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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.

Objective: Breakthrough cancer pain (BTcP) is still underestimated and a percentage of patients are not adequately treated, affecting their quality of life. The aim of this review was to generate a series of expert recommendations based on clinical experience and current scientifi c data on the management of BTcP.

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

Contains fulltext : 193640.pdf (Publisher’s version ) (Open Access) BACKGROUND: Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis. METHODS: We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death. RESULTS: A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P

Purpose/Objective(s) SBRT-SG 05 is a collaborative (SBRT-SG, GICOR and SEOR) prospective multicenter phase II trial testing SBRT and androgen deprivation therapy (ADT) in oligorecurrent prostate cancer patients. Materials/Methods Prostate cancer patients (hormone-sensitive or castration-resistant) in an oligorecurrent stage defined as less than 5 bone or lymph node metastases by Choline PET-CT or/and WB-DWI-MRI, after primary treatment, were assigned to receive ADT and SBRT (Vertebral metastases: 1 × 16-18Gy or 3 × 8-9Gy; lymph node metastases: 3 × 10-11 Gy or 6 × 7,5Gy; non-spinal bone metastases: 1 × 16Gy or 3 × 10Gy). Inclusion criteria included: more than 1 year from primary treatment to biochemical recurrence and PSA doubling time greater than 2 months. A minimum of 24 months of LhRh analogues from the time of the enrollment was required and concomitant treatment with chemotherapy, abiraterone or enzalutamide was not allowed. Oncologic outcomes defined by PCWG3 were evaluated separately for hormone-sensitive and castration-resistant patients, using Kaplan-Meier competing risks, and Cox regression. Toxicity was prospectively evaluated according to CTCAE.v4 criteria. Results From 07/2014 to 12/2019, 81 patients from 14 Spanish centers were recruited with a total of 117 oligometastases treated, 67 in lymph nodes, 43 in non-‐spinal bones and 7 in spinal bones. 14 patients were recruited in a castration-resistance status. Median follow-up was 41 months, (range 18 - 72 months). 13 hormone-sensitive (19,4%) and 8 castration-resistant (57,1%) oligorecurrent patients presented distant disease progression. Median distant progression-free survival (DPFS) was 54,2 months (IC95% = 48,2 – 60,3). 18 of the patients who progressed (85,7%) were treated with SBRT for the new lesions, 7 of them presented a subsequent distant progression (38,9%), with a median of second DPFS of 24,4 months (95% CI = 23,7 – 25,2). In the castration resistant subgroup, median DPFS was 33,5 months (range 14,8 – 52,1), 42,9% of them were free from distant disease progression at last follow-up, without the need to start second generation hormonal treatment. Tolerance and toxicity profiles were excellent, none of the patients developed toxicity ≥G3 or symptoms related to local progression of the disease. Conclusion Combination of SBRT and ADT is a safe treatment approach with favorable clinical outcomes for hormone-sensitive and castration-resistant prostate cancer patients. Validation studies are needed in castration-resistant patients. ClinicalTrials.gov Identifier: NCT02192788

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.

Càncer de pròstata resistent a la castració; Oncologia de les radiacions; Consens Cáncer de próstata resistente a la castración; Oncología radioterápica; Consenso Castration-resistant prostate cancer; Radiation oncology; Consensus Background: The knowledge in the field of castration-resistant prostate cancer (CRPC) is developing rapidly, with emerging new therapies and advances in imaging. Nonetheless, in multiple areas there is still a lack of or very limited evidence, and clear guidance from clinicians regarding optimal strategy is required. Methods: A modified Delphi method, with 116 relevant questions divided into 7 different CRPC management topics, was used to develop a consensus statement by the URONCOR group. Results: A strong consensus or unanimity was reached on 93% of the proposed questions. The seven topics addressed were: CRPC definition, symptomatic patients, diagnosis of metastasis, CRPC progression, M0 management, M1 management and sequencing therapy, and treatment monitoring. Conclusions: The recommendations based on the radiation oncology experts' opinions are intended to provide cancer specialists with expert guidance and to standardise CRPC patient management in Spain, facilitating decision-making in different clinically relevant issues regarding CRPC patients.

