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Objectives: To evaluate effects of dose intensified salvage radiotherapy (sRT) on erectile function in biochemically recurrent prostate cancer (PC) after radical prostatectomy (RP). Materials and methods: Eligible patients had evidence of biochemical failure after RP and a PSA at randomization of ≤ 2 ng/ml. Erectile dysfunction (ED) was investigated as secondary endpoint within the multicentre randomized trial (February 2011 to April 2014) in patients receiving either 64 Gy or 70 Gy sRT. ED and quality of life (QoL) were assessed using CTCAE v4.0 and the EORTC QoL questionnaires C30 and PR25 at baseline and up to 5 years after sRT. Results: 344 patients were evaluable. After RP 197 (57.3 %) patients had G0-2 ED while G3 ED was recorded in 147 (42.7 %) patients. Subsequently, sexual activity and functioning was impaired. 5 years after sRT, 101 (29.4 %) patients noted G0-2 ED. During follow-up, 44.2 % of patients with baseline G3 ED showed any improvement and 61.4 % of patients with baseline G0-2 ED showed worsening. Shorter time interval between RP and start of sRT (p = 0.007) and older age at randomization (p = 0.005) were significant predictors to more baseline ED and low sexual activity in the long-term. Age (p = 0.010) and RT technique (p = 0.031) had a significant impact on occurrence of long-term ED grade 3 and worse sexual functioning. During follow-up, no differences were found in erectile function, sexual activity, and sexual functioning between the 64 Gy and 70 Gy arm. Conclusion: ED after RP is a known long-term side effect with significant impact on patients' QoL. ED was further affected by sRT, but dose intensification of sRT showed no significant impact on erectile function recovery or prevalence of de novo ED after sRT. Age, tumor stage, prostatectomy and RT-techniques, nerve-sparing and observation time were associated with long-term erectile function outcome.ClinicalTrials.gov. Identifier: NCT01272050.
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BACKGROUND: Metastasis-directed therapy (MDT) is increasingly being used in oligometastatic castration-sensitive prostate cancer (omCSPC). However, it is currently unclear how to optimally integrate MDT with the standard of care of systemic hormonal therapy. OBJECTIVE: To report long-term outcomes of MDT alone versus MDT and a defined course of androgen deprivation therapy (ADT) in omCSPC. DESIGN, SETTING, AND PARTICIPANTS: Here, a multicenter, international retrospective cohort of omCSPC as defined by conventional imaging was reported. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biochemical progression-free survival (bPFS), distant progression-free survival (dPFS), and combined biochemical or distant progression-free survival (cPFS) were evaluated with Kaplan-Meier and multivariable Cox proportional hazard regression models. RESULTS AND LIMITATIONS: A total of 263 patients were included, 105 with MDT + ADT and 158 with MDT alone. The majority of patients had metachronous disease (90.5%). Five-year bPFS, dPFS, and cPFS were, respectively, 24%, 41%, and 19% in patients treated with MDT + ADT and 11% (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.36-0.64), 29% (HR 0.56, 95% CI 0.40-0.78), and 9% (HR 0.50, 95% CI 0.38-0.67) in patients treated with MDT alone. On a multivariable analysis adjusting for pretreatment variables, the use of ADT was associated with improved bPFS (HR 0.43, p < 0.001), dPFS (HR 0.45, p = 0.002), and cPFS (HR 0.44, p < 0.001). CONCLUSIONS: In this large multi-institutional report, the addition of concurrent ADT to MDT appears to improve time to prostate-specific antigen progression and distant recurrence, noting that about 10% patients had durable control with MDT alone. Ongoing phase 3 studies will help further define treatment options for omCSPC. PATIENT SUMMARY: Here, we report a large retrospective review evaluating the outcomes of metastasis-directed therapy with or without a limited course of androgen deprivation for patients with oligometastatic castration-sensitive prostate cancer. This international multi-institutional review demonstrates that the addition of androgen deprivation therapy to metastasis-directed therapy (MDT) improves progression-free survival. While a proportion of patients appear to have long-term disease control with MDT alone, further work in biomarker discovery is required to better identify which patients would be appropriate for de-escalated therapy.
