Random laser emission from whole blood as the active medium.

We introduce a proof of concept for multimode random laser (RL) emission with fresh whole blood (WB) as the active medium. The experimental principle is adapted from RL emission using rhodamine 6G (R6G). We achieved conditions for fresh WB to fluoresce with stochastic amplification of stimulated emission of radiation. The random conditions are placed with SiO2 particles, suspended in isotonic solvent. The results we report are for: (1) R6G-RL, with 2 nm bandwidth centered at 567 nm, and (2) RL emission for WB at 969 nm and 437 nm, of sub-3 nm bandwidth. For validation purposes, we show that the pumping energy threshold for RL emission from blood is consistent with R6G-RL.

Análisis de supervivencia de los pacientes con cáncer de próstata con factores patológicos desfavorables tratados con prostatectomía radical y radioterapia de rescate tras la recidiva y persistencia bioquímica / Survival analysis of patients with prostate cancer and unfavorable risk factors treated with radical prostatectomy and salvage radiotherapy after biochemical recurrence and persistence

OBJETIVO: Analizar la supervivencia de los pacientes con cáncer de próstata (CP) con factores pronósticos desfavorables (FPD) tratados con PR y radioterapia de rescate (RTR) tras recidiva bioquímica (RB) y persistencia bioquímica (PB). MATERIAL Y MÉTODO: Análisis retrospectivo de 446 pacientes con al menos uno de los siguientes FPD: score de Gleason ≥ 8, estadio patológico ≥ pT3 y/o márgenes quirúrgicos positivos (MQ+). El criterio de RB fue la elevación del PSA por encima de 0,4 ng/ml. Evaluación de supervivencia mediante Kaplan-Meier y log-rank. Para identificar factores de riesgo con posible influencia en la respuesta a RTR y la supervivencia causa-específica (SCE) se usó análisis uni y multivariable (regresión de Cox). RESULTADOS: Mediana de seguimiento: 72 (rango 37-122) meses, mediana de tiempo hasta RB: 42 (rango 20-112) meses. El 36,3% presentaron RB. Presentaron respuesta bioquímica a la RTR 121 (74,7%) pacientes. La supervivencia libre de recaída (SLR) después de la RTR a los 3, 5, 8 y 10 años fue del 95,7, del 92,3, del 87,9 y del 85%, la SG a los 5, 10 y 15 años fue del 95,6, del 86,5 y del 73,5%. La SCE a los 5, 10 y 15 años fue del 99,1, del 98,1 y del 96,6%, respectivamente. Solo el tiempo hasta la RB < 24 meses (HR = 2,55, p = 0,01) se comportó como un factor predictor independiente de SLR después de RTR. CONCLUSIONES: La PR solo consigue control de la enfermedad a los 10años en aproximadamente la mitad de los casos. El tratamiento multimodal secuencial (PR + RTR cuando precise) aumenta este control bioquímico hasta > 87%, lográndose una larga SCE. Los pacientes con un tiempo hasta recidiva > 24 meses respondieron mejor al tratamiento de rescate

OBJECTIVE: Survival analysis of patients with prostate cancer (PCa) with adverse prognostic factors (APF) treated with radical prostatectomy (RP) and salvage radiotherapy (SRT) after biochemical recurrence (BR) or biochemical persistence (BP). MATERIALS AND METHODS: Retrospective analysis of 446 patients with at least one of the following APF: Gleason score ≥ 8, pathologic stage ≥ pT3 and/or positive surgical margins. BR criteria used was PSA level over 0.4 ng/ml. A survival analysis using Kaplan-Meier was performed to compare the different variable categories with log-rank test. In order to identify risk factors for SRT response and cancer specific survival (CSS) we performed univariate and multivariate analyses using Cox regression. RESULTS: Mean follow up: 72 (IQR 27-122) months, mean time to BR: 42 (IQR 20-112) months, mean PSA level at BR: 0.56 (IQR 0.42-0.96). BR was present in 36.3% of the patients. Biochemical response to SRT was observed in 121 (75.7%) patients. Recurrence-free survival (RFS) rates after SRT at 3, 5, 8 and 10 years were 95.7%, 92.3%, 87.9%, and 85%; overall survival (OS) rates after 5, 10 and 15 years was 95.6%, 86.5% and 73.5%, respectively. CSS rates at 5, 10 and 15 years were 99.1%, 98.1% and 96.6%. Only time to BR < 24 months (HR = 2.55, P = .01) was identified as an independent risk factor for RFS after SRT. CONCLUSIONS: In these patients, RP only controls the disease in approximately half of the cases. Multimodal sequential treatment (RP+SRT when needed) increases this control, achieving high CSS rates and biochemical control in over 87% of the patients. Patients with time to recurrence > 24 months responded better to rescue treatment