5024 Background: PSA value is widely used for the monitoring of treatment outcome in mCRPC in the clinical real-world setting. Early PSA changes are not considered in the definition of PSAProg due to the potential for spurious “flare” reactions. We aimed to evaluate the significance of an early PSA increase in mCRPC patients (pts) treated with enzalutamide or abiraterone (Enz/Abi). Methods: We retrospectively evaluated Enz/Abi-treated mCRPC pts from 11 hospitals between 2011-2020. Early PSAProg was defined as a 25% increase in PSA from baseline at 4 (PSAProg4) or 8 (PSAProg8) weeks after treatment initiation. PSA progression at 12 weeks (PSAProg12) was confirmed by a second reading. Uni- and multivariable (MV) Cox regression models were conducted to explore the association of PSAProg and overall survival (OS) in chemotherapy naïve patients treated with Abi or Enz. Interaction tests were conducted to explore differences in the impact of PSA progression on OS in Abi or Enz-treated pts. Results: We analyzed 511 chemotherapy-naïve mCRPC pts treated with Abi (N=391; 76.5%) or Enz (N=120; 23.5%). Median follow-up: 30.2 months. OS was longer in Enz-treated pts (38.1 vs 29m; HR 1.4; p=0.027). 59 (15.1%), 70 (17.9%) and 48 (12.3%) of Abi-treated and 9 (7.5%), 11 (9.2%) and 10 (8.3%) of Enz-treated pts experienced PSAProg4, PSAProg8 and PSAProg12, respectively, although differences were not statistically significant. PSAProg was associated with worse OS at all 3 timepoints only in Abi-treated pts. In Enz-treated pts, PSAProg4 had a large impact on OS, not observed in PSAProg8 or PSAProg12. We observed no significant interaction between agent (Enz/Abi) and PSA progression (Table). Conclusions: PSA progression at 4 weeks after Enz/Abi is significantly associated with shorter OS and may help identify pts not benefitting from Abi/Enz before clinical or radiographic progression. PSA pattern progression and its association with OS might differ depending on the drug used (Enz/Abi). Prospective validation studies are needed.[Table: see text]

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.

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).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).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.In patients with MESCC and poor to intermediate survival prognoses, 4 Gy × 5 appeared noninferior to 3 Gy × 10 regarding pain and distress relief.

Malignant degeneration on pilonidal cyst is an infrequent entity: less than 70 cases have been described in the literature. Predominantly in males around 50-60. Very slow evolution until its malignancy. Predilection for the sacrococcygeal area and epidermoid histology. Infrequent distant dissemination despite the important local extension of the primary tumor. Similar morphological and histological characteristics to anal carcinomas, using schemes of treatment based on radiotherapy and chemotherapy with radical intention according to locoregional and distance extension, associating subsequent surgery depending on the response. We describe a case of this pathology and its therapeutic management based on the literature review available. We present the case of a 70-year-old man with a pilonidal cyst malignancy in the sacrococcygeal region. Locally advanced and unresectable disease at diagnosis with skin, muscle, lymphatic and bone involvement. Pathological confirmation diagnosis established after thick needle biopsy, with a well-differentiated squamous cell carcinoma. It was decided to administer chemotherapy and radiotherapy treatment and, depending on the response evaluated by nuclear magnetic resonance, excision and/or intraoperative radiotherapy in the area of microscopic risk disease. In a second time, reconstruction using glute flaps. Early diagnosis and treatment are essential to improve the unfortunate prognosis. Surgery with curative intention is the standard of care according to locoregional extension in association with radiotherapy and chemotherapy if adverse factors or unresectable disease. In order to enhance local control, dose has been scaled allowing, besides, to minimize the acute toxicity derived from the treatment.

