situation: The prevalence of anemia was 34.8% (166 patients). Mean Hb in patients with anemia was 11.17 ± 1.07 g/dl. Anemia-related symptoms were present in 34% of the patients. Anemia predisposing factors were: stage of the disease, previously received chemotherapy, and hormonal therapy. 39% (66 patients) received anemia treatment, with a mean Hb of 10.43 ± 1.04 g/dl. During RT: The prevalence of anemia was 38.9% (182 patients) with a mean Hb of 11.24 ± 1.21 g/dl. Predisposing factors for anemia during RT treatment were: age, male sex, chemotherapy prior to RT, basal anemia and chemotherapy during RT. 36.3% (66 patients) had anemia-related symptoms. 34.6% (63 patients) with a mean Hb of 10.5 ± 1.37 g/dl received treatment for anemia. The prevalence of anemia at the end of the RT was 38.1% (177 patients) with a mean Hb of 11.19 ± 1.18 g/dl. The predisposing factors for the appearance of anemia at the end of RT were: male sex, anemia at basal situation and during treatment and chemotherapy during RT. 34% (61 patients) had anemia-related symptoms and 73 patients (41.2%) with a mean Hb of 10.5 ± 1.22 g/dl received treatment for anemia. The presence of anemia-related symptoms was significantly correlated with the beginning of treatment for anemia. The incidence of anemia (new cases) during radiotherapy was 17.5%. CONCLUSION: The prevalence of anemia in basal situation, during RT and at the end of RT is 34.8%, 38.9% and 38.1%. During RT the incidence of anemia is 17.5%. 39.8%-41.2% of patients with anemia and 64.2%-68% of patients with anemia-related symptoms received treatment. Treatment of anemia starts with Hb<11 g/dl and the goal is to achieve Hb 12 g/dl. In our Radiotherapy Oncology Departments, the treatment of anemia complies with the current recommendations and guidelines in use.

Contribution of hypoxia-measuring molecular imaging techniques to radiotherapy planning and treatment.

Hypoxia is related to poor prognosis because it is associated to chemo- and radioresistance. During recent years the evolution of imaging methods like PET/CT and MRI has meant the appearance of new perspectives with direct implications in radiation therapy. We discuss previous experiences in staging, planning and in the follow-up process with these techniques for measuring tumour hypoxia.