Survival analysis of patients with prostate cancer and unfavorable risk factors treated with radical prostatectomy and salvage radiotherapy after biochemical recurrence and persistence. / Análisis de supervivencia de los pacientes con cáncer de próstata con factores patológicos desfavorables tratados con prostatectomía radical y radioterapia de rescate tras la recidiva y persistencia bioquímica.

OBJECTIVE: Survival analysis of patients with prostate cancer (PCa) with adverse prognostic factors (APF) treated with radical prostatectomy (RP) and salvage radiotherapy (SRT) after biochemical recurrence (BR) or biochemical persistence (BP). MATERIALS AND METHODS: Retrospective analysis of 446 patients with at least one of the following APF: Gleason score ≥8, pathologic stage ≥pT3 and/or positive surgical margins. BR criteria used was PSA level over 0.4ng/ml. A survival analysis using Kaplan-Meier was performed to compare the different variable categories with log-rank test. In order to identify risk factors for SRT response and cancer specific survival (CSS) we performed univariate and multivariate analyses using Cox regression. RESULTS: Mean follow up: 72 (IQR 27-122) months, mean time to BR: 42 (IQR 20-112) months, mean PSA level at BR: 0.56 (IQR 0.42-0.96). BR was present in 36.3% of the patients. Biochemical response to SRT was observed in 121 (75.7%) patients. Recurrence-free survival (RFS) rates after SRT at 3, 5, 8 and 10years were 95.7%, 92.3%, 87.9%, and 85%; overall survival (OS) rates after 5, 10 and 15years was 95.6%, 86.5% and 73.5%, respectively. CSS rates at 5, 10 and 15years were 99.1%, 98.1% and 96.6%. Only time to BR <24months (HR=2.55, P=.01) was identified as an independent risk factor for RFS after SRT. CONCLUSIONS: In these patients, RP only controls the disease in approximately half of the cases. Multimodal sequential treatment (RP+SRT when needed) increases this control, achieving high CSS rates and biochemical control in over 87% of the patients. Patients with time to recurrence >24months responded better to rescue treatment.

Improving the quality of care in the molecular era for children and adolescents with medulloblastoma.

PURPOSE: Elevated mortality and morbidity rates persist in pediatric patients with medulloblastoma. We present a clinical audit of a real-world cohort of patients in search for pragmatic measures to improve their management and outcome. METHODS/PATIENTS: All pediatric patients with medulloblastoma treated between 2003 and 2016 at a Spanish reference center were reviewed. In the absence of internationally accepted quality indicators (QIs) for pediatric CNS tumors, diagnostic, therapeutic, survival, and time QIs were defined and assessed. RESULTS: Fifty-eight patients were included, 24% were younger children (< 3 years), 36% high risk (anaplastic, metastasis, or surgical residue > 1.5 cm2), and 40% standard risk. Five-year OS was 59.2% (95% CI 47-75); 5-year PFS 36.4% (95% CI 25-53). Five main areas of quality assurance were identified: diagnosis, global strategy, frontline treatment modalities, outcomes, and long-term and end-of-life care. A set of 34 QIs was developed and applied. Lack of central pathology review, delay in the incorporation of novel molecular markers, and absence of a neurocognitive and quality-of-life evaluation program were some of the audit findings. CONCLUSIONS: This real-world research study resulted in the development of a pragmatic set of QIs, aimed to improve clinical audits and quality of care given to children and adolescents with medulloblastoma. We hope that our findings will serve as a reference to further develop a quality assurance system with specific QIs for pediatric CNS tumors in the future and that this will ultimately improve the survival and quality of life of these patients.

