Enhancing Androgen Deprivation Therapy (ADT) integration in prostate cancer: Insights for Stereotactic Body Radiotherapy (SBRT) and brachytherapy modalities.

The utilization of Androgen Deprivation Therapy (ADT) in conjunction with Stereotactic Body Radiotherapy (SBRT) and Brachytherapy (BT) boost in prostate cancer treatment is a subject of ongoing debate and evolving clinical practice. While contemporary trends lean towards underutilizing ADT with these modalities, existing evidence suggests that its omission may lead to potentially inferior oncologic outcomes. Recommendations for ADT use should be patient-centric, considering individual risk profiles and comorbidities, with a focus on achieving optimal oncologic outcomes while minimizing potential side effects. Ongoing clinical trials, such as PACE-C, SPA, SHIP 0804, and SHIP 36B, are anticipated to provide valuable insights into the optimal use and duration of ADT in both SBRT and BT settings. Until new evidence emerges, it is recommended to initiate ADT for unfavorable intermediate-risk and high-risk prostate cancer patients undergoing radiotherapy, with a minimum duration of 6 months for unfavorable intermediate-risk patients and at least 12 months for those with high-risk characteristics. The decision to incorporate ADT into these radiation therapy modalities should be individualized, acknowledging the unique needs of each patient and emphasizing a tailored approach to achieve the best possible oncologic outcomes.

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.

SEOM clinical guidelines for diagnosis and treatment of glioblastoma (2017).

Glioblastoma (GB) is the most common brain malignancy and accounts for over 50% of all high-grade gliomas. Radiotherapy (RT) with concomitant and adjuvant temozolomide (TMZ) chemotherapy is the current standard of care for patients with newly diagnosed GB up to age 70. Recently, a new standard of care has been adopted for elderly patients (≥ 65 years) based on short course of RT and TMZ. Several clinically relevant molecular markers that assist in diagnosis and prognosis have recently been identified. The treatment for recurrent GB is not well defined, and decision-making is usually based on prior strategies as well as several clinical and radiological factors. The presence of neurologic deficits and seizures can significantly impact quality of life.

Intermittent versus continuous androgen deprivation therapy to biochemical recurrence after external beam radiotherapy: a phase 3 GICOR study.

PURPOSE: We compared biochemical control and quality of life with intermittent (6 months) versus continuous (36 months) androgen deprivation therapy (ADT) in a non-inferiority randomized phase 3 trial in patients with biochemical failure (BF) after external beam radical radiotherapy (EBRT). MATERIALS AND METHODS: Patients were stratified according to the Gleason score (GS) and were classified as low risk with a GS < 6 and 7 (3 + 4) and high risk with a GS of 7 (4 + 3) and >7. Patients were followed with PSA determinations and quality-of-life assessments (QLQ C-30 and QLQ PR-25) every 6 months for a period of 3 years. BF after radiation was defined as a PSA level of nadir +2 ng/ml. Disease progression (DP) after ADT was defined as PSA ≥4 ng/ml (BF) and/or metastases. RESULTS: Seventy-seven patients were included in this multicenter phase 3 trial from 2005 to 2009. Thirty-eight and 39 patients were included in the intermittent and continuous groups, respectively. The median follow-up for both groups was 48 months (40-68). DP after ADT in the intermittent group was seen in three patients (distant metastases in one patient) versus 0 in the continuous group. The QLQ-C30 and QLQ PR-25 scores did not show any statistically difference between the two ADT groups. CONCLUSIONS: No significant differences were seen in DP and QLQ between intermittent (6 months) and continuous (36 months) ADT in patients with BF after EBRT.

Management of prostate cancer patients following radiation therapy after radical surgery referred from urology to radiation oncology departments in Spain.

