Phase II Study of ENZAlutamide Combined With Hypofractionated Radiation Therapy (ENZART) for Localized Intermediate Risk Prostate Cancer.

Background: Intermediate-risk prostate cancer (PCa) is usually treated by a combination of external beam radiation therapy (EBRT) and a short course of androgen deprivation therapy (ADT). ADT is associated with multiple side effects, including weight gain, loss of libido, and hot flashes. In contrast, anti-androgen monotherapy is generally better tolerated in spite of higher rates of gynecomastia. Objective: This study assessed the effectiveness of enzalutamide monotherapy combined with hypofractionated EBRT (Hypo-EBRT) for treating intermediate risk prostate cancer. Method: This trial was a multicenter, open-label phase II study of 6 months of enzalutamide monotherapy combined with Hypo-EBRT for intermediate-risk prostate cancer. Hypo-EBRT was initiated 8-12 weeks after initiating enzalutamide. The primary endpoint was PSA decline >80% measured at the 25th week of enzalutamide administration. Secondary end-points included assessment of toxicity, changes in anthropomorphic body measurements, sexual hormones, and metabolic changes. Results: Sixty-two patients were included in the study from January 2018 to February 2020. A PSA decline of >80% was observed in all evaluable patients at the end of enzalutamide treatment and 92% achieved PSA values under 0.1 ngr/ml. All patients remain in PSA response (<80% reduction of the initial values) 6 months after the end of enzalutamide treatment. The most frequent adverse events were hypertension, asthenia, and gynecomastia. There were no significant changes in bone density, body mass index (BMI), or patient-reported outcomes (PROs). Conclusion: Enzalutamide monotherapy is very effective along with hEBRT in reducing PSA levels for patients with intermediate-risk prostate cancer. Longer follow-up is needed to confirm the potential use of this combination in future randomized trials.

Re-irradiation for high-grade gliomas: Has anything changed?

Optimal management after recurrence or progression of high-grade gliomas is still undefined and remains a challenge for neuro-oncology multidisciplinary teams. Improved radiation therapy techniques, new imaging methods, published experience, and a better radiobiological knowledge of brain tissue have positioned re-irradiation (re-RT) as an option for many of these patients. Decisions must be individualized, taking into account the pattern of relapse, previous treatment, and functional status, as well as the patient's preferences and expected quality of life. Many questions remain unanswered with respect to re-RT: Who is the most appropriate candidate, which dose and fractionation are most effective, how to define the target volume, which imaging technique is best for planning, and what is the optimal timing? This review will focus on describing the most relevant studies that include re-RT as salvage therapy, with the aim of simplifying decision-making and designing the best available therapeutic strategy.

Health-related quality of life in men with localized prostate cancer treated with radiotherapy: validation of an abbreviated version of the Expanded Prostate Cancer Index Composite for Clinical Practice in Spain.

BACKGROUND: Health-related quality of life (HRQoL) is greatly affected by prostate cancer (PCa) and associated treatments. This study aimed to measure the impact of radiotherapy on HRQoL and to further validate the Spanish version of the 16-item Expanded Prostate Cancer Index Composite (EPIC-16) in routine clinical practice. METHODS: An observational, non-interventional, multicenter study was conducted in Spain with localized PCa patients initiating treatment with external beam radiotherapy (EBRT) or brachytherapy (BQT). Changes from baseline in EPIC-16, University of California-Los Angeles Prostate Cancer Index (UCLA-PCI), and patient-perceived health status were longitudinally assessed at end of radiotherapy (V2) and 90 days thereafter (V3). Psychometric evaluations of the Spanish EPIC-16 were conducted. RESULTS: Of 516 patients enrolled, 495 were included in the analysis (EBRT, n = 361; BQT, n = 134). At baseline, mean (standard deviation [SD]) EPIC-16 global scores were 11.9 (7.5) and 10.3 (7.7) for EBRT and BQT patients, respectively; scores increased, i.e., HRQoL worsened, from baseline, by mean (SD) of 6.8 (7.6) at V2 and 2.4 (7.4) at V3 for EBRT and 4.2 (7.6) and 3.9 (8.2) for BQT patients. Changes in Spanish EPIC-16 domains correlated well with urinary, bowel, and sexual UCLA-PCI domains. EPIC-16 showed good internal consistency (Cronbach's alpha = .84), reliability, and construct validity. CONCLUSION: The Spanish EPIC-16 questionnaire demonstrated sensitivity, strong discriminative properties and reliability, and validity for use in clinical practice. EPIC-16 scores worsened after radiotherapy in different HRQoL domains; however, a strong tendency towards recovery was seen at the 3-month follow-up visit.