Survival after biochemical failure in prostate cancer treated with radiotherapy: Spanish Registry of Prostate Cancer (RECAP) database outcomes.

INTRODUCTION: The clinical course in patients with prostate cancer (PCa) after biochemical failure (BF) has received limited attention. This study analyzes survival time from recurrence, patterns of progression, and the efficacy of salvage therapies in patients treated with radical or postoperative radiotherapy (RT). METHODS: This is a multicenter retrospective comparative study of 1135 patients diagnosed with BF and treated with either radical (882) or postoperative (253) RT. Data correspond to the RECAP database. Clinical, tumor, and therapeutic characteristics were collected. Descriptive statistics, survival estimates, and comparisons of survival rates were calculated. RESULTS: Time to BF from initial treatment (RT or surgery) was higher in irradiated patients (51 vs 37 months). At a median follow-up of 102 months (14-254), the 8-year cause-specific survival (CSS) was 80.5%, without significant differences between the radical (80.1%) and postoperative (83.4%) RT groups. The 8-year metastasis-free survival rate was 57%. 173 patients (15%) died of PCa and 29 (2.5%) of a second cancer. No salvage therapy was given in 15% of pts. Only 5.5% of pts who underwent radical RT had local salvage treatment and 71% received androgen deprivation (AD) ± chemotherapy. The worst outcomes were in patients who developed metastases after BF (302 pts; 26.5%) and in cases with a Gleason > 7. CONCLUSIONS: In PCa treated with radiotherapy, median survival after BF is relatively long. In this sample, no differences in survival rates at 8-years have been found, regardless of the time of radiotherapy administered. AD was the most common treatment after BF. Metastases and high Gleason score are adverse variables. To our knowledge, this is the first study to compare outcomes after BF among patients treated with primary RT vs. those treated with postoperative RT and to evaluate recurrence patterns, treatments administered, and causes of death. The results allow avoiding overtreatment, improving quality of life, without negatively affecting survival.

Consensus on management of castration-resistant prostate cancer on behalf of the Urological Tumours Working Group (URONCOR) of the Spanish Society of Radiation Oncology.

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.

Consensus statement on definition, diagnosis, and management of high-risk prostate cancer patients on behalf of the Spanish Groups of Uro-Oncology Societies URONCOR, GUO, and SOGUG

Purpose. Prostate cancer (PCa) is the most prevalent malignancy in men and the second cause of mortality in industrialized countries. Methods. Based on Spanish Register of PCa, the incidence of high-risk PCa is 29%, approximately. In spite of the evidence-based beneficial effect of radiotherapy and androgen deprivation therapy in high-risk PCa, these patients (pts) are still a therapeutic challenge for all specialists involved, in part due to the absence of comparative studies to establish which of the present disposable treatments offer better results. Results. Nowadays, high-risk PCa definition is not well consensual through the published oncology guides. Clinical stage, tumour grade, and number of risk factors are relevant to be considered on PCa prognosis. However, these factors are susceptible to change depending on when surgical or radiation therapy is considered to be the treatment of choice. Other factors, such as reference pathologist, different diagnosis biopsy schedules, surgical or radiotherapy techniques, adjuvant treatments, biochemical failures, and follow-up, make it difficult to compare the results between different therapeutic options. Conclusions. This article reviews important issues concerning high-risk PCa. URONCOR, GUO, and SOGUG on behalf of the Spanish Groups of Uro-Oncology Societies have reached a consensus addressing a practical recommendation on definition, diagnosis, and management of high-risk PCa (AU)

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Adjuvant versus salvage radiotherapy in prostate cancer: multi-institutional retrospective analysis of the Spanish RECAP database