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Older adults hospitalized in internal medicine wards or long-term care facilities (LTCF) are progressively increasing. Older adults with multimorbidity are more susceptible to infections, as well as to more vulnerable to adverse effects (and interactions) of antibiotics, resulting in a need for effective and safer strategies for antimicrobial stewardship (ASM), both in hospitalization wards and long-term care facilities. Studies on antimicrobial stewardship in older patients are scarce and guidelines are required. Given the peculiarities of the optimization of antimicrobial prescription in individual older adults for common infections, tactics to overcome barriers need an update. The use of rapid diagnosis tests, biomarkers, de-escalation and switching from intravenous to oral/subcutaneous therapy strategies are examples of successful AMS interventions. AMS interventions are associated with reduced side effects, lower mortality, shorter hospital stays, and reduced costs. The proposed AMS framework in LTCF should focus on five domains: strategic vision, team, interventions, patient-centred care and awareness. Internists can partner with geriatrists, pharmacists and infectious disease specialists to address barriers and to improve patient care.
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Antibacterianos , Programas de Optimización del Uso de los Antimicrobianos , Humanos , Anciano , Antibacterianos/uso terapéutico , Cuidados a Largo Plazo , Hospitalización , Medicina Interna , Atención Dirigida al PacienteRESUMEN
PURPOSE: Doses delivered to the urethra have been associated with an increased risk to develop long-term urinary toxicity in patients undergoing stereotactic body radiotherapy (SBRT) for prostate cancer (PCa). Aim of the present systematic review is to report on the role of urethra-sparing SBRT (US-SBRT) techniques for prostate cancer, with a focus on outcome and urinary toxicity. METHOD: A systematic review of the literature was performed on the PubMed database on May 2023. Based on the urethra-sparing technique, 13 studies were selected for the analysis and classified in the two following categories: "urethra-steering" SBRT (restriction of hotspots to the urethra) and "urethra dose-reduction" SBRT (dose reduction to urethra below the prescribed dose). RESULTS: By limiting the urethra Dmax to 90GyEQD2 (α/ß = 3 Gy) with urethra-steering SBRT techniques, late genitourinary (GU) grade 2 toxicity remains mild, ranging between 12.1% and 14%. With dose-reduction strategies decreasing the urethral dose below 70 GyEQD2, the risk of late GU toxicity was further reduced (< 8% at 5 years), while maintaining biochemical relapse-free survival rates up to 93% at 5 years. CONCLUSION: US-SBRT techniques limiting maximum doses to urethra below a 90GyEQD2 (α/ß = 3 Gy) threshold result in a low rate of acute and late grade ≥ 2 GU toxicity. A better understanding of clinical factors and anatomical substructures involved in the development of GU toxicity, as well as the development and use of adapted dose constraints, is expected to further reduce the long-term GU toxicity of prostate cancer patients treated with SBRT.
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Neoplasias de la Próstata , Radiocirugia , Masculino , Humanos , Uretra , Radiocirugia/efectos adversos , Radiocirugia/métodos , Recurrencia Local de Neoplasia/etiología , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/etiología , Sistema UrogenitalRESUMEN
Purpose of Review: IA (invasive aspergillosis) caused by azole-resistant strains has been associated with higher clinical burden and mortality rates. We review the current epidemiology, diagnostic, and therapeutic strategies of this clinical entity, with a special focus on patients with hematologic malignancies. Recent Findings: There is an increase of azole resistance in Aspergillus spp. worldwide, probably due to environmental pressure and the increase of long-term azole prophylaxis and treatment in immunocompromised patients (e.g., in hematopoietic stem cell transplant recipients). The therapeutic approaches are challenging, due to multidrug-resistant strains, drug interactions, side effects, and patient-related conditions. Summary: Rapid recognition of resistant Aspergillus spp. strains is fundamental to initiate an appropriate antifungal regimen, above all for allogeneic hematopoietic cell transplantation recipients. Clearly, more studies are needed in order to better understand the resistance mechanisms and optimize the diagnostic methods to identify Aspergillus spp. resistance to the existing antifungal agents/classes. More data on the susceptibility profile of Aspergillus spp. against the new classes of antifungal agents may allow for better treatment options and improved clinical outcomes in the coming years. In the meantime, continuous surveillance studies to monitor the prevalence of environmental and patient prevalence of azole resistance among Aspergillus spp. is absolutely crucial.
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We present two allogeneic hematopoietic cell transplantation recipients (HCTr) treated with pritelivir for acyclovir-resistant/refractory (r/r) HSV infection based on the expanded access program of the pritelivir manufacturer. Outpatient treatment with pritelivir was administered, with partial response by week 1 of treatment and complete response by week 4 of treatment in both patients. No adverse events were noted. Pritelivir appears to be an effective and safe option for the management of acyclovir-r/r HSV infections in highly immunocompromised patients in an outpatient setting.
