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.

The Impact of Frailty Screening on Radiation Treatment Modification.

BACKGROUND: Care overburden makes it difficult to perform comprehensive geriatric assessments (CGAs) in oncology settings. We analyzed if screening tools modified radiotherapy in oncogeriatric patients. METHODS: Patients ≥ 65 years, irradiated between December 2020 and March 2021 at the Hospital Provincial de Castellón, completed the frailty G8 and estimated survival Charlson questionnaires. The cohort was stratified between G8 score ≤ 14 (fragile) or >14 (robust); the cutoff point for the Charlson index was established at five. RESULTS: Of 161 patients; 69.4% were male, the median age was 75 years (range 65-91), and the prevailing performance status (PS) was 0-1 (83.1%). Overall, 28.7% of the cohort were frail based on G8 scores, while the estimated survival at 10 years was 2.25% based on the Charlson test. The treatment administered changed up to 21% after frailty analysis. The therapies prescribed were 5.8 times more likely to be modified in frail patients based on the G8 test. In addition, patients ≥ 85 years (p = 0.01), a PS ≥ 2 (p = 0.008), and limited mobility (p = 0.024) were also associated with a potential change. CONCLUSIONS: CGAs remain the optimal assessment tool in oncogeriatry. However, we found that the G8 fragility screening test, which is easier to integrate into patient consultations, is a reliable and efficient aid to rapid decision making.

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.

Intraoperative radiation therapy (IORT) for soft tissue sarcoma - ESTRO IORT Task Force/ACROP recommendations.

PURPOSE: To describe guidelines for the use of intraoperative radiation therapy (IORT) in the treatment of soft-tissue sarcomas (STS). METHODS: A panel of experts in the field performed a systematic literature review, supplemented their clinical experience and developed recommendations for the use of IORT in the treatment of STS. RESULTS: Based on the evidence from the systematic literature review and the clinical experience of the panel members, recommendations regarding patient selection, incorporation into multimodal treatment concepts and the IORT procedure itself are made. The rationale for IORT in extremity and retroperitoneal STS is summarized and results of the major series in terms of patient and treatment characteristics, oncological outcome and toxicity are presented. We define surgical factors, volumes for irradiation, technical requirements, dose prescription, recording and reporting, treatment delivery and care during the course of IORT covering the main IORT techniques used for the treatment of STS. In extremity STS, evidence originates from a few small prospective and mainly from retrospective single centre studies. Based on those reports, IORT containing-approaches result in very high local control rates with low rates of acute and late toxicity. In retroperitoneal sarcomas, evidence is derived from one prospective randomized trial, a few prospective and a large number of retrospective studies. The randomized trial compared IORT combined with moderate doses of postoperative external-beam radiation therapy (EBRT) to high-dose postoperative EBRT alone after gross total resection, clearly favouring the IORT-containing approach. These results have been confirmed by the prospective and retrospective studies, which similarly showed high local control rates with acceptable toxicity, mainly favouring combinations of preoperative EBRT and IORT. CONCLUSIONS: IORT-containing approaches result in high rates of local control with low to acceptable toxicity rates. Based on the available evidence, we made recommendations for the use of IORT in STS. Clinicians and researchers are encouraged to use these guidelines in clinical routine as well as in the design of future trials.

Radiotherapy for metastatic spinal cord compression with increased radiation doses (RAMSES-01): a prospective multicenter study.