Purpose. To compare adjuvant radiotherapy (ART) to salvage radiotherapy (SRT) after radical prostatectomy (RP) in a cohort of prostate cancer (PCa) patients. The primary aim was to comparatively assess 2- and 5-year biochemical relapse-free survival (BRFS). A secondary aim was to identify predictors of survival. Patients and methods. Data were acquired from the RECAP database, a population-based prostate cancer registry in Spain. Inclusion criteria included RP (with or without lymphadenectomy) followed by ART or SRT. A total of 702 patients were analyzed. Pre-RT PSA values (>0.5 vs. ≤0.5 ng/ml), pathological stage (T1-2 vs. T3-4), post-surgical Gleason score (≤7 vs. 8-10), margin status (positive vs. negative), hormonal treatment (yes vs. no), and RT dose (≤66 Gy vs. >66 Gy) were evaluated to assess their impact on BRFS. Results. The mean patient age in the ART and SRT groups, respectively, was 64 years (range 42-82) and 64.8 years (range 42-82). Median follow-up after RT in the whole sample was 34 months (range 3-141). A total of 702 patients were included: 223 (31.8%) received ART and 479 (68.2%) SRT. BRFS rates (95% CI) in the ART and SRT groups at months 24 and 60 were, respectively: 98.1% (95.9-100.0%) vs. 91.2% (88.2-94.2%) and 84.5% (76.4-92.6%) vs. 74.0% (67.4-80.7%) (p = 0.004). No significant differences in OS were observed (p = 0.053). The following variables were significant predictors of biochemical recurrence in the SRT group: (1) positive surgical margin status (p = 0.049); (2) no hormonotherapy (p = 0.03); (3) total prostate dose ≤66 Gy (p = 0.004); and pre-RT PSA ≥0.5 ng/ml (p = 0.013). Conclusions. This is the first nationwide study in Spain to evaluate a large cohort of PCa patients treated with RP followed by postoperative RT. ART yielded better 2- and 5-year BRFS rates, although OS was equivalent. These findings are consistent with most other published studies and support ART in patients with adverse prognostic characteristics after radical prostatectomy. Prospective trials are needed to compare immediate ART to early SRT to better determine their relative benefits (AU)

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Consensus statement on definition, diagnosis, and management of high-risk prostate cancer patients on behalf of the Spanish Groups of Uro-Oncology Societies URONCOR, GUO, and SOGUG.

PURPOSE: Prostate cancer (PCa) is the most prevalent malignancy in men and the second cause of mortality in industrialized countries. METHODS: Based on Spanish Register of PCa, the incidence of high-risk PCa is 29%, approximately. In spite of the evidence-based beneficial effect of radiotherapy and androgen deprivation therapy in high-risk PCa, these patients (pts) are still a therapeutic challenge for all specialists involved, in part due to the absence of comparative studies to establish which of the present disposable treatments offer better results. RESULTS: Nowadays, high-risk PCa definition is not well consensual through the published oncology guides. Clinical stage, tumour grade, and number of risk factors are relevant to be considered on PCa prognosis. However, these factors are susceptible to change depending on when surgical or radiation therapy is considered to be the treatment of choice. Other factors, such as reference pathologist, different diagnosis biopsy schedules, surgical or radiotherapy techniques, adjuvant treatments, biochemical failures, and follow-up, make it difficult to compare the results between different therapeutic options. CONCLUSIONS: This article reviews important issues concerning high-risk PCa. URONCOR, GUO, and SOGUG on behalf of the Spanish Groups of Uro-Oncology Societies have reached a consensus addressing a practical recommendation on definition, diagnosis, and management of high-risk PCa.

Adjuvant versus salvage radiotherapy in prostate cancer: multi-institutional retrospective analysis of the Spanish RECAP database.