Oligometastases in prostate cancer: Ablative treatment.

Technological advances in radiotherapy have led to the introduction of techniques such as stereotactic body radiation therapy (SBRT), allowing the administration of ablative doses. The hypothesis that oligometastatic disease may be cured through local eradication therapies has led to the increasing use of SBRT in patients with this type of disease. At the same time, scientific advances are being made to allow the confirmation of clinically suspected oligometastatic status at molecular level. There is growing interest in identifying patients with oligometastatic prostate cancer (PCa) who may benefit from curative intent metastasis-directed therapy, including SBRT. The aim is to complement, replace or delay the introduction of hormone therapy or other systemic therapies. The present review aims to compile the evidence from the main ongoing studies and results on SBRT in relation to oligometastatic PCa; examine aspects where gaps in knowledge or a lack of consensus persist (e.g., optimum schemes, response assessment, identification and diagnosis of oligometastatic patients); and document the lack of first-level evidence supporting the use of such techniques.

Intimal sarcoma of the pulmonary artery with multiple lung metastases: Long-term survival case.

Pulmonary artery intimal sarcoma (PAIS) is a rare tumor with a very poor prognosis. Clinical and radiological findings usually mimic thromboembolic disease, leading to diagnostic delays. The treatment of choice is surgery, and adjuvant chemotherapy and radiotherapy have limited results. We report the case of a 48-year-old male patient, initially suspected with pulmonary thromboembolism. The angio-CT revealed a filling defect in the pulmonary artery trunk. The patient underwent surgery, resulting in with complete resection of the mass with a diagnosis of PAIS. The tumor progressed rapidly in the lung, requiring surgery of multiple lung metastases. The patient was treated with stereotactic body radiation therapy (SBRT) on two occasions for new pulmonary lesions. In the last followup (4 years after initial diagnosis), the patient was disease-free. In conclusion, SBRT proved to be an alternative treatment to metastasectomy, allowing palliative chemotherapy to be delayed or omitted, which may result in improved quality of life.

Assessment of the novel online delineation workshop dummy run approach using FALCON within a European multicentre trial in cervical cancer (RAIDs).

BACKGROUND AND PURPOSE: Online delineation workshops (ODW) permit training of geographically dispersed participants. The purpose is to evaluate the methodology of an ODW using FALCON to harmonize delineation within a European multicentre trial on locally advanced cervical cancer (LACC). MATERIAL AND METHODS: Two ODW included 46 clinicians (14 centres). Clinicians completed baseline (C1), guideline (C2) and final contours (C3) for external beam radiotherapy (EBRT) and brachytherapy (BT) for LACC. Interobserver and intraobserver variability was evaluated quantitatively (using the DICE index) and qualitatively compared to expert contours. RESULTS: Nine clinicians submitted for EBRT and BT for C1-C3. Thirty-two sent any contour. Interobserver quantitative comparisons for EBRT showed significant improvement for C2 vs. C1 for bowel, CTV node, CTV-p and GTV node with significant detriment for GTV node (C3 vs. C1; C2), CTV-p (C3 vs. C2) and bowel (C3 vs. C2), showing in general an improvement in C2 vs. C1, with a detriment in C3 vs. C2 for two target volumes and an organ at risk. For BT there was significant improvement for C2 vs. C1 for bladder, GTV, HR-CTV and IR-CTV, with significant detriment for bladder (C3 vs. C2), thus overall improvement in C2 vs. C1, with only a detriment in C3 vs. C2 for bladder. Centres using MRI imaging for BT contouring did significantly better in the BT case for HR-CTV than those which used other techniques (C2 vs. C1: p<0.005; C3 vs. C1: p=0.02). Intraobserver quantitative comparisons showed significant improvement contouring a region of interest between C2 vs. C1, C3 vs. C1 and C3 vs. C2 for EBRT and between C2 and C1 for BT. CONCLUSIONS: ODW offer training, initial contouring harmonization and allow assessment of centres.

