Radiation toxicity grading after chemoradiotherapy of canine urinary tract carcinomas: Comparing VRTOG to VRTOG_v2.0.

Radiation toxicities may be underestimated after treatment of transitional cell carcinoma in dogs' lower urinary tract. Assessing acute and late toxicities and differentiating them from progressive disease (PD) impacts further therapeutic approach. We retrospectively assessed dogs treated with definitive-intent chemoradiotherapy (12 × 3.8 Gy, various first-line chemotherapeutics). Local tumour control, radiation toxicities and survival were evaluated. We classified radiation toxicities according to the previously published radiation toxicity scheme "VRTOG" as well as the updated version, "VRTOG_v2.0". Fourteen dogs with transitional cell carcinoma of bladder ± urethra (n = 8), +prostate (n = 3) or solely urethra (n = 3), were included. Median follow-up was 298 days (range 185-1798 days), median overall survival 305 days (95%CI = 209;402) and 28.6% deaths were tumour-progression-related. Acute radiation toxicity was mild and self-limiting with both classification systems: In VRTOG, 5 dogs showed grade 1, and 1 dog grade 2 toxicity. In VRTOG_v2.0, 2 dogs showed grade 1, 3 dogs grade 2, and 3 dogs grade 3 toxicity. Late toxicity was noted in 14.2% of dogs (2/14) with the VRTOG, both with grade 3 toxicity. With VRTOG_v2.0, a larger proportion of 42.9% of dogs (6/14) showed late toxicities: Four dogs grade 3 (persistent incontinence), 2 dogs grade 5 (urethral obstructions without PD resulting in euthanasia). At time of death, 5 dogs underwent further workup and only 3 were confirmed to have PD. With the updated VRTOG_v2.0 classification system, more dogs with probable late toxicity are registered, but it is ultimately difficult to distinguish these from disease progression as restaging remains to be the most robust determinant.

Carbon-ion radiotherapy for urological cancers.

Carbon-ions are charged particles with a high linear energy transfer, and therefore, they make a better dose distribution with greater biological effects on the tumors compared with photons and protons. Since prostate cancer, renal cell carcinoma, and retroperitoneal sarcomas such as liposarcoma and leiomyosarcoma are known to be radioresistant tumors, carbon-ion radiotherapy, which provides the advantageous radiobiological properties such as an increasing relative biological effectiveness toward the Bragg peak, a reduced oxygen enhancement ratio, and a reduced dependence on fractionation and cell-cycle stage, has been tested for these urological tumors at the National Institute for Radiological Sciences since 1994. To promote carbon-ion radiotherapy as a standard cancer therapy, the Japan Carbon-ion Radiation Oncology Study Group was established in 2015 to create a registry of all treated patients and conduct multi-institutional prospective studies in cooperation with all the Japanese institutes. Based on accumulating evidence of the efficacy and feasibility of carbon-ion therapy for prostate cancer and retroperitoneal sarcoma, it is now covered by the Japanese health insurance system. On the other hand, carbon-ion radiotherapy for renal cell cancer is not still covered by the insurance system, although the two previous studies showed the efficacy. In this review, we introduce the characteristics, clinical outcomes, and perspectives of carbon-ion radiotherapy and our efforts to disseminate the use of this new technology worldwide.

Boron neutron capture therapy for urological cancers.

Boron neutron capture therapy is based on a nuclear reaction between the nonradioactive isotope boron-10 and either low-energy thermal neutrons or high-energy epithermal neutrons, which generate high linear energy transfer α particles and a recoiled lithium nucleus (7 Li) that selectively destroys the DNA helix in tumor cells. Boron neutron capture therapy is an emerging procedure aimed at improving the therapeutic ratio for the traditional treatment of various malignancies, which has been studied clinically in a variety of diseases, including glioblastoma, head and neck cancer, cutaneous melanoma, hepatocellular carcinoma, lung cancer, and extramammary Paget's disease. However, boron neutron capture therapy has not been clinically performed for urological cancers, excluding genital extramammary Paget's disease that appeared at the scrotum to penis area. In this review, we aimed to provide an updated summary of the current clinical literature of patients treated with boron neutron capture therapy and to focus on the future prospects of boron neutron capture therapy for urological cancers.

Magnetic Resonance Imaging-guided Adaptive Radiotherapy for Urological Cancers: What Urologists Should Know.