PURPOSE: To compare adjuvant radiotherapy (ART) to salvage radiotherapy (SRT) after radical prostatectomy (RP) in a cohort of prostate cancer (PCa) patients. The primary aim was to comparatively assess 2- and 5-year biochemical relapse-free survival (BRFS). A secondary aim was to identify predictors of survival. PATIENTS AND METHODS: Data were acquired from the RECAP database, a population-based prostate cancer registry in Spain. Inclusion criteria included RP (with or without lymphadenectomy) followed by ART or SRT. A total of 702 patients were analyzed. Pre-RT PSA values (>0.5 vs. ≤0.5 ng/ml), pathological stage (T1-2 vs. T3-4), post-surgical Gleason score (≤7 vs. 8-10), margin status (positive vs. negative), hormonal treatment (yes vs. no), and RT dose (≤66 Gy vs. >66 Gy) were evaluated to assess their impact on BRFS. RESULTS: The mean patient age in the ART and SRT groups, respectively, was 64 years (range 42-82) and 64.8 years (range 42-82). Median follow-up after RT in the whole sample was 34 months (range 3-141). A total of 702 patients were included: 223 (31.8%) received ART and 479 (68.2%) SRT. BRFS rates (95% CI) in the ART and SRT groups at months 24 and 60 were, respectively: 98.1% (95.9-100.0%) vs. 91.2% (88.2-94.2%) and 84.5% (76.4-92.6%) vs. 74.0% (67.4-80.7%) (p = 0.004). No significant differences in OS were observed (p = 0.053). The following variables were significant predictors of biochemical recurrence in the SRT group: (1) positive surgical margin status (p = 0.049); (2) no hormonotherapy (p = 0.03); (3) total prostate dose ≤66 Gy (p = 0.004); and pre-RT PSA ≥0.5 ng/ml (p = 0.013). CONCLUSIONS: This is the first nationwide study in Spain to evaluate a large cohort of PCa patients treated with RP followed by postoperative RT. ART yielded better 2- and 5-year BRFS rates, although OS was equivalent. These findings are consistent with most other published studies and support ART in patients with adverse prognostic characteristics after radical prostatectomy. Prospective trials are needed to compare immediate ART to early SRT to better determine their relative benefits.

Factores predictivos de toxicidad urinaria y rectal tras radioterapia externa conformada en el cáncer de próstata: correlación de parámetros clínicos, tumorales y dosimétricos con radioterapia radical y postoperatoria / Predictors of urinary and rectal toxicity after external conformed radiation therapy in prostate cancer: Correlation between clinical, tumour and dosimetric parameters and radical and postoperative radiation therapy

Objetivo: Determinar la toxicidad rectal y urinaria tras radioterapia externa (EBRT), valorando resultados de pacientes sometidos a tratamiento radical o postoperatorio por cáncer de próstata y su correlación con potenciales factores de riesgo. Método: Trescientos treinta y tres pacientes tratados con EBRT, 285 radicales y 48 tras cirugía (39 rescate; 9 adyuvante). Se recopilaron variables clínicas, tumorales y dosimétricas a correlacionar con parámetros de toxicidad. Se elaboraron árboles de decisión según el grado de significación estadística. Resultados: La toxicidad aguda severa, tanto urinaria como rectal, fue del 5,4% y del 1,5%, respectivamente. La toxicidad crónica fue del 4,5% y del 2,7%. Veintisiete pacientes presentaron hematuria y 9 rectitis hemorrágica. Veinticinco (7,5%) presentaron secuelas permanentes limitantes. Los pacientes con síntomas del tracto urinario inferior previos a la RT presentaron peor tolerancia, con mayor toxicidad vesical aguda (p = 0,041). Respecto a la toxicidad rectal aguda, pacientes con dosis media en recto > 45 Gy, con tratamiento anticoagulante/antiagregante, desarrollaban un 63% de toxicidad leve frente al 37% de los pacientes con dosis media rectal< 45 Gy y sin anticoagulantes. No se han podido establecer factores predictivos de toxicidad crónica en el análisis multivariable. Las secuelas a largo plazo son más elevadas en los pacientes con cirugías urológicas previas a la RT que siguen tratamiento anticoagulante. Conclusiones: La tolerancia a EBRT es buena y la toxicidad severa poco frecuente. La sintomatología urinaria basal es el factor predictor que más influye en la toxicidad urinaria aguda. La toxicidad rectal se relaciona con la dosis media al recto y con el tratamiento anticoagulante/antiagregante. No existen diferencias significativas en la toxicidad grave entre RT radical y a RT postoperatoria