Respuesta al tratamiento e intervalo de tiempo hasta la cirugía con radioterapia preoperatoria de curso corto en el cáncer de recto / Response to treatment and interval to surgery after preoperative short-course radiotherapy in rectal cancer

INTRODUCCIÓN: La radioterapia preoperatoria de curso corto con cirugía inmediata, mejora el control local del cáncer rectal. Las respuestas que consigue son de menor magnitud que las descritas con radioquimioterapia. Datos preliminares asocian esta menor respuesta al corto periodo hasta la cirugía. El objetivo de este estudio es analizar la respuesta obtenida con el esquema preoperatorio de curso corto y su correlación con el tiempo hasta la cirugía, analizando especialmente a los pacientes con fascia mesorrectal afectada. MÉTODOS: Se analiza retrospectivamente a 155 pacientes tratados con radioterapia preoperatoria (5×5Gy). Se cuantificó la respuesta tumoral en términos de tasas de respuesta completa patológica, reducción del estadio, grado de regresión tumoral y estado del margen de resección circunferencial. RESULTADOS: El intervalo medio radioterapia-cirugía fue de 23 días. Se alcanzaron respuestas completas patológicas en el 2,2% y reducción del estadio en el 28%. No se detectaron diferencias entre estas tasas y el intervalo hasta la cirugía. Ochenta y ocho pacientes tenían resonancia de estadificación (31 con fascia mesorrectal comprometida). La media de tiempo hasta la intervención en pacientes con fascia comprometida y cirugía R0 fue de 27 días y si R1 de 16 días (p = 0,016). El punto de corte de 20 días alcanzó la mayor probabilidad de lograr un margen circunferencial negativo entre los pacientes con fascia mesorrectal comprometida, aunque sin alcanzar significación estadística: RR 3,036, IC del 95%=0,691-13,328, p = 0,06. CONCLUSIONES: Tras la radioterapia preoperatoria de curso corto, un intervalo > 20 días potencia la probabilidad de lograr un margen de resección libre en pacientes con fascia mesorrectal comprometida

INTRODUCTION: Preoperative short-course radiotherapy with immediate surgery improves local control in patients with rectal cancer. Tumor responses are smaller than those described with radiochemotherapy. Preliminary data associate this lower response to the short period until surgery. The aim of this study is to analyze the response to preoperative short-course radiotherapy and its correlation with the interval to surgery especially analyzing patients with mesorectal fascia involvement. METHODS: A total of 155 patients with locally advanced rectal cancer treated with preoperative radiotherapy (5×5Gy) were retrospectively analyzed. Tumor response in terms of rates of complete pathological response, downstaging, tumor regression grading and status of the circumferential resection margin were quantified. RESULTS: The mean interval from radiotherapy to surgery was 23 days. The rate of complete pathological response was 2.2% and 28% experienced downstaging (stage decreased). No differences between these rates and interval to surgery were detected. Eighty-eight patients had magnetic resonance imaging for staging (in 31 patients the mesorectal fascia was involved).The mean time to surgery in patients with involvement of the fascia and R0 surgery was 27 days and 16 days if R1 (P = .016). The cutoff of 20 days reached the highest probability of achieving a free circumferential resection margin between patients with mesorectal fascia involvement, with no statistically significant differences: RR 3.036 95% CI = (0.691-13.328),P = .06. CONCLUSIONS: After preoperative short-course radiotherapy, an interval>20 days enhances the likelihood of achieving a free circumferential resection margin in patients with mesorectal fascia involvement

Response to treatment and interval to surgery after preoperative short-course radiotherapy in rectal cancer. / Respuesta al tratamiento e intervalo de tiempo hasta la cirugía con radioterapia preoperatoria de curso corto en el cáncer de recto.