Magnetic resonance imaging (MRI)-guided radiotherapy allows for online adaptation of the radiation plan on the basis of anatomical and functional changes during treatment. MRI-guided radiotherapy holds significant promise for broadening the therapeutic window for multiple urological cancers.

Prevention of radiotherapy induced enteropathy by probiotics (PREP): protocol for a double-blind randomized placebo-controlled trial.

BACKGROUND: Radiation induced enteropathy is a common complication of radiotherapy for pelvic tumors and adversely affects patient quality of life. Probiotics are thought to restore bowel microflora to optimal levels and reinforce intestinal barrier capacity. Although probiotics are effective in the treatment of radiation induced enteropathy, less is known about their efficacy to prevent radiation induced enteropathy. METHODS: This double-blind randomized placebo-controlled study will investigate the efficacy of probiotics to prevent radiation-induced enteropathy in patients with gynecologic or urologic cancer who received pelvic radiotherapy. The study is designed to enroll 248 eligible patients, who will be randomized 1:1 to a probiotic or placebo group. Toxicities will be evaluated using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. DISCUSSION: The primary aim of this study is to provide high level evidence for the ability of probiotics to prevent acute radiation induced enteropathy. The secondary aims are to determine the effects of probiotics on the incidence of chronic radiation induced enteropathy and the safety of probiotics in patients with gynecologic or urologic cancer. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT03978949 , Registered on 7 June 2019).

A 25-year perspective on the evolution of radiation treatment of urologic cancers.

Advances in radiotherapy technology and technique over the last 3 decades have revolutionized radiation treatment options for genitourinary malignancies. The development of more focused and accurate radiation treatment has facilitated safe delivery of dose-escalated treatment that improves disease control and the development of shorter-duration hypofractionated treatment regimens that are more convenient for patients and improve access to treatment. The management of oligometastatic disease is evolving with ablative treatment of oligometastasis and the primary for select patients and shorter-duration palliative treatment regimens. Work is ongoing to personalize radiation treatment regimens for genitourinary malignancies based on molecular biomarkers.

[Clinical trials that have changed our practices 2010-2020]. / Les essais cliniques en radiothérapie qui ont changé les pratiques 2010­2020.

PURPOSE: This article aims to describe and list the clinical trials that have changed our practices in breast cancer, urological cancer, gynecological cancer, cancer of the upper aerodigestive tract and digestive cancer in the last ten years. MATERIAL AND METHODS: We listed and selected the studies published between 2010 and 2020. The articles were identified on the basis of a Medline search with PubMed and knowledge of the authors. RESULTS: Five to six trials were selected in breast cancer, urological cancers, gynecological cancers, cancers of the upper aerodigestive tract and digestive cancers asking the different fundamental questions in radiotherapy. CONCLUSION: Depending on the pathologies, the questions raised over the past 10 years remain fundamental questions such as the place of neoadjuvant treatment, the place of hypofractionation or the type of chemotherapy concomitant with radiotherapy.

Perioperative therapies for urological cancers.

Although surgery with curative intent is critical for management of many localized cancers, multimodal therapy including neoadjuvant and adjuvant therapy has been introduced to increase the effectiveness of local control of surgery and prolong survival. However, strong evidence supporting the utility of such multimodal therapy is limited. The utility of perioperative chemotherapy has been extensively investigated in bladder cancer, and several randomized controlled trials have indicated the benefit of neoadjuvant cisplatin-based chemotherapy in muscle-invasive bladder cancer. Regrettably, perioperative therapy for other urological cancers is controversial; therefore, no definitive conclusions have been drawn. Recently, the number of trials has rapidly increased due to the development of immune checkpoint inhibitors, used alone or in combination with other modalities. In this review, we summarize the current status and supporting evidence for perioperative therapies such as neoadjuvant and adjuvant therapies for urological cancers, including prostate cancer, urothelial cancer and renal cell carcinoma.

Prognostic impact of local radiotherapy on metastatic urothelial carcinoma patients receiving systemic chemotherapy.