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Trasplante de Células Madre Hematopoyéticas , Herpes Simple , Humanos , Antivirales , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Terapia Recuperativa , Receptores de Trasplantes , Herpes Simple/tratamiento farmacológico , Herpes Simple/inducido químicamente , Aciclovir/uso terapéuticoRESUMEN
We report on a case of probable invasive Auerobasidium spp. pulmonary infection in a patient with myelodysplastic syndrome. The patient was successfully treated with liposomal amphotericin B monotherapy, with transition to orally administered isavuconazole. This case shows an atypical initial radiological presentation with diffuse ground-glass opacities, as previously demonstrated in cases of Aureobasidium spp. hypersensitivity pneumonitis. Moreover this case further highlights the difficulties associated with the diagnosis and complexity in the management of Aureobasidium spp. infections.
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Antifúngicos , Feohifomicosis , Humanos , Antifúngicos/uso terapéutico , Aureobasidium , Feohifomicosis/diagnóstico , Feohifomicosis/tratamiento farmacológico , Pulmón/diagnóstico por imagenRESUMEN
Background: Sexually transmitted infections (STIs) are common among people with human immunodeficiency virus (PWH), but there are limited data about risk factors and incidence of STIs in large, representative cohort studies. Methods: We assessed incidence and risk factors of STIs reported by treating physicians within the Swiss HIV Cohort Study (SHCS). Sexually transmitted infections and demographic, clinical, and behavioral characteristics were prospectively collected at 6-month follow-up visits between October 2017 and November 2019. We used multilevel Poisson regression to assess incidence rate ratios of different STIs. Results: Among 10 140 study participants, a total of 1634 STIs in 1029 SHCS participants were reported over 17 766 person-years of follow up (PYFUP). The overall incidence of any reported STI was 91.9 per 1000 PYFU (95% confidence interval [CI], 85.8 -98.5). Among the 1634 STI episodes, there were 573 (35.1%) incident cases of syphilis, 497 gonorrhea (30.4%), and 418 chlamydia (25.6%). Men who have sex with men (MSM) younger than 50 years represented 21% of the study population, but accounted for 61% of reported STIs. Male sex (adjusted incidence rate ratio [aIRR], 2.03; 95% CI, 1.36-3.02), MSM (aIRR, 3.62; 95% CI, 2.88-4.55), age group 18-34 years (aIRR, 1.78; 95% CI, 1.51-2.10), history of sexual relationships with occasional partners (aIRR, 6.87; 95% CI, 5.40-8.73), and reporting injecting drug use (aIRR, 2.48; 95% CI, 1.91-3.23) were associated with a higher risk of incident STIs. Conclusions: Sexually transmitted infections were frequent among PWH and varied considerably between age and risk groups. Screening programs and recommendations for STI testing need to be adapted according to risk factors and demographic characteristics.
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Próstata , Terapia Recuperativa , Humanos , Ganglios Linfáticos/patología , Masculino , PelvisRESUMEN
BACKGROUND: The management of meningiomas is challenging, and the role of postoperative radiotherapy is not standardized. METHODS: Radiation oncology experts in Swiss centres were asked to participate in this decision-making analysis on the use of postoperative radiotherapy (RT) for meningiomas. Experts from ten Swiss centres agreed to participate and provided their treatment algorithms. Their input was converted into decision trees based on the objective consensus methodology. The decision trees were used as a basis to identify consensus and discrepancies in clinical routine. RESULTS: Several criteria used for decision-making in postoperative RT in meningiomas were identified: histological grading, resection status, recurrence, location of the tumour, zugzwang (therapeutic need to treat and/or severity of symptoms), size, and cell division rate. Postoperative RT is recommended by all experts for WHO grade III tumours as well as for incompletely resected WHO grade II tumours. While most centres do not recommend adjuvant irradiation for WHO grade I meningiomas, some offer this treatment in recurrent situations or routinely for symptomatic tumours in critical locations. The recommendations for postoperative RT for recurrent or incompletely resected WHO grade I and II meningiomas were surprisingly heterogeneous. CONCLUSIONS: Due to limited evidence on the utility of postoperative RT for meningiomas, treatment strategies vary considerably among clinical experts depending on the clinical setting, even in a small country like Switzerland. Clear majorities were identified for postoperative RT in WHO grade III meningiomas and against RT for hemispheric grade I meningiomas outside critical locations. The limited data and variations in clinical recommendations are in contrast with the high prevalence of meningiomas, especially in elderly individuals.