PURPOSE: To define usual clinical management of prostate cancer (PCa) patients following postoperative radiation therapy (RT) (adjuvant or salvage) and its evolution over time in radiation oncology (RO) departments in Spain. METHODS: An epidemiological, cross-sectional, multicentre study was conducted. 567 PCa patients that had undergone radical prostatectomy (RP) and received postoperative RT between February and December of both 2006 and 2011 participated in the study. In patients from 2006, health-related quality of life (HRQoL) was assessed using the EPIC questionnaire. Investigators completed a specific survey on two clinical cases of adjuvant and salvage RT. RESULTS: 70.6 % of patients received salvage RT versus 29.4 % who received adjuvant RT; no significant differences were found in terms of frequency for each procedure between both the years. Regarding the survey, a positive surgical margin was the main criteria used in adjuvant RT decision making. In terms of salvage RT scenario, 85.7 % of the investigators stated that adjuvant RT should have been offered instead, 81.4 % of the investigators agreed on a PSA score >0.2 ng/mL as the main criteria for identifying biochemical recurrence after RP, and 67.4 % of investigators did not consider any PSA score for ruling out salvage RT treatment. CONCLUSIONS: Most patients are referred to RO departments to receive salvage RT. Despite the publication of three IA evidence level randomized clinical trials, the patterns for using adjuvant and salvage RT did not change from 2006 to 2011, although patients' profile did. A consensus regarding postoperative RT indications should be reached in order to correct this controversial situation.

Hormonal changes after localized prostate cancer treatment. Comparison between external beam radiation therapy and radical prostatectomy. / Cambios hormonales después del tratamiento de cáncer de próstata localizado. Comparación entre radioterapia de haz externo y prostatectomía radical.

OBJECTIVE: To determine the influence of radical prostatectomy (RP) and external beam radiation therapy (EBRT) on the hypothalamic pituitary axis of 120 men with clinically localized prostate cancer treated with RP or EBRT exclusively. MATERIALS AND METHODS: 120 patients with localized prostate cancer were enrolled. Ninety two patients underwent RP and 28 patients EBRT exclusively. We measured serum levels of luteinizing hormone, follicle stimulating hormone (FSH), total testosterone (T), free testosterone, and estradiol at baseline and at 3 and 12 months after treatment completion. RESULTS: Patients undergoing RP were younger and presented a higher prostate volume (64.3 vs. 71.1 years, p<0.0001 and 55.1 vs. 36.5 g, p<0.0001; respectively). No differences regarding serum hormonal levels were found at baseline. Luteinizing hormone and FSH levels were significantly higher in those patients treated with EBRT at three months (luteinizing hormone 8,54 vs. 4,76 U/l, FSH 22,96 vs. 8,18 U/l, p<0,0001) while T and free testosterone levels were significantly lower (T 360,3 vs. 414,83ng/dl, p 0,039; free testosterone 5,94 vs. 7,5pg/ml, p 0,018). At 12 months FSH levels remained significantly higher in patients treated with EBRT compared to patients treated with RP (21,01 vs. 8,51 U/l, p<0,001) while T levels remained significantly lower (339,89 vs. 402,39ng/dl, p 0,03). CONCLUSIONS: Prostate cancer treatment influences the hypothalamic pituitary axis. This influence seems to be more important when patients with prostate cancer are treated with EBRT rather than RP. More studies are needed to elucidate the role that prostate may play as an endocrine organ.

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.

31Phosphorus magnetic resonance spectroscopy in the assessment of head and neck tumors.

PURPOSE: 31Phosphorus magnetic resonance spectroscopy (31P-MRS) provides biochemical information in a noninvasive way. The aim of this work was: (a) to characterize the 31P spectrum of advanced head and neck tumors, and (b) to evaluate the spectral changes after treatment and to correlate them with the pathologic response. METHODS AND MATERIALS: A total of 20 patients diagnosed with advanced head and neck tumors and 7 healthy controls participated in the study. The tumor mass and its contralateral side were studied by means of 31P-MRS before and after treatment. Neck muscles of a control group were also studied. RESULTS: Tumors presented ratios of phosphomonoesters (PME), phosphodiesters (PDE), and inorganic phosphate (Pi) with respect to the adenosine triphosphate (ATP), significantly higher and a PCr (phosphocreatine)/ATP ratio lower than the neck muscle of volunteers or the contralateral side. The PDE/ATP and PME/ATP ratio values obtained before therapy were similar, independent of the later response to treatment. However, when there was a complete response, the ratios measured after treatment were decreased. CONCLUSION: These results show the existence of significant differences between the 31phosphorus spectrum of tumors and neck muscle, but also between the tumors and their contralateral sides. Moreover, 31P-MRS is able to detect metabolic changes after a complete response. These results suggest that 31P-MRS would be useful in the evaluation of the clinical response of head and neck tumors.