INTRODUCTION: Preoperative short-course radiotherapy with immediate surgery improves local control in patients with rectal cancer. Tumor responses are smaller than those described with radiochemotherapy. Preliminary data associate this lower response to the short period until surgery. The aim of this study is to analyze the response to preoperative short-course radiotherapy and its correlation with the interval to surgery especially analyzing patients with mesorectal fascia involvement. METHODS: A total of 155 patients with locally advanced rectal cancer treated with preoperative radiotherapy (5×5Gy) were retrospectively analyzed. Tumor response in terms of rates of complete pathological response, downstaging, tumor regression grading and status of the circumferential resection margin were quantified. RESULTS: The mean interval from radiotherapy to surgery was 23 days. The rate of complete pathological response was 2.2% and 28% experienced downstaging (stage decreased). No differences between these rates and interval to surgery were detected. Eighty-eight patients had magnetic resonance imaging for staging (in 31 patients the mesorectal fascia was involved).The mean time to surgery in patients with involvement of the fascia and R0 surgery was 27 days and 16 days if R1 (P=.016). The cutoff of 20 days reached the highest probability of achieving a free circumferential resection margin between patients with mesorectal fascia involvement, with no statistically significant differences: RR 3.036 95% CI=(0.691-13.328), P=.06. CONCLUSIONS: After preoperative short-course radiotherapy, an interval>20 days enhances the likelihood of achieving a free circumferential resection margin in patients with mesorectal fascia involvement.

Oligometastatic disease, the curative challenge in radiation oncology.

The concept of oligometastatic disease was first described by Hellman and Weichselbaum in 1995. The mere insight of this concept led to the hypothesis that this disease may be cured using local ablative weapons. Surgery has already demonstrated this hypothesis. Surgery limitations, either technical or due to refusal or associated comorbidity, have led to implement alternative ablative options such as stereotactic body radiation therapy (SBRT). SBRT evolved from (stereotactic radiosurgery) because of the need to irradiate extracranial lesions and has been shown to be safe and effective. SBRT achieves local control rates ranging from 70%-90%, but highly variable survival rates depending on the group analyzed. Series with heterogeneous metastatic sites and tumor origin have reported 20% survival rates at 2-3 years, similar to those achieved with surgery. Despite its excellent results, SBRT still faces significant clinical challenges. Its optimal integration with systemic treatment is unknown, and response assessment is very difficult. However, the greatest challenge lies in selection of patients most likely to remain oligometastatic, those who will most benefit from the technique. Biomarkers, molecular signatures, that accurately predict the biological behavior of malignancy are needed. The expression profile of specific miRNAs has been shown to have a potential in this regard.

Rosette-forming glioneuronal tumour (RGNT) of the fourth ventricle: a highly aggressive case.

BACKGROUND: The rosette-forming glioneuronal tumour (RGNT) is a rarely encountered tumour that has been included as a new entity in the 2007 edition of the "World Health Organization (WHO) Classification of Tumours of the Central Nervous System". We describe a rather unusual case of multifocal cerebellar RGNT, located in the spinal cord and displaying leptomeningeal spread. CLINICAL PRESENTATION: Twenty-four-year-old male with history of long-lasting headaches. A magnetic resonance scan revealed three heterogeneous lesions located within both cerebellar hemispheres and the left cerebellopontine angle, in addition to a spinal cord lesion at the level of the cervical region, and images of leptomeningeal spread. Interventions were performed in two stages; these involved resection of two cerebellar lesions, with a histopathological diagnosis of RGNT with atypical microvascular proliferation and focal necrosis. Although these tumours appear to be benign, our case debuted in an aggressive form, both from the radiological point of view and with respect to its histopathological characteristics. For this reason, the patient received adjuvant therapy with chemotherapy and radiotherapy. CONCLUSIONS: Experience of RGNT is limited. The prognostic significance of the histological findings of vascular proliferation and necrosis is still unknown. The clinical improvement in our patient endorses our decision to perform aggressive treatment.