To determine the effectiveness of whole-body diffusion-weighted magnetic resonance imaging (WB-DW-MRI) in detecting metastases by comparing the results with those from choline-positron emission tomography-computed tomography (choline-PET/CT) in patients with biochemical relapse after primary treatment, and no metastases in bone scintigraphy, CT and/or pelvic MRI, or metastatic/oligometastatic prostate cancer (PCa). Patients with this disease profile who could benefit from treatment with stereotactic body radiation therapy (SBRT) were selected and their responses to these techniques were rated. This was a prospective, controlled, unicentric study, involving 46 consecutive patients from our centre who presented biochemical relapse after adjuvant, salvage or radical treatment with external beam radiotherapy, or brachytherapy. After initial tests (bone scintigraphy, CT, pelvic MRI), 35 patients with oligometastases or without them were selected. 11 patients with multiple metastases were excluded from the study. WB-DW-MRI and choline-PET/CT was then performed on each patient within 1 week. The results were interpreted by specialists in nuclear medicine and MRI. If they were candidates for treatment with ablative SBRT (SABR), they were then evaluated every three months with both tests. Choline-PET/CT detected lesions in 16 patients that were not observable using WB-DW-MRI. The results were consistent in seven patients and in three cases, a lesion was observed using WB-DW-MRI that was not detected with choline-PET/CT. The Kappa value obtained was 0.133 (p = 0.089); the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of WB-DW-MRI were estimated at 44.93, 64.29, 86.11, and 19.15%, respectively. For choline-PET/CT patients, the sensitivity, specificity, PPV, and NPV were 97.10, 58.33, 93.06, and 77.78%, respectively. Choline-PET/CT has a high global sensitivity while WB-DW-MRI has a high specificity, and so they are complementary techniques. Future studies with more enrolled patients and a longer follow-up period will be required to confirm these data. The initial data show that the best technique for evaluating response after SBRT is choline-PET/CT. Trial registration number NCT02858128.

PURPOSE To evaluate the magnitude of systematic and random errors from a subset of 100 prostate and 26 head and neck (HN) cancer patients treated with conventional conformal radiotherapy and using image-guided radiotherapy (IGRT). After treatment, the uncertainties involved and the CTV to PTV margin were evaluated. MATERIAL AND METHODS An Elekta Synergy® linear accelerator was used, taking advantage of 3D on-board computed tomography. IGRT with no-action level (NAL) protocol was applied, reporting the 3D translation and rotation corrections. A statistical study was performed to analyse systematic, random and interobserver uncertainties, and, finally, to obtain the CTV to PTV margins. RESULTS The HN patients' uncertainties found were smaller than those of prostate patients. The CTV to PTV margins assessed, following the guidelines found in the literature, in the three dimensions of space (right-left, superior-inferior, anterior-posterior) were (5.3, 3.5, 3.2) mm for HN and (7.3, 7.0, 9.0) mm for prostate cancer treatments. CONCLUSIONS It was found that assessing all the involved uncertainties within radiation treatments was very revealing; their quality improves using IGRT techniques and performing extensive data analysis.