Objective: To determine rectal and urinary toxicity after external beam radiation therapy (EBRT), assessing the results of patients who undergo radical or postoperative therapy for prostate cancer (pancreatic cancer) and their correlation with potential risk factors. Method: A total of 333 patients were treated with EBRT. Of these, 285 underwent radical therapy and 48 underwent postoperative therapy (39 cases of rescue and 9 of adjuvant therapy). We collected clinical, tumour and dosimetric variable to correlate with toxicity parameters. We developed decision trees based on the degree of statistical significance. Results: The rate of severe acute toxicity, both urinary and rectal, was 5.4% and 1.5%, respectively. The rate of chronic toxicity was 4.5% and 2.7%, respectively. Twenty-seven patients presented haematuria, and 9 presented haemorrhagic rectitis. Twenty-five patients (7.5%) presented permanent limiting sequela. The patients with lower urinary tract symptoms prior to the radiation therapy presented poorer tolerance, with greater acute bladder toxicity (P = 0.041). In terms of acute rectal toxicity, 63% of the patients with mean rectal doses > 45Gy and anticoagulant/antiplatelet therapy developed mild toxicity compared with 37% of the patients with mean rectal doses <45 Gy and without anticoagulant therapy. We were unable to establish predictors of chronic toxicity in the multivariate analysis. The long-term sequelae were greater in the patients who underwent urological operations prior to the radiation therapy and who were undergoing anticoagulant therapy. Conclusions: The tolerance to EBRT was good, and severe toxicity was uncommon. Baseline urinary symptoms constitute the predictor that most influenced the acute urinary toxicity. Rectal toxicity is related to the mean rectal dose and with anticoagulant/antiplatelet therapy. There were no significant differences in severe toxicity between radical versus postoperative radiation therapy

Predictors of urinary and rectal toxicity after external conformed radiation therapy in prostate cancer: Correlation between clinical, tumour and dosimetric parameters and radical and postoperative radiation therapy. / Factores predictivos de toxicidad urinaria y rectal tras radioterapia externa conformada en el cáncer de próstata: correlación de parámetros clínicos, tumorales y dosimétricos con radioterapia radical y postoperatoria.

OBJECTIVE: To determine rectal and urinary toxicity after external beam radiation therapy (EBRT), assessing the results of patients who undergo radical or postoperative therapy for prostate cancer (pancreatic cancer) and their correlation with potential risk factors. METHOD: A total of 333 patients were treated with EBRT. Of these, 285 underwent radical therapy and 48 underwent postoperative therapy (39 cases of rescue and 9 of adjuvant therapy). We collected clinical, tumour and dosimetric variable to correlate with toxicity parameters. We developed decision trees based on the degree of statistical significance. RESULTS: The rate of severe acute toxicity, both urinary and rectal, was 5.4% and 1.5%, respectively. The rate of chronic toxicity was 4.5% and 2.7%, respectively. Twenty-seven patients presented haematuria, and 9 presented haemorrhagic rectitis. Twenty-five patients (7.5%) presented permanent limiting sequela. The patients with lower urinary tract symptoms prior to the radiation therapy presented poorer tolerance, with greater acute bladder toxicity (P=0.041). In terms of acute rectal toxicity, 63% of the patients with mean rectal doses >45Gy and anticoagulant/antiplatelet therapy developed mild toxicity compared with 37% of the patients with mean rectal doses <45 Gy and without anticoagulant therapy. We were unable to establish predictors of chronic toxicity in the multivariate analysis. The long-term sequelae were greater in the patients who underwent urological operations prior to the radiation therapy and who were undergoing anticoagulant therapy. CONCLUSIONS: The tolerance to EBRT was good, and severe toxicity was uncommon. Baseline urinary symptoms constitute the predictor that most influenced the acute urinary toxicity. Rectal toxicity is related to the mean rectal dose and with anticoagulant/antiplatelet therapy. There were no significant differences in severe toxicity between radical versus postoperative radiation therapy.