OBJECTIVE: To clarify the prognostic impact of local radiotherapy on metastatic urothelial carcinoma patients treated by systemic chemotherapy. METHODS: Of the 228 metastatic urothelial carcinoma patients treated with systemic chemotherapy, 97 received radiotherapy mainly to metastatic sites. In patients for whom the purpose of radiotherapy was not specified, more than 50 Gy irradiation was considered to be for disease consolidation for survival analysis, while less than 50 Gy was categorized as palliation. According to the Kaplan-Meier method, we analysed overall survival from the initiation of treatment for metastatic urothelial carcinoma until death or the last follow-up, using the log-rank test to assess the significance of differences. The Cox model was applied for prognostic factor analysis. RESULTS: Overall, there was no significant difference in survival between patients with and those without radiotherapy (P = 0.1532). When analysing the patients undergoing consolidative radiotherapy separately, these 25 patients showed significantly longer survival than the 72 patients with palliative radiotherapy (P = 0.0047), with a 3-year overall survival of 43.3%. Of the present cohort, 22 underwent metastasectomy for disease consolidation, and there was no overlapping case between the metastasectomy cohort and cohort receiving consolidative radiotherapy. After controlling for four independent prognostic factors (sex, performance status, haemoglobin level and number of organs with metastasis) in our previous study, radiotherapy for disease consolidation showed a marginal value (hazard ratio = 0.666, P = 0.0966), while metastasectomy remained significant (hazard ratio = 0.358, P = 0.0006). CONCLUSIONS: In the selected patients, long-term disease control could be achieved after consolidative radiotherapy for metastatic urothelial carcinoma disease. Our observations suggest that local ablative therapy (surgery or radiotherapy) could facilitate long-term disease control. However, the treatment decision should be individualized because of the lack of randomized control trials.

The role of adjuvant radiotherapy after surgery for upper and lower urinary tract urothelial carcinoma: A systematic review.

OBJECTIVES: The role of adjuvant radiotherapy (ART) in patients with bladder cancer (BCa) and upper tract urothelial carcinoma (UTUC) is controversial. We systematically evaluated the oncologic efficacy of ART and its associated toxicity in patients treated with surgery and ART for BCa and UTUC. MATERIALS AND METHOD: We performed a literature search on December 2018 using MEDLINE, Web of Science, Cochrane databases and Scopus according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Fourteen BCa studies and 14 UTUC studies were included in this systematic review. The data were too scarce and heterogeneous for meta-analytical analysis. RESULTS: The quality and quantity of the data on ART in BCa and UTUC patients are limited. The combination of ART and chemotherapy appears to be beneficial in patients with locally advanced BCa or UTUC. The early and late adverse effects of ART are decreasing reflecting the progress in radiation technology. CONCLUSIONS: According to the currently available literature, there is no clear benefit of ART after radical surgery in BCa and UTUC. Future efforts should focus on evaluating multimodal approach using ART with chemotherapy. Until that time comes, ART should be used carefully in patients with BCa and UTUC on a case-by-case basis.

Methylation of SPARCL1 Is Associated with Oncologic Outcome of Advanced Upper Urinary Tract Urothelial Carcinoma.

Advanced upper urinary tract urothelial carcinoma (UTUC) is often associated with poor oncologic outcomes. The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) protein, belongs to the SPARC-related family of matricellular proteins. Much literature has been published describing the role of SPARCL1 in the prognosis many cancers. In this study, methylated promoter regions in high-grade and high-stage upper urinary urothelial tumours compared with normal urothelium were analyzed and revealed that SPARCL1 was the most significantly hypermethylated gene in UTUC tissues. Then we prospectively collected UTUC samples and adjacent normal urothelium for pyrosequencing validation, identifying significant CpG site methylation in UTUC tissues. In addition, SPARCL1 RNA levels were significantly lower in UTUC samples. Multivariate Cox regression analysis from 78 patients with solitary renal pelvic or ureteral pT3N0M0 urothelial carcinomas revealed that only negative SPARCL1 expression and nonpapillary tumour architecture were independently associated with systemic recurrence (p = 0.011 and 0.008, respectively). In vitro studies revealed that the behaviour of BFTC-909 cells was less aggressive and more sensitive to radiation or chemotherapy after SPARCL1 overexpression. Thus, SPARCL1 could be considered as a prognostic marker and help decision-making in clinical practice.