BACKGROUND: Patients with metastatic spinal cord compression (MSCC) and favorable survival prognoses can benefit from radiation doses greater than 30Gy in 10 fractions in terms of improved local progression-free survival (LPFS) and overall survival (OS). METHODS/DESIGN: This prospective study mainly investigates LPFS after precision radiotherapy (volumetric modulated arc therapy or stereotactic body radiotherapy) with 18 × 2.33Gy in 3.5 weeks. LPFS is defined as freedom from progression of motor deficits during radiotherapy and an in-field recurrence of MSCC following radiotherapy. The maximum relative dose allowed to the spinal cord is 101.5% of the prescribed dose, resulting in an equivalent dose in 2Gy-fractions (EQD2) for radiation myelopathy is 45.5Gy, which is below the tolerance dose of 50Gy according to the Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC). The EQD2 of this regimen for tumor cell kill is 43.1Gy, which is 33% higher than for 30Gy in 10 fractions (EQD2 = 32.5Gy). Primary endpoint is LPFS at 12 months after radiotherapy. Secondary endpoints include the effect of 18 × 2.33Gy on motor function, ambulatory status, sensory function, sphincter dysfunction, LPFS at other follow-up times, overall survival, pain relief, relief of distress and toxicity. Follow-up visits for all endpoints will be performed directly and at 1, 3, 6, 9 and 12 months after radiotherapy. A total of 65 patients are required for the prospective part of the study. These patients will be compared to a historical control group of at least 235 patients receiving conventional radiotherapy with 10x3Gy in 2 weeks. DISCUSSION: If precision radiotherapy with 18 × 2.33Gy results in significantly better LPFS than 10x3Gy of conventional radiotherapy, this regimen should be strongly considered for patients with MSCC and favorable survival prognoses. TRIAL REGISTRATION: Clinicaltrials.gov NCT04043156. Registered 30-07-2019.

Patient-Reported Outcomes-Secondary Analysis of the SCORE-2 Trial Comparing 4 Gy × 5 to 3 Gy × 10 for Metastatic Epidural Spinal Cord Compression.

PURPOSE: To compare 4 Gy × 5 (1 week) to 3 Gy × 10 (2 weeks) in relieving pain and distress in patients with metastatic epidural spinal cord compression (MESCC). METHODS AND MATERIALS: The randomized SCORE-2 trial compared 4 Gy × 5 (n = 101) to 3 Gy × 10 (n = 102) for MESCC. In this additional analysis, these regimens were compared for their effect in relieving pain and distress. Distress was evaluated with the distress-thermometer (0 = no distress, 10 = extreme distress) and pain on a linear scale (0 = no pain, 10 = worst pain). Relief of distress was defined as decrease of ≥2 points; complete and partial pain relief were defined as achieving a score of 0 points and a decrease ≥2 points, respectively, without increase of analgesic use. This prospective secondary analysis of the SCORE-2 trial aimed to show that 4 Gy × 5 was not inferior to 3 Gy × 10 regarding distress and pain relief. Analyses were performed using the unconditional test of noninferiority for binomial differences based on restricted maximum likelihood estimates (noninferiority margin: -20%). Evaluations were performed before, directly after, and 1, 3, and 6 months after radiation therapy. (ClinicalTrials.gov: NCT02189473). RESULTS: At baseline, median distress scores were 8 (2-10) points in the 4 Gy × 5 group and 8 (2-10) points in the 3 Gy × 10 group. At 1 month, distress relief rates were 58.1% (43/74) and 62.7% (47/75) (difference: -4.6%; 95% confidence interval, -20.0% to +11.1%; P = .025). At baseline, median pain scores were 7 (2-10) and 7 (2-10) points, respectively. At 1 month, complete pain relief rates were 23.5% (16/68) versus 20.0% (14/70) (difference, +3.5%; 95% confidence interval, -10.4% to +17.5%; P < .001), and overall pain relief rates were 52.9% (36/68) versus 57.1% (40/70) (difference, -4.2%; 95% confidence interval, -20.5% to +12.3%; P = .029). Distress and pain relief rates after 4 Gy × 5 were largely comparable to 3 Gy × 10 at all time points. Associated 95% confidence intervals did not point toward any relevant differences. CONCLUSIONS: In patients with MESCC and poor to intermediate survival prognoses, 4 Gy × 5 appeared noninferior to 3 Gy × 10 regarding pain and distress relief.

Real-life management of patients with breakthrough cancer pain caused by bone metastases in Spain.