The number of risk factors is the strongest predictor of prostate cancer mortality: multi-institutional outcomes of an extreme-risk prostate cancer cohort.

PURPOSE: To report treatment outcomes in a cohort of extreme-risk prostate cancer patients and identify a subgroup of patients with worse prognosis. MATERIALS AND METHODS: Extreme-risk prostate cancer patients were defined as patients with at least one extreme-risk factor: stage cT3b-cT4, Gleason score 9-10 or PSA > 50 ng/ml; or patients with 2 or more high-risk factors: stage cT2c-cT3a, Gleason 8 and PSA > 20 ng/ml. Overall survival (OS), cause-specific survival (CSS), clinical-free survival (CFS), and biochemical non-evidence of disease (bNED) survival are the four outcomes of interest in a population of 1341 patients. RESULTS: With a median follow-up of 71.5 months, 5- and 10-year bNED survival, CFS, CSS and OS for the entire cohort were 77.1 % and 57.0, 89.2 and 78.9 %, 97.4 and 93.6 %, and 92.0 and 71.3 %, respectively. On multivariate analysis, PSA and clinical stage were associated with bNED survival. PSA and Gleason score predicted for CFS, whereas only Gleason score predicted for OS. When a simplified model was performed using the "number of risk factors" variable, this model provided the best distinction between patients with ≥2 extreme-risk factors and patients with 2 high-risk factors, showing a hazard ratio (HR) of 1.737 (p = 0.0003) for bNED survival, HR 1.743 (p = 0.0448) for OS and an HR of 3.963 (p = 0.0039) for the CSS endpoint. CONCLUSIONS: Patients presenting at diagnosis with two extreme-risk criteria have almost fourfold higher risk for prostate cancer mortality. Such patients should be considered for more aggressive multimodal treatments.

Frequency analysis for an extended photoacoustic transport model.

In photoacoustic imaging, the signal attenuation is a well-known source of artifacts over the image reconstruction. It is recognized that this is caused by optical absorption effects and by the ultrasound broadband scattering. However, the sound dispersion is generally neglected, although it appears notably in thick or heterogeneous tissues. In the present Letter, we give an experimental example in which both attenuation and sound dispersion are dealt with as relevant features to be taken into consideration. An analytic perspective of these perturbations leads us to a waveform transport-model extension that provides a linear description of the induced acoustic effects. We find a near match between the theoretical predictions and the experimental results in the frequency domain. These outcomes approximate projection data that represent forward solutions in photoacoustic image reconstruction.

Androgen deprivation and radiotherapy in patients with prostate cancer and cardiovascular risk factors: clinical controversies

Introduction. Recent reports of an association between androgen deprivation treatment (ADT) and increased risk of cardiovascular (CV) events have generated debate on the use of ADT in patients with prostate cancer (PCa) and CV comorbidities. This study aims to describe the recommendations of radiation oncologists in the most controversial aspects of treating such patients. Materials and methods. The project involved 61 oncologists and comprised 4 phases: (1) selection of the most controversial aspects in the administration of ADT in patients with a history of CV disease and PCa, (2) selection of the most relevant published evidence, (3) preparation of case reports, (4) critical reading and discussion. Therapeutic procedures were classified as “highly recommendable”, “recommendable in some cases”, or “not recommendable/not applicable”. For each item assessed, the mode of the scores given, and the percentage of experts who selected each score were calculated. Results. The panel recommended that patients with high/very high-risk PCa and a history of CV disease should receive gonadotropin-releasing hormone agonists (GnRHa). ADT with GnRHa for 24–36 months + radiotherapy (RT) was also considered highly recommendable. In intermediate-risk PCa and a history of CV, ADT with GnRHa for 6–8 months + RT, and not administering ADT were considered highly recommendable. Conclusions. Studies are necessary to investigate the impact of ADT on CV mortality in patients who benefit most from adjuvant ADT in terms of survival. In the meantime, the experts believe that clinical evidence on the proven therapeutic benefits of ADT should override concerns about potential cardiac toxicity (AU)

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Androgen deprivation and radiotherapy in patients with prostate cancer and cardiovascular risk factors: clinical controversies.