Panorama des tumeurs urologiques au CNHU-HKM de Cotonou

Introduction : Les tumeurs urologiques sont très fréquentes dans la pratique courante de l'Urologie et constitue l'essentiel de l'activité de l'urologue Objectifs : Etudier les aspects épidémiologiques et évolutives des tumeurs urologiques à la Clinique Universitaire d'Urologie-Andrologie du CNHU HKM de Cotonou Patients et Méthodes : Il s'agissait d'une étude rétrospective et descriptive des aspects épidémiologiques et évolutives des tumeurs urologiques reçues au CNHU-HKM de Cotonou sur la période allant du 1er janvier 2008 au 31 décembre 2017. Les paramètres étudiés étaient : l'âge, le sexe des patients, le diagnostic, la localisation et la nature suspectée de la tumeur, le délai de recours aux soins et la mortalité hospitalière Résultats : 1047 dossiers ont été colligés. La majorité (82,14%) de nos patients ont un âge supérieur à 50 ans. Les hommes sont majoritairement atteints avec un taux de 92,36%. La sex-ratio est de 0,92 en faveur des hommes H/F. La majorité de nos patients (87,68%) avait vu leurs symptomatologies évoluer plus de 6 mois avant de recourir aux soins médicaux. Un total de 532 patients avait une tumeur bénigne et 515, une tumeur maligne. La glande prostatique est l'organe génital masculin le plus affecté. Les tumeurs prostatiques représentent 75, 54% des tumeurs uro-génitaux dont 43,83% bénignes et 31,70% malignes. Conclusion : Les tumeurs urogénitales sont des affections fréquentes dominées par les tumeurs de la prostate, de la vessie et des reins. Au Bénin, elles sont diagnostiquées tardivement

Practice-changing radiation therapy trials for the treatment of cancer: where are we 150 years after the birth of Marie Curie?

As we mark 150 years since the birth of Marie Curie, we reflect on the global advances made in radiation oncology and the current status of radiation therapy (RT) research. Large-scale international RT clinical trials have been fundamental in driving evidence-based change and have served to improve cancer management and to reduce side effects. Radiation therapy trials have also improved practice by increasing quality assurance and consistency in treatment protocols across multiple centres. This review summarises some of the key RT practice-changing clinical trials over the last two decades, in four common cancer sites for which RT is a crucial component of curative treatment: breast, lung, urological and lower gastro-intestinal cancer. We highlight the global inequality in access to RT, and the work of international organisations, such as the International Atomic Energy Agency (IAEA), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the United Kingdom National Cancer Research Institute Clinical and Translational Radiotherapy Research Working Group (CTRad), that aim to improve access to RT and facilitate radiation research. We discuss some emerging RT technologies including proton beam therapy and magnetic resonance linear accelerators and predict likely future directions in clinical RT research.

Radiotherapy-related complications presenting to a urology department: a more common problem than previously thought?

OBJECTIVE: To quantify the burden of the side effects of radiotherapy on a tertiary referral urology department. PATIENTS AND METHODS: A prospective study of all urology admissions to a public urology department at a tertiary hospital in a 6-month period was performed. Patients admitted with complications attributable to radiotherapy were included in the study. Data obtained included patient demographics, radiotherapy details, complication type and management required. RESULTS: A total of 1198 patients were admitted; 921 (77%) were elective and 277 (23%) were emergency admissions. Thirteen out of the 921 (1.4%) elective admissions and 20 out of the 277 (7.2%) emergency admissions were attributable to radiotherapy complications. Radiotherapy complications was the fourth most common reason for emergency admission, ahead of acute urinary retention. These 33 admissions were accounted for by 21 patients. A total of 39 separate complications attributable to radiotherapy were diagnosed, with some patients having multiple complications. The median (interquartile range) time to onset of complications was 4 (1-9) years. The surgical intervention rate was 67%. The commonest procedures were washout with/without clot evacuation or diathermy in theatre (15.8%) and urethral dilatation/bladder neck incision (15.8%). Two urinary diversions and two cystoprostatectomies plus urinary diversion were performed. CONCLUSION: Radiotherapy complications are consequential and account for a substantial proportion of a tertiary urology department's emergency workload. These complications generally occur years after radiotherapy and frequently require surgical intervention.