Preoperative simultaneous chemoradiotherapy in locally advanced cancer of the oral cavity and oropharynx.

Combined chemoradiotherapy (CT/RT) treatments appear to yield better results for advanced tumours of the head and neck than do conventional therapies. In the present study, CT/RT was used preoperatively in unresectable tumors of the oral cavity and oropharynx. Forty patients were entered prospectively into a phase II study. Treatment consisted of three cycles of chemotherapy with cisplatin and 5-day infusion of fluorouracil (FU), and the addition of simultaneous radiotherapy (30 Gy) from the second to third cycles. Patients with resectable residual disease or complete clinical response underwent surgery. All patients later received a second phase of irradiation (30 Gy) and two cycles of chemotherapy only in responders. During the first phase of treatment, 22 (55%) patients presented mucositis grades III-IV. Mean weight loss was 7%. Twelve patients were admitted for parenteral nutrition. Thirty-six (90%) patients obtained clinical response, which was complete in 15 (37%). Thirty-two of the 40 underwent surgery. The percentage of pathologic complete responses (PCR) was 35% (14 patients). With a median follow-up of 21 months, the median survival of patients was 23 months, and 19 (47%) of them are disease-free. A high PCR rate was attained with this treatment regimen. Toxicity was significant, but tolerable with adequate support measures.

Time-related changes in functional activity of mouse spermatozoa during in vitro or in vivo incubation.

The kinetics of functional modifications during in vivo or in vitro incubation was studied in spermatozoa from Albino Swiss mice, obtained from cauda epididymis (E) or from uterus (U) or oviduct (O) post copulation (p.c.). Results clearly suggest that functional activity as reflected by measurements of motility, hypoosmotic swelling test and acrosome reaction differs according to the segments of the reproductive tract from which they were collected. The comparison of results obtained after equivalent periods of in vitro or in vivo incubation, shows that the time course of changes in sperm motility and percentage of swollen sperm is similar in both conditions. Since the percentage of acrosome-reacted gametes was higher in O, at all times scored, oviductal environment appeared to be capable of inducing this phenomenon. Our experimental conditions seemed to be adequate for completion of spermatozoa maturation and successful interaction between male and female gametes as reflected by the results of fertilization rate and embryo cleavage.

Do patients with metastatic urothelial carcinoma benefit from docetaxel as second-line chemotherapy?

PURPOSE: To evaluate the efficacy and toxicity of docetaxel regimen as second-line after failure of a platinum-based chemotherapy. METHODS: Between May 2005 and June 2008, we retrospectively analyzed the data of 22 patients who had evidence of disease progression after one prior platinum-based regimen for metastatic urothelial carcinoma. Patients were treated with two different docetaxel dose schedules: (1) docetaxel 60 mg/m(2) every 21 days for unfit patients or (2) docetaxel 75 mg/m(2) every 21 days for fit patients. RESULTS: Median number of docetaxel cycles was three. Overall disease control rate was 18 %. Of the 22 patients, no patient achieved complete or partial response and four patients had stable disease. Median progression-free survival was 1.67 months and median overall survival was 3.12 months. Neutropenia was the most common adverse event. CONCLUSIONS: This study identifies that docetaxel as second-line chemotherapy has low activity and was associated with significant toxicity.

Infrastructures, treatment modalities, and workload of radiation oncology departments in Spain with special attention to prostate cancer.

AIM: The purpose of the study was to describe infrastructures, treatment modalities, and workload in radiation oncology (RO) in Spain, referred particularly to prostate cancer (PC). METHODS: An epidemiologic, cross-sectional study was performed during 2008-2009. A study-specific questionnaire was sent to the 108 RO-registered departments. RESULTS: One hundred and two departments answered the survey, and six were contacted by telephone. Centers operated 236 treatment units: 23 (9.7 %) cobalt machines, 37 (15.7 %) mono-energetic linear accelerators, and 176 (74.6 %) multi-energy linear accelerators. Sixty-one (56.4 %) and 33 (30.5 %) departments, respectively, reported intensity-modulated radiation therapy (IMRT) and image-guided RT (IGRT) capabilities; three-dimensional-conformal RT was used in 75.8 % of patients. Virtual simulators were present in 95 departments (88.0 %), 35 use conventional simulators. Fifty-one departments (47.2 %) have brachytherapy units, 38 (35.2 %) perform prostatic implants. Departments saw a mean of 24.9 new patients/week; the number of patients treated annually was 102,054, corresponding to 88.4 % of patients with a RT indication. In 56.5 % of the hospitals, multidisciplinary teams were available to treat PC. CONCLUSIONS: Results provide an accurate picture of current situation of RO in Spain, showing a trend toward the progressive introduction of new technologies (IMRT, IGRT, brachytherapy).