The oligometastatic status in the prostate is a new entity of metastatic patients in which their treatment allows to improve survival over standard treatments. There are several theories about their biological origin, one of them being alterations in the expression of miRNas This. was a retrospective multicentre study undertaken in patients with oligometastatic prostate cancer who were diagnosed and treated at one of 7 different Spanish healthcare centres. METHODS: The study included 22 patients; healthy and primary tumour biopsy tissue was analysed in 7+2 of them in order to determine if they had a characteristic microRNA expression profile. We quantified the expression of the following miRNAs: mir‑200a, mir‑200b, mir‑200c, mir‑210, mir‑95, mir‑96, mir‑654‑3p, mir‑543‑3p, mir‑21, mir‑16‑5p, mir‑191‑5p, and mir‑93‑5p, with the latter three being endogenous‑expression controls. RESULTS: Our results show that miRNA95, and to a lesser extent, miRNA654‑3p, were significantly underexpressed (or their expression was suppressed) in tumour tissue samples compared to normal perilesional tissue in all our patients; miRNA95 was underexpressed in 67% of the patients in our sample However, we detected no relationship between miRNA95 expression and the Gleason scores obtained for our patients. CONCLUSIONS: The simple size in our series are limited, but they do allow us to infer that there could be a specific miRNA expression signature in oligometastatic patients with prostate cancer, which may be of great interest in the development of future clinical trials and subsequent studies.

The main objective of image-guided radiation therapy (IGRT) equipment is to reduce and correct inherent errors in external radiotherapy processes. At the present time, there are different IGRT systems available, but here we will refer exclusively to the kilovoltage cone-beam CT onboard linear accelerator (CBkVCT) and the different aspects that, from a clinical point of view, should be taken into consideration before the implementation of this equipment.

We present a clinical case of a patient diagnosed with a retroperitoneal sarcoma, which received preoperative treatment with daily verification via computed tomography obtained with kilovoltage cone beam. We compare the benefit of this treatment compared to other conventional treatment without image guiding, reporting quantitative results.

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.

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.

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.

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.

CYP2D6 is a key enzyme in tamoxifen metabolism, transforming it into its main activemetabolite, 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). 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). 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 ¼ 0.013) and to 9.30 ng/ml (OR 3.99; p ¼ 0.007), respectively. These concentrations were comparable to those observed in EM patients receiving 20 mg of tamoxifen (p ¼ 0.13 and p ¼ 0.64, respectively). In CYP2D6 PM patients, increasing the standard tamoxifen dose two-fold or three-fold raisesendoxifen concentrations to levels similar to those of patients with EM phenotype. 2.381 JCR (2014) Q2, 21/79 Obstetrics & gynecology; Q3, 129/211 Oncology UEM

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.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.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).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.

Purpose: We present a literature review of risk analyses in radiotherapy to highlight the most reported risks and facilitate the spread of this valuable information so that professionals can be aware of these major threats before performing their own studies. Methods: We considered studies with at least an estimation of the probability of occurrence of an adverse event (O) and its associated severity (S). They cover external beam radiotherapy, brachytherapy, intraoperative radiotherapy, and stereotactic techniques. We selected only the works containing a detailed ranked series of elements or failure modes and focused on the first fully reported quartile as much. Afterward, we sorted the risk elements according to a regular radiotherapy procedure so that the resulting groups were cited in several works and be ranked in this way. Results: 29 references published between 2007 and February 2016 were studied. Publication trend has been generally rising. The most employed analysis has been the Failure mode and effect analysis (FMEA). Among references, we selected 20 works listing 258 ranked risk elements. They were sorted into 31 groups appearing at least in two different works. 11 groups appeared in at least 5 references and 5 groups did it in 7 or more papers. These last sets of risks where choosing another set of images or plan for planning or treating, errors related with contours, errors in patient positioning for treatment, human mistakes when programming treatments, and planning errors. Conclusion: There is a sufficient amount and variety of references for identifying which failure modes or elements should be addressed in a radiotherapy department before attempting a specific analysis. FMEA prevailed, but other studies such as “risk matrix” or “occurrence × severity” analyses can also lead professionals’ efforts. Risk associated with human actions ranks very high; therefore, they should be automated or at least peer-reviewed.

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. 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

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.

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.

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 semico nductor field effect tran sistors (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 tre atments. In vivo dosimetry was performed in 45 patients in cases involving primary tumors or relapses. The m ost 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 th e 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. This work was supported by grants IPT-300000-2010-3 and PI11/01659 from the Spanish Government and ERDF funds.

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.