Análisis de impacto presupuestal de radioterapia para el tratamiento de cánceres del sistema urinario en Colombia / Budget impact analysis of radiotherapy for the treatment of cancers of the urinary system in Colombia

INTRODUCCIÓN: El análisis de impacto presupuestal (AIP) de radioterapia para el tratamiento de cánceres del sistema urinario en Colombia, se desarrolló en el marco del mecanismo técnicocientífico para la ampliación progresiva del Plan de Beneficios en Salud con cargo a la UPC (PBSUPC) y la definición de la lista de exclusiones, establecido en el artículo 15 de la Ley 1751 de 2015. Estas tecnologías fueron seleccionadas por la Dirección de Beneficios, Costos y Tarifas del Aseguramiento en Salud del Ministerio de Salud y Protección Social (MinSalud), y remitidas al Instituto de Evaluación Tecnológica en Salud (IETS) para su evaluación. Los carcinomas uroteliales (CU) son los cuartos tumores más comunes (1). Pueden ubicarse en las vías urinarias inferiores (vejiga y uretra) o superiores (cavidades pialeocíclicas y uréter). Los tumores de la vejiga representan el 90-95% de los CU y son la malignidad más común de las vías urinarias. En las estimaciones reportadas por Globocan 2012, sólo están disponibles los datos epidemiológicos para el cáncer de riñón y cáncer de vejiga. La tasa de incidencia ajustada por edad a nivel mundial en ambos sexos para el cáncer de riñón es de 2,4 por 100.000 habitantes y para cáncer de vejiga de 3,1 por 100.000 (4). La tasa de mortalidad para el cáncer de riñón es del 1,7 por 100.000 y para el cáncer de vejiga del 2,0 por 100.000 habitantes. En Colombia, de acuerdo a las estimaciones realizadas por el Instituto Nacional de Cancerología (INC) para el periodo de 2007 a 2011, la tasa de incidencia ajustada por edad de cáncer de riñón coincide con la reportada por GLOBOCAN 2012, y la tasa de incidencia ajustada por edad de cáncer de vejiga es ligeramente mayor en los hombres colombianos (3,9 por 100.000 habitantes). En las mujeres, las tasas de incidencia ajustadas por edad para el cáncer de vejiga y cáncer de riñón son menores en comparación con los hombres (TAE de 1,2 por 100.000 para cáncer de vejiga y TAE de 1,9 por 100.000 para cáncer de riñón). La radioterapia tiene un impacto en el control locorregional y en la supervivencia global y por causa específica en muchos tumores primarios; sin embargo, su uso ha implicado un riesgo real de efectos secundarios agudos y crónicos que potencialmente pueden, en casos seleccionados, traducirse en una morbi-mortalidad importante y/o reducir la calidad de vida de los pacientes. Actualmente en el plan de beneficios del Sistema General de Seguridad Social en Salud (SGSSS) en Colombia, únicamente la radioterapia Conformacional 3D (3D CRT) está indicada para el manejo del cáncer gástrico; sin embargo, su uso también es requerido en cánceres del sistema urinario como cáncer de la pelvis renal, vejiga y uréteres. El objetivo del presente AIP es estimar el esfuerzo financiero necesario para la adopción de la radioterapia 3D CRT en el tratamiento de los cánceres del sistema urinario, en un horizonte temporal de tres años. TECNOLOGÍAS EVALUADAS: Tratamiento actual: Para la realización del presente documento se ha considerado que a pesar de que la radioterapia convencional 2D aún se encuentra incluida en el Plan de Beneficios en Salud con cargo a la UPC (PBSUPC), su capacidad técnica no es comparable con la radioterapia conformada tridimensional (3D CRT) para el tratamiento del cáncer de vejiga, cáncer de la pelvis renal y cáncer de uréteres, por tanto no existe una tecnología de radioterapia comparable en el sistema de salud colombiano. Tanto las guías de práctica internacionales como las sociedades científicas incluyen dentro de sus recomendaciones la radioterapia 3D CRT para el manejo de las neoplasias. El concepto de radioterapia 3D CRT, que contempla tratamientos con intención radical, incremento de dosis postoperatoria y volúmenes críticos a órganos cercanos, entre otras, ha sucedido a las planificaciones realizadas hasta ahora en solo dos dimensiones del espacio (2D). El concepto de radioterapia 3D CRT, que contempla tratamientos con intención radical, incremento de dosis postoperatoria y volúmenes críticos a órganos cercanos, entre otras, ha sucedido a las planificaciones realizadas hasta ahora en solo dos dimensiones del espacio (2D). considerando antecedentes irrefutables de la radioterapia, que en general propende por dosis más altas de irradiación para incrementar el control loco-regional de la enfermedad, que se traduce a su vez en aumentos de la supervivencia y dosis más altas de irradiación disminuyendo la incidencia de efectos secundarios a largo plazo. En Colombia, el INC, referente nacional para el manejo del cáncer y sus complicaciones, ha excluido la radioterapia convencional 2D de sus protocolos, y ha emitido las recomendaciones específicas para radioterapia de Intensidad Modulada (IMRT) y la radioterapia 3D CRT. De acuerdo a los lineamientos de manejo del INC, los cánceres del sistema urinario deben manejarse con radioterapia 3D CRT. En este sentido, se considera el uso de radioterapia convencional 2D como práctica de tratamiento para casos de Urgencias oncológicas de Radioterapia y como radioterapia neoadyuvante hasta dosis límite permitida con el compromiso de remisión de ese paciente a las instituciones que ofrezcan tecnología avanzada como 3D CRT e IMRT para que complete el tratamiento del paciente. Teniendo en cuenta que el PBSUPC incluye la radioterapia convencional 2D, para efectos del análisis de impacto presupuestal se incluye la radioterapia 2D como tratamiento actual, a pesar de las consideraciones expresadas previamente. TECNOLOGÍA EVALUADA: De acuerdo a la consulta de expertos y revisión de guías de práctica clínica, en la actualidad se utiliza la radioterapia 3D CRT para el tratamiento de los cánceres del sistema urinario como el cáncer de vejiga, cáncer de la pelvis renal y cáncer de uréteres. Sin embargo, en el PBSUPC está tecnología no está indicada para este tipo de cánceres. Considerando este escenario, la tecnología a evaluar será la radioterapia 3D CRT. INSUMOS Y MÉTODOS: Esta sección presenta los supuestos, parámetros y métodos utilizados para el modelo de estimación del impacto presupuestal describiendo la siguiente información: Perspectiva: Se abordó la perspectiva del tercer pagador el cual corresponde al Sistema General de Seguridad Social en Salud (SGSSS). Horizonte temporal: El horizonte temporal utilizado corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión de la radioterapia 3D CRT en la financiación con recursos públicos asignados a la salud en el año 1. Población total: Corresponde a la población de todas las edades, reportada en la Base de Datos Única de Afiliados (BDUA) de 2016. A partir de esta población se estimó la población objetivo, por medio de tasas de incidencia de los diferentes tipos de cánceres del sistema urinario. Modelo: Se desarrolló un modelo de impacto presupuestal, donde dada la distribución de mercado actual y la indicación de radioterapia para los cánceres del sistema urinario, se plantean dos escenarios con una cobertura total de la nueva tecnología. Los impactos vienen acompañados de análisis de sensibilidad univariados. Resultados: Dado que la tecnología de la radioterapia 3D CRT corresponde al tratamiento nuevo y es el manejo estándar actual según expertos clínicos, se planteó una cobertura del 100% para los dos escenarios incluidos.