Purpose: We aimed to explore the characteristics, and real-life therapeutic management of patients with breakthrough cancer pain (BTcP) caused by bone metastases in Spain, and to evaluate physicians' opinion of and satisfaction with prescribed BTcP therapy. Participants and methods: For the purposes of this study, an ad-hoc questionnaire was developed consisting of two domains: a) organizational aspects and care standards; b) clinical and treatment variables of bone metastatic BTcP patients. In addition, physicians' satisfaction with their prescribed BTcP therapy was assessed. Specialists collected data from up to five patients receiving treatment for BTcP caused by bone metastasis, all patients gave their consent to participate prior to inclusion. Results: A total of 103 cancer pain specialists (radiation oncologists [38.8%], pain specialists [33.0%], and palliative care (PC) specialists [21.4%]) were polled, and data on 386 BTcP patients with bone metastatic disease were collected. Only 33% of the specialists had implemented specific protocols for BTcP management, and 19.4% had established referral protocols for this group of patients. Half of all participants (50.5%) address quality of life and quality of care in their patients; however, only 27.0% did so from the patient's perspective, as they should do. Most patients had multiple metastases and were prescribed rapid-onset fentanyl preparations (71.2%), followed by immediate-release morphine (9.3%) for the treatment of BTcP. Rapid-onset fentanyl was prescribed more often in PC units (79.0%) than in pain units (75.9%) and radiation oncology units (61.1%) (p<0.01). Furthermore, most physicians (71.8%) were satisfied with the BTcP therapy prescribed. Conclusions: Our results demonstrate the need for routine assessment of quality of life in patients with bone BTcP. These findings also underscore the necessity for a multidisciplinary therapeutic strategy for breakthrough pain in clinical practice in Spain.

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.

Statistical process control for electron beam monitoring.

PURPOSE: To assess the electron beam monitoring statistical process control (SPC) in linear accelerator (linac) daily quality control. We present a long-term record of our measurements and evaluate which SPC-led conditions are feasible for maintaining control. METHODS: We retrieved our linac beam calibration, symmetry, and flatness daily records for all electron beam energies from January 2008 to December 2013, and retrospectively studied how SPC could have been applied and which of its features could be used in the future. A set of adjustment interventions designed to maintain these parameters under control was also simulated. RESULTS: All phase I data was under control. The dose plots were characterized by rising trends followed by steep drops caused by our attempts to re-center the linac beam calibration. Where flatness and symmetry trends were detected they were less-well defined. The process capability ratios ranged from 1.6 to 9.3 at a 2% specification level. Simulated interventions ranged from 2% to 34% of the total number of measurement sessions. We also noted that if prospective SPC had been applied it would have met quality control specifications. CONCLUSIONS: SPC can be used to assess the inherent variability of our electron beam monitoring system. It can also indicate whether a process is capable of maintaining electron parameters under control with respect to established specifications by using a daily checking device, but this is not practical unless a method to establish direct feedback from the device to the linac can be devised.

Fractionated stereotactic radiotherapy plus bevacizumab after response to bevacizumab plus irinotecan as a rescue treatment for high-grade gliomas.

AIM: To evaluate the possibility of implementing a new scheme of rescue treatment after relapse or progression of high-grade glioma (HGG) treated at the first-line with bevacizumab and irinotecan (BVZ+CPT11), evaluating the response and toxicity of associating BVZ and fractionated stereotactic radiotherapy (BVZ+FSRT). MATERIALS AND METHODS: We retrospectively analysed data from 59 patients with relapse of HGG. Nine patients with HGG relapse after treatment using the Stupp protocol that were treated with BVZ+CPT11 for progression between July 2007 and August 2012, after which the response was assessed according to the Revised Assessment in Neuro-Oncology (RANO) criteria. BVZ was administered at a dose of 10 mg/kg and FSRT up to a prescribed dose of 30 Gy, 500 cGy per fraction, three days a week. The median follow-up was 38 months. RESULTS: The treatment was well-tolerated by all patients. The response after nuclear magnetic resonance imaging (MRI) at 3-6 months was progression in two patients, stable disease in four, and three patients had a partial response. The median overall survival (OS) from diagnosis until death or the last control was 36.8 months. The median progression-free survival (PFS) was 10.8 months. The results from tumour sub-group analysis indicated that the PFS was not statistically significant although it seemed that it was higher in grade-III. The OS was higher in grade-III gliomas. CONCLUSIONS: The combination of BVZ+FSRT as a second-line HGG relapse rescue treatment is well-tolerated and seems to offer promising results. We believe that multi-centre prospective studies are needed to determine the long-term efficacy and toxicity of this therapeutic approach.

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.

Oligometastases in prostate cancer: restaging stage IV cancers and new radiotherapy options.