INTRODUCTION: Recent reports of an association between androgen deprivation treatment (ADT) and increased risk of cardiovascular (CV) events have generated debate on the use of ADT in patients with prostate cancer (PCa) and CV comorbidities. This study aims to describe the recommendations of radiation oncologists in the most controversial aspects of treating such patients. MATERIALS AND METHODS: The project involved 61 oncologists and comprised 4 phases: (1) selection of the most controversial aspects in the administration of ADT in patients with a history of CV disease and PCa, (2) selection of the most relevant published evidence, (3) preparation of case reports, (4) critical reading and discussion. Therapeutic procedures were classified as "highly recommendable", "recommendable in some cases", or "not recommendable/not applicable". For each item assessed, the mode of the scores given, and the percentage of experts who selected each score were calculated. RESULTS: The panel recommended that patients with high/very high-risk PCa and a history of CV disease should receive gonadotropin-releasing hormone agonists (GnRHa). ADT with GnRHa for 24-36 months + radiotherapy (RT) was also considered highly recommendable. In intermediate-risk PCa and a history of CV, ADT with GnRHa for 6-8 months + RT, and not administering ADT were considered highly recommendable. CONCLUSIONS: Studies are necessary to investigate the impact of ADT on CV mortality in patients who benefit most from adjuvant ADT in terms of survival. In the meantime, the experts believe that clinical evidence on the proven therapeutic benefits of ADT should override concerns about potential cardiac toxicity.

Angular distribution of random laser emission.

We present an experimental analysis of the angular distribution of the emission of a random laser (RL) operating in the diffusive regime (∼1% volume fraction of scatterers). The RL ensemble was made of silica particles suspended in a 1:1 methanol:water matrix with Rhodamine 6G dye as the active medium. We found that, for specific pumping-energy-dependent scattering strength, the RL spectrum reached stable features that were angularly preserved. From the analysis, we propose that this defines a novel parametric condition that may well be the equivalent of the RL critical volume, as proposed by Letokhov.

Intraoperative radiotherapy for the treatment of resectable locally advanced gastric adenocarcinoma: topography of locoregional recurrences and long-term outcomes

INTRODUCTION: To report feasibility, tolerance, anatomical sites of upper abdominal locoregional recurrence and long-term outcome of gastric cancer patients treated with surgery and a component of intraoperative electron beam radiotherapy (IORT). MATERIALS AND METHODS: From January 1995 to December 2010, 32 patients with primary gastric adenocarcinoma treated with curative resection (R0) [total gastrectomy (n = 9; 28 %), subtotal (n = 23; 72 %) and D2 lymphadenectomy in all patients] and apparent disease confined to locoregional area [Stage: II (n = 15; 47 %), III (n = 17; 53 %)] were treated with a component of IORT (IORT applicator size 5-9 cm in diameter, dose 10-15 Gy, beam energy 6-5 MeV) over the celiac axis and peripancreatic nodal areas. Sixteen (50 %) patients also received adjuvant treatment (external beam radiotherapy n = 6, chemoradiation n = 9, chemotherapy alone n = 1). RESULTS: With a median follow-up time of 40 months (range, 2-60), locoregional recurrence was observed in five (16 %) patients (4 nodal in hepatic hilum and 1 anastomotic). Only pN1 patients developed locoregional relapse. No recurrence was observed in the IORT-treated target volume (celiac trunk and peripancreatic nodes). Overall survival at 5 years was 54.6 % (95 % CI: 48.57-60.58). Postoperative mortality was 6 % (n = 2) and postoperative complications 19 % (n = 6). CONCLUSIONS: It is feasible to integrate IORT as a component of radiotherapy in combined modality therapy of gastric cancer. Local control is high in the radiation boosted area, but marginal regional extension (in particular, involving the hepatic hilum) might be considered as part of the anatomic IORT target volume at risk in pN+ patients (AU)