A phase I/II trial of fixed-dose stereotactic body radiotherapy with sequential or concurrent pembrolizumab in metastatic urothelial carcinoma: evaluation of safety and clinical and immunologic response.

BACKGROUND: Current first-line standard of therapy for metastatic urothelial carcinoma is platinum-based combination chemotherapy. Pembrolizumab in phase III has demonstrated a promising overall response rate of 21.1% in patients with progression or recurrence after platinum-based chemotherapy. Preclinical and clinical evidence suggests that radiotherapy has a systemic anti-cancer immune effect and can increase the level of PD-L1 and tumor infiltrating lymphocytes in the tumor microenvironment. These findings gave rise to the hypothesis that the combination of radiotherapy with anti-PD1 treatment could lead to a synergistic effect, hereby enhancing response rates. METHODS: The phase I part will assess the dose limiting toxicity of the combination treatment of stereotactic body radiotherapy (SBRT) with four cycles of pembrolizumab (200 mg intravenously, every 3 weeks) in patients with metastatic urothelial carcinoma. The dose of both pembrolizumab and SBRT will be fixed, yet the patients will be randomized to receive SBRT either before the first cycle of pembrolizumab or before the third cycle of pembrolizumab. SBRT will be delivered (24 Gy in 3 fractions every other day) to the largest metastatic lesion. Secondary objectives include response rate according to RECIST v1.1 and immune related response criteria, progression-free survival and overall survival. The systemic immune effect triggered by the combination therapy will be monitored on various time points during the trial. The PD-L1/TIL status of the tumors will be analyzed via immunohistochemistry and response rates in the subgroups will be analyzed separately. A Simon's two-stage optimum design is used to select the treatment arm associated with the best response rate and with acceptable toxicity to proceed to the phase II trial. In this phase, 13 additional patients will be accrued to receive study treatment. DISCUSSION: The progress made in the field of immunotherapy has lead to promising breakthroughs in various solid malignancies. Unfortunately, the majority of patients do not respond. The current trial will shed light on the toxicity and potential anti-tumor activity of the combination of radiotherapy with anti-PD1 treatment and may identify potential new markers for response and resistance to therapy. Trial registration this trial is registered on clinicaltrials.gov (NCT02826564).