There are various subgroups of patients with metastatic prostate cancer: polymetastatic, oligometastatic, or oligo-recurrent cancers whose progression follows different courses and for whom there are different treatment options. Knowledge of tumor dissemination pathways and different genetic and epigenetic tumor profiles, as well as their evolution during disease progression, along with new diagnostic and therapeutic advances has allowed us to address these situations with local ablative treatments such as stereotactic body radiation therapy or stereotactic radiosurgery. These treatments provide high rates of local control with low toxicity in metastatic spread for primary cancers including those of pulmonary, digestive, and renal origin, while these types of treatments are still emerging for cancers of prostatic origin. There are several retrospective studies showing the effectiveness of such treatments in prostate cancer metastases, which has led to the emergence of prospective studies on the issue and even some phase II studies intended to prevent or delay systemic treatments such as chemotherapy. Here we collect together and review these past experiences and the studies currently underway. These types of radiotherapy treatments redefine how we approach extracranial metastatic disease and open up new possibilities for combination therapy with new systemic treatment agents.

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.

Adjusting the dose of tamoxifen in patients with early breast cancer and CYP2D6 poor metabolizer phenotype.

BACKGROUND: CYP2D6 is a key enzyme in tamoxifen metabolism, transforming it into its main active metabolite, endoxifen. Poor CYP2D6 metabolizers (PM) have lower endoxifen plasma concentrations and possibly benefit less from treatment with tamoxifen. We evaluated tamoxifen dose adjustment in CYP2D6 PM patients in order to obtain plasma concentrations of endoxifen comparable to patients with extensive CYP2D6 metabolism (EM). PATIENTS AND METHODS: Comprehensive CYP2D6 genotyping and plasma tamoxifen metabolite concentrations were performed among 249 breast cancer patients in adjuvant treatment with tamoxifen. Tamoxifen dose was increased in PM patients to 40 mg and to 60 mg daily for a 4-month period each, repeating tamoxifen metabolite measurements on completion of each dose increase. We compared the endoxifen levels between EM and PM patients, and among the PM patients at each dose level of tamoxifen (20, 40 and 60 mg). RESULTS: Eleven PM patients (4.7%) were identified. The mean baseline endoxifen concentration in EM patients (11.30 ng/ml) was higher compared to the PM patients (2.33 ng/ml; p < 0.001). In relation to the 20 mg dose, increasing the tamoxifen dose to 40 and 60 mg in PM patients significantly raised the endoxifen concentration to 8.38 ng/ml (OR 3.59; p = 0.013) and to 9.30 ng/ml (OR 3.99; p = 0.007), respectively. These concentrations were comparable to those observed in EM patients receiving 20 mg of tamoxifen (p = 0.13 and p = 0.64, respectively). CONCLUSION: In CYP2D6 PM patients, increasing the standard tamoxifen dose two-fold or three-fold raises endoxifen concentrations to levels similar to those of patients with EM phenotype.

The contribution of the cone beam Kv CT (CBKvCT) to the reduction in toxicity of prostate cancer treatment with external 3D radiotherapy.

OBJECTIVE: Show that verification through cone beam Kv CT (CBKvCT) in a series of patients treated with 3D external radiotherapy (3DRT) for prostate cancer (PC) is related to a reduction in acute and late toxicity levels. MATERIALS AND METHOD: A retrospective, non-randomized study of two homogeneous groups of patients treated between 2005 and 2008, 46 were verified using electronic portal devices (EPIDs) and 48 through CBKvCT. They received 3DRT for localized PC (T1-T3N0M0) and were prescribed the same doses. Treatment was simulated and planned with the same criteria with the same equipment with a median follow-up time of 24 months (12-54 months). Urinary and gastrointestinal toxicity was determined using Common Toxicity Criteria scale, version 4 and RTOG scales. Statistical analysis of data was performed where p < 0.005 being significative. RESULTS AND DISCUSSION: With an overall median follow-up time of 24 months, the levels of proctitis were, respectively, 19.56, 15.21 and 15.2 % in the first group, compared with 4.17, 2.08 and 8.33 % in the second. Statistically, less total and late proctitis, late rectal bleeding, anal fissure, total and acute haematuria, total and acute urinary frequency and total urinary incontinence was observed. No statistically significant evidence of a lowering in toxicity neither in terms of acute and late dysuria nor of a relationship to the TNM, Gleason or PSA or in the grade of stability. CONCLUSION: Verification through CBKvCT in this series is associated with a statistically significant lowering toxicity. This justifies its use. Greater monitoring would be necessary to assess the impact of verification at the level of biochemical control.

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.