SEOM clinical guidelines for diagnosis and treatment of glioblastoma (2017)

Glioblastoma (GB) is the most common brain malignancy and accounts for over 50% of all high-grade gliomas. Radiotherapy (RT) with concomitant and adjuvant temozolomide (TMZ) chemotherapy is the current standard of care for patients with newly diagnosed GB up to age 70. Recently, a new standard of care has been adopted for elderly patients (≥ 65 years) based on short course of RT and TMZ. Several clinically relevant molecular markers that assist in diagnosis and prognosis have recently been identified. The treatment for recurrent GB is not well defined, and decision-making is usually based on prior strategies as well as several clinical and radiological factors. The presence of neurologic deficits and seizures can significantly impact quality of life (AU9

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Nueva lista de Medicamentos esenciales de la Organización / New list of essential medicines of the Organization World Health Day (20th list March 2017)

La tecnología avanzada aplicada a las ciencias de la salud se traduce en mayor probabilidad de diagnóstico ytratamiento precoces, lo que permite en muchas ocasiones un incremento de la esperanza de vida, sin embargo,esto también acarrea dilemas éticos entre la de nición adecuada de calidad de vida, hasta cuando mantener aun paciente con soporte arti cial, entre otras.El estado de gravedad extrema en el que se encuentran los enfermos críticos los hace una población de graninterés para investigación y experimentación, sin embargo, el estado de sedación profunda al que estánsometidos, los trastornos agudos de la conciencia (delirio), encefalopatías de varias etiologías, entre otros, loshacen no competentes para decidir sobre su participación o no en proyectos de investigación, debiendo serconsiderados como un grupo vulnerable cuyo enrolamiento en trabajos científicos debe ser analizado por uncomité de bioética.En el presente trabajo refexionamos y tratamos de dar sustento científico, en base a datos históricos ycontemporáneos, sobre ésta delicada temática(AU)

¿Por qué diclofenaco fue removido de la lista de medicamentos esenciales de la Organización Mundial de la Salud? / Why was diclofenac removed from the list of essential drugs of the World Health Organization?

(AU) Diclofenaco presenta un mayor riesgo cardiovascular respecto a otros AINE tradicionales, siendo similar al observado en los COX-2 selectivos, esto es, cercano al riesgo aterotrombótico de etoricoxib, superior a celeco- xib y a otros AINE tradicionales como ibuprofeno o naproxeno. En el año 2013 la Organización Mundial de la Salud, excluyó de su 18ava lista de medicamentos esenciales a diclofenaco, basándose principalmente en la in- formación de seguridad. Frente a otras alternativas como ibuprofeno, diclofenaco no presenta ninguna ventaja en términos de seguridad gastrointestinal y tiene una desventaja clara sobre riesgo cardiovascular.

(AU) Diclofenac has a higher cardiovascular risk than other traditional NSAIDs, it is similar to that observed in COX-2 selective, it is near to atherothrombotic risk of etoricoxib, celecoxib and superior to other traditional NSAIDs like ibuprofen or naproxen. In 2013 the World Health Organization removed from the 18ava list of essential drugs this medicament, this decision was based primarily on information about security of diclon- fenac. Compared to other alternatives such as ibuprofen diclofenac have not advantage in terms of gastroin- testinal safety and has a distinct disadvantage on cardiovascular risk.