Characterization and adequacy of the use of radiotherapy and its trend in time.

BACKGROUND AND PURPOSE: Characterization of radiotherapy activity and its trend over time. Gathering of parameters for future planning of our resources, applicable to similar population areas. Performing a clinical audit of appropriate use of radiotherapy. MATERIAL AND METHODS: Analysis of 9782 patients treated between 1998 and 2008. Descriptive statistics of pathologies and social/demographic characteristics. Intention of treatment. The rate of radiotherapy utilization was estimated and compared with those considered optimal. Rate of reirradiation. RESULTS: The average global rate of radiotherapy utilization for the period was 32.7%. It increased by 23% between 1998 and 2008, while the population of the area rose by 1.04%, equaling an average 1.13 irradiations/1000 inhabitants/year. Radiation treatment has increased by 13.6, 2.3, 1.6 and 1.06 times in patients with prostate, breast, rectal and lung cancer, respectively. Eight percent of radiotherapy treatments involve concurrent chemotherapy. The proportion of treatments with palliative intent was 18.2%. The overall underutilization of radiation therapy in our environment was an estimated 13.4%. CONCLUSIONS: The grade of adequacy of radiation rates in relation with scientific evidence was globally considered suboptimal, especially in lung cancer. There was an upward trend of irradiation in breast and prostate cancer, tending toward rates considered optimal.

Radiotherapy in rectal cancer: development, adequacy and radiotherapy utilisation rate. A comparative analysis with the most frequent tumour sites.

INTRODUCTION: Radiotherapy is a basic weapon in the local treatment of multiple solid tumors. The radiotherapy activity has been evaluated in our centre during the past eleven years. The study focused on rectal cancer. MATERIALS AND METHODS: This is a descriptive study of all radiotherapy procedures performed between January 1998 and December 2008. It quantifies the workload of each pathology treated, the rate of irradiation and its adequacy with optimal rates of irradiation according to the best available scientific evidence. RESULTS: We quantified 9,622 external radiotherapy procedures of which 6,009 were associated with the five pathologies that involved the highest workloads. Of these, 905 were performed in rectal cancer. The workloads due to cancers of the breast, prostate, lung, gynaecological pathologies and rectal cancers were 23.2%, 11.8%, 11.6%, 6.3% and 9.3% respectively. The real "radiotherapy utilisation rates" of these pathologies were 62%, 20.2%, 34.3%, 21% and 64% respectively, while the "rates of adequacy" were 74.7%, 33.6%, 45.1%, 60% and 104.8%. CONCLUSIONS: The "radiotherapy utilisation rate" for rectal cancer was equivalent to the estimated optimum rate as defined on the basis of reference groups. The therapy utilised developed chronologically in parallel with the available scientific evidence. The radiotherapy utilisation rates for breast and prostate cancer gradually increased, with a tendency to reach optimal rates. Radiotherapy as a treatment for lung cancer was underutilised. In global terms, the rate of utilisation of radiation therapy was low, although it displayed a tendency to increase.

Radiation oncology: future needs and equipment. Current situation in Spain.

Spain's radiation oncology infrastructure has evolved in terms of both quantity and structure since the last analysis was carried out in 1999. The purpose of this paper is to describe the current facilities, basically consisting of external radiotherapeutic units, and to present a calculation model for estimating the number of irradiation units required to guarantee equitable cover for radiotherapeutic treatment. An electronic questionnaire was designed to be accessed via a link on the Spanish Association of Radiotherapy and Oncology Web page. The questionnaire provides details of the current state of Spain's radiotherapeutic facilities, and a descriptive study has been performed with analytical data. The scope of the study included all the centres providing oncology-radiotherapy in Spain. The units analysed encompassed the centres and irradiation units actively providing care in 2004. Ninety-seven centres were detected, in which 177 external radiotherapy units were registered. Forty-five of these were cobalt units and 132 were accelerators. The rate of radiotherapy use in Spain based on the best scientific evidence available and on its rate of use with cancer has been estimated at 61%. The number of external irradiation units available in 2004 (177) is clearly lower than the number desirable (266-316).