Consolidative Radiotherapy in Metastatic Urothelial Cancer.

BACKGROUND: We report outcomes of a retrospective, single-institution experience with consolidative radiation after chemotherapy in metastatic urothelial cancer (MUC). PATIENTS AND METHODS: From our single-institution database of 2597 patients with urothelial carcinoma treated since 1997, we identified 22 patients with MUC who underwent consolidative radiotherapy after a partial response to chemotherapy with the intent of rendering them disease-free. All patients had undergone primary surgical therapy with either cystectomy or nephroureterectomy. Progression-free survival (PFS) was defined as time from completion of radiation therapy to relapse or last follow-up. Overall survival (OS) was defined as time from start of chemotherapy to death or last follow-up. RESULTS: In the selected group of patients with MUC, the median age was 67 years; 59% had received previous cisplatin-based chemotherapy. The most common sites radiated were the regional lymph nodes (64%). Other radiated sites included the lung, adrenal glands, and omental metastases. Median survival from diagnosis to cystectomy was 48 months. Median PFS was 13 months and median OS was 29 months. Eight patients (36%) were alive and disease-free 6 years after radiation therapy. Patients who were rendered disease-free were those with nodal metastases and delivery of radiation to a single site of metastasis. CONCLUSION: In this highly selective cohort of patients with MUC treated with consolidative radiation after chemotherapy, 36% were rendered disease-free. This suggests that radiation is feasible and might contribute to long-term disease control. Further prospective studies are needed to better characterize the benefit of combined modality treatment.

The effectiveness of hyperbaric oxygen therapy (HBOT) in radiation-induced haemorrhagic cystitis.

INTRODUCTION: Radiation cystitis is one of the possible complications from pelvic radiotherapy. Hyperbaric oxygen (HBOT) improves tissue oxygenation and healing of scarred tissue. AIMS: To assess the efficacy of hyperbaric oxygen therapy (HBOT) in the management of radiation-induced haemorrhagic cystitis in patients with urological cancers. METHODS: This is a retrospective review on all patients with macroscopic haematuria secondary to radiation induced haemorrhagic cystitis who were treated with hyperbaric oxygen therapy (HBOT) between 2009 and 2013. The primary outcome is symptomatic assessment (either complete resolution, partial resolution or no change). RESULTS: A total of 12 patients with radiation-induced cystitis secondary to urological cancer were included in this study with a mean follow-up of 443 days. The mean age was 78 years. Complete resolution of haematuria was seen in six out of 12 patients. Partial response was achieved in two patients where one required two courses of HBOT and one required three courses of HBOT. As a result, the overall improvement of haematuria after HBOT was 67%. A total of four patients had no response to HBOT. CONCLUSION: Radiation-induced cystitis is a difficult clinical problem to treat. HBOT is not a magic bullet but it may be another alternative treatment option we have at this point in time.

[Good practice of image-guided radiotherapy]. / Bonnes pratiques de radiothérapie guidée par l'image.

Image-guided radiotherapy (IGRT) aims to take into account the anatomical variations occurring during the course of radiotherapy, by direct or indirect visualization of the target volume followed by a corrective action. The movements of the target, or at least the set-up errors are corrected by moving the treatment table, corresponding to the simplest and most validated IGRT modality in a standard practice. The deformations of the target volume and organs at risk are however much more common, and unfortunately much more complicated to consider, requiring multiple planning before or during the treatment, corresponding to the adaptive radiotherapy strategies. The planning target volume must be carefully chosen according to these anatomic variations. This article reviews the modalities of IGRT, standard or under evaluation, according to the different tumour sites.