Mordedura de serpiente, una enfermedad en el olvido / Snakebite, a disease into oblivion

El accidente ofídico es una de las enfermedades consideradas por la Organización Mundial de la Salud como negligenciadas; a pesar de ser una condición altamente evitable, cada cinco minutos muere en el mundo una persona por mordedura de serpiente. La incidencia de accidente ofídico en Ecuador se ha incrementado en la última década, afecta principalmente a personas que habitan en zonas rurales con escaso acceso a servicios de salud y en condiciones de alta vulnerabilidad social. La administración oportuna de antídotos específicos pueden salvar la vida de las personas afectadas; no obstante, actualmente el mundo enfrenta una escasez crítica de suero antiofídico; la industria farmacéutica abandonó la producción hace décadas, quienes quedan aún en el mercado, no abastecen la necesidad actual, la escasa oferta de anti veneno específico, el costo elevado, las regulaciones asfixiantes, entre otros, se han convertido en limitantes del acceso. Las regulaciones sanitarias exigibles a la industria farmacéutica tienen por fin último el garantizar la calidad de sus productos; no obstante, algunas veces, estas buenas intenciones de exigencias de calidad y fortalecimiento institucional se convierten en una barrera de acceso a medicamentos esenciales. Ecuador y Colombia cayeron en las tres últimas décadas de ser países autosustentables en la producción de suero antiofídico para cubrir las necesidades de salud de su población, a ser dependientes de las importaciones de anti veneno de centro y Norteamérica. Tras haber podido convertirse en productores para abastecimiento regional, cerraron sus plantas de producción. ¿Será acaso, que los esfuerzos por alcanzar estándares internacionales de calidad sin un plan de inversión de recursos técnicos y financieros que le permita competitividad a la institucionalidad pública puede considerarse un “autogol”? (AU)

Snake Bites is considered by WHO as negligence diseases; despite being a highly preventable condition, every five minutes someone dies in the world by snakebite. The incidence of snakebites in Ecuador has increased in the last decade, mainly affecting people living in rural areas with little access to health services and social vulnerability.Timely just administration of specific antidotes can save the lives of those affected; however, today the world is facing a critical shortage of antivenom; the pharmaceutical industry stopped producting for decades, who remain today, not supplying the current need, the limited supply of specific antivenom, high cost, hard regulations, among others, are limiting access.The health regulations to the pharmaceutical industry have finally order to guarantee the quality of their products; however, sometimes good intentions about quality standards and development the institutional capacity, are becoming a barrier to access to essential drugs.Ecuador and Colombia fell in the last three decades of being self-supporting countries in producing anti venom to meet the health needs of its population, to be dependent on imported antivenom from Central and North America. Having been able to become producers for regional supply, they closed its production. Could it be, that efforts to achieve international quality standards without an investment plan of technical and financial resources to generate competitive public institutions can be considered as “own goal”?Create laws to ensure access to these drugs as safe and effective is the “fundamental reason” of the health authority; the citizens expect a dual flow; on the one hand the effort to ensure the regulation, and simultaneously, smart investment in public institutions to producing these biological products (antivenom), in order to this public institutions is strengthened and not disapear, as were the cases of Ecuador and Colombia

Bilateral testicular germ cell tumours: a single hospital experience.

BACKGROUND: The incidence of testicular germ cell tumours (TGCT) is increasing and the improvement in survival may lead to an increased incidence of bilateral tumours. We examined the incidence, prognosis, clinical and histological characteristics, treatment and outcome of patients with bilateral TGCTs based on 15 years of experience from a single institution. MATERIAL AND METHODS: We reviewed the charts from all patients treated for a testicular tumour germ cell at Hospital Vall d'Hebron in Barcelona, Spain. The information was retrospectively obtained from the patients' hospital. All the patients were evaluated with clinical history, physical exam, serum markers (alphaFP, LDH and betahCG), ultrasonographic evaluation of the testicles, computed tomography (CT) scans of the chest, abdomen and pelvis, surgery, location and histology of first and second tumour, treatment after the surgery and follow-up. RESULTS: Of 151 patients with TGCT, 8 (5.3%) developed bilateral tumours, seven (4.6%) were metachronous and one (0.7%) synchronous tumours. Two patients underwent testis-sparing surgery for the second tumour. All the patients are alive without evidence of disease based on physical exam, tumour markers and CT scan. CONCLUSIONS: Survival in patients with bilateral testicular germ cell tumours (BTGCT) is similar to that of patients with unilateral TGCT. There is no standard therapy to treat BTGCT and each patient requires a tailored therapeutic treatment.