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Neoplasias Meníngeas , Meningioma , Anciano , Niño , Humanos , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirugía , Meningioma/patología , Meningioma/radioterapia , Meningioma/cirugía , Recurrencia Local de Neoplasia/radioterapia , Radioterapia Adyuvante/métodos , Estudios Retrospectivos , SuizaRESUMEN
PURPOSE: To evaluate the results of the radiation therapy (RT) quality assurance (QA) program of the phase 3 randomized SAKK 09/10 trial in patients with biochemically recurrent prostate cancer after prostatectomy. METHODS AND MATERIALS: Within the Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK) 09/10 trial testing 64-Gy versus 70-Gy salvage RT, a central collection of treatment plans was performed and thoroughly reviewed by a dedicated medical physicist and radiation oncologist. Adherence to the treatment protocol and specifically to the European Organization for the Research and Treatment of Cancer (EORTC) guidelines for target volume definition (classified as deviation observed yes vs no) and its potential correlation with acute and late toxicity (Common Terminology Criteria for Adverse Events version 4.0) and freedom from biochemical progression (FFBP) were investigated. RESULTS: The treatment plans for 344 patients treated between February 2011 and April 2014 depicted important deviations from the EORTC guidelines and the recommendations per trial protocol. For example, in up to half of the cases, the delineated structures deviated from the protocol (eg, prostate bed in 48.8%, rectal wall [RW] in 41%). In addition, variations in clinical target volume (CTV) and planning target volume (PTV) occurred frequently (eg, CTV and PTV deviations in up to 42.4% and 25.9%, respectively). The detected deviations showed a significant association with a lower risk of grade ≥2 gastrointestinal acute toxicity when the CTV did not overlap the RW versus when the CTV overlapped the RW (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.22-0.85; P = .014), and a higher rate of grade ≥2 late genitourinary (GU) toxicity when the CTV overlapped the RW (OR, 2.58; 95% CI, 1.17-5.72; P = .019). A marginally significant lower risk of grade ≥2 late GU toxicity was observed when the prostate bed did not overlap versus did overlap the RW (OR, 0.51; 95% CI, 0.25-1.03; P = .06). In addition, a marginally significant decrease in FFBP was observed in patients with PTV not including surgical clips as potential markers of the limits of the prostate bed (hazard ratio, 1.44; 95% CI, 0.96-2.17; P = .07). CONCLUSIONS: Despite a thorough QA program, the central review of a phase 3 trial showed limited adherence to treatment protocol recommendations, which was associated with a higher risk of toxicity by means of acute or late gastrointestinal or GU toxicity and showed a trend toward worse FFBP. Data from this QA review might help to refine future QA programs and prostate bed delineation guidelines.
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Enfermedades Gastrointestinales , Neoplasias de la Próstata , Radioterapia de Intensidad Modulada , Enfermedades Gastrointestinales/etiología , Humanos , Masculino , Prostatectomía , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Radioterapia de Intensidad Modulada/métodos , Recto , Terapia Recuperativa/métodosRESUMEN
We describe the case of a 74-year-old female patient previously treated with radiation therapy for a meningioma of the skull base and with surgery for a right tympanic paraganglioma. After the morphological progression of the meningioma demonstrated by magnetic resonance imaging (MRI), the patient underwent somatostatin receptor positron emission tomography/computed tomography (SR-PET/CT) with Gallium-68 DOTATATE for restaging. This examination showed increased somatostatin receptor expression by the meningioma and confirmed its extension as already assessed by MRI (endocranial extension, skull base involvement and invasion of the right orbit). Furthermore, SR-PET/CT detected two small right jugulotympanic pararagangliomas with high somatostatin receptor expression. Lastly, SR-PET/CT demonstrated that this patient would be an ideal candidate for peptide receptor radionuclide therapy (PRRT) that can be used for the treatment of progressive/treatment-refractory meningiomas and relapsed paragangliomas with high somatostatin receptors expression, both conditions coexisting in this case.
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BACKGROUND: Salvage radiotherapy (SRT) is utilized for biochemical progression of prostate cancer after radical prostatectomy (RP). OBJECTIVE: To report the outcomes of the SAKK 09/10 trial comparing conventional and dose-intensified SRT. DESIGN, SETTING, AND PARTICIPANTS: SAKK 09/10 was a randomized, multicenter, phase 3 trial that recruited men with biochemical progression after RP. INTERVENTION: Patients were randomly assigned to conventional-dose (64 Gy) or dose-intensified SRT (70 Gy) to the prostate bed without hormonal therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was freedom from biochemical progression (FFBP). Secondary endpoints included clinical progression-free survival (PFS), time to hormonal treatment, overall survival (OS), acute and late toxicity (Common Terminology Criteria for Adverse Events v4.0), and quality of life (QoL). RESULTS AND LIMITATIONS: Between February 2011 and April 2014, 350 patients were randomly assigned to 64 Gy (n = 175) or 70 Gy (n = 175). Median prostate-specific antigen at randomization was 0.3 ng/ml. After median follow-up of 6.2 yr, the median FFBP was 8.2 yr in the 64 Gy arm and 7.6 in the 70 Gy arm (log-rank p = 0.4), with a hazard ratio of 1.14 (95% confidence interval 0.82-1.60). The 6-year FFBP rates were 62% and 61%, respectively. No significant differences in clinical PFS, time to hormonal treatment, or OS were observed. Late grade 2 and 3 genitourinary toxicity was observed in 35 (21%) and 13 (7.9%) patients in the 64 Gy arm, and 46 (26%) and seven (4%) in the 70 Gy arm, respectively (p = 0.8). Late grade 2 and 3 gastrointestinal toxicity was observed in 12 (7.3%) and seven patients (4.2%) in the 64 Gy arm, and 35 (20%) and four (2.3%) in the 70 Gy arm, respectively (p = 0.009). There were no significant differences in QoL. CONCLUSIONS: Conventional-dose SRT to the prostate bed is sufficient in patients with early biochemical progression of prostate cancer after RP. PATIENT SUMMARY: The optimal radiation therapy dose for patients who have increased tumor markers after surgery for prostate cancer is unclear. We found that administering a higher dose only increased the gastrointestinal side effects without providing any benefits to the patient. This clinical trial is registered on ClinicalTrials.gov as NCT01272050.
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Recurrencia Local de Neoplasia , Neoplasias de la Próstata , Anciano , Progresión de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/radioterapia , Antígeno Prostático Específico/sangre , Prostatectomía/efectos adversos , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Calidad de Vida , Dosificación Radioterapéutica , Terapia Recuperativa/métodosRESUMEN
PURPOSE: The purpose of the reported study was to investigate the value of cone-beam computed tomography (CBCT)-based radiomics for risk stratification and prediction of biochemical relapse in prostate cancer. METHODS: The study population consisted of 31 prostate cancer patients. Radiomics features were extracted from weekly CBCT scans performed for verifying treatment position. From the data, logistic-regression models were learned for establishing tumor stage, Gleason score, level of prostate-specific antigen, and risk stratification, and for predicting biochemical recurrence. Performance of the learned models was assessed using the area under the receiver operating characteristic curve (AUC-ROC) or the area under the precision-recall curve (AUC-PRC). RESULTS: Results suggest that the histogram-based Energy and Kurtosis features and the shape-based feature representing the standard deviation of the maximum diameter of the prostate gland during treatment are predictive of biochemical relapse and indicative of patients at high risk. CONCLUSION: Our results suggest the usefulness of CBCT-based radiomics for treatment definition in prostate cancer.
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Adenocarcinoma/diagnóstico por imagen , Biología Computacional , Tomografía Computarizada de Haz Cónico/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Aprendizaje Automático , Neoplasias de la Próstata/diagnóstico por imagen , Radioterapia de Intensidad Modulada , Adenocarcinoma/sangre , Adenocarcinoma/patología , Adenocarcinoma/radioterapia , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Curva ROC , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
OBJECTIVE: To evaluate the performance of low dose cone beam CT (CBCT) acquisition protocols for image-guided radiotherapy of prostate cancer. METHODS: CBCT images of patients undergoing prostate cancer radiotherapy were acquired with the settings currently used in our department and two low dose settings at 50% and 63% lower exposure. Four experienced radiation oncologists and two radiation therapy technologists graded the images on five image quality characteristics. The scores were analysed through Visual Grading Regression, using the acquisition settings and the patient size as covariates. RESULTS: The low dose acquisition settings have no impact on the image quality for patients with body profile length at hip level below 100 cm. CONCLUSIONS: A reduction of about 60% of the dose is feasible for patients with size below 100 cm. The visibility of low contrast features can be compromised if using the low dose acquisition settings for patients with hip size above 100 cm. ADVANCES IN KNOWLEDGE: Low dose CBCT acquisition protocols for the pelvis, based on subjective evaluation of patient images.