Salvage Treatment of Refractory HSV Oral Lesions with Pritelivir in Allogeneic Hematopoietic Cell Transplant Recipients.

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.

State of the art and future challenges of urethra-sparing stereotactic body radiotherapy for prostate cancer: a systematic review of literature.

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.

Postoperative radiotherapy for meningiomas - a decision-making analysis.

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.

Cone-beam computed tomography-based radiomics in prostate cancer: a mono-institutional study.

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.

The role of radiosurgery in trigeminal neuralgia.

A short review of clinical use of radiosurgery in trigeminal neuralgia is offered.

Adjuvant intraoperative radiotherapy for selected breast cancers in previously irradiated women: Evidence for excellent feasibility and favorable outcomes.

BACKGROUND: The present report provides preliminary outcomes with intraoperative radiotherapy delivered to women with breast cancer included in a re-irradiation program. MATERIALS AND METHODS: From October 2010 to April 2014, thirty women were included in a re-irradiation protocol by exploiting IORT technique. The median time between the two irradiations was 10 years (range 3-50). All patients underwent conservative surgery, sentinel lymph node excision and IORT with electron beam delivered by a mobile linear accelerator. Primary endpoint was esthetic result and consequential/late toxicity; secondary endpoints were local control (LC), disease free survival (DFS) and overall survival (OS). RESULTS: With a median follow up of 47 months (range 10-78), we analyzed 29 patients (1 lost at follow up). Twenty-seven patients (90%) had presented breast cancer local relapse or a new primary cancer in the same breast after a previous conservative surgery plus radiation treatment; three patients (10%) had previously received irradiation with mantle field for Hodgkin Lymphoma. Esthetic result was excellent in 3 pts (10%), good in 12 pts (41%), fair in 8 pts (28%) and poor in 6 pts (21%). 12 (41%) patients showed subcutaneous fibrosis at the last follow-up. LC, DFS and OS at five years was 92.3%, 86.3% and 91.2%, respectively. CONCLUSION: Although we analyzed a small number of patients, our results are satisfactory and this approach is feasible even if it could not be considered the standard treatment. Further clinical trials exploring IORT are needed to identify possible subgroups of patients that might be suitable for this type of approach.

Challenges of antimicrobial stewardship among older adults.

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.

Impact of intermittent versus continuous infusions on central line-associated bloodstream infection risk in haemato-oncology patients: a quasi-experimental study.

BACKGROUND: Continuous fluid infusions delivered between therapies by piggy-back systems avoid disconnection and reconnection of central venous catheters (CVC), thereby reducing opportunities for line contamination. However, the impact of continuous versus intermittent infusions on central line-associated bloodstream infections (CLABSI) is unknown. AIM: To investigate the effect of temporary infusion interruption and line disconnection, with or without use of a 70% isopropyl alcohol cap (IPA-C) use on CLABSI rates in haematology patients. METHODS: Quasi-experimental study in two haemato-oncology units. At baseline (P1, September 2020 - August 2021), continuous intravenous piggy-back infusions were mandatory. In a first intervention phase (P2, September 2021 - August 2022), infusion disconnections were implemented with use of a 70% isopropyl alcohol cap (IPA-C) for passive decontamination. In a second intervention phase (P3, September 2022 - August 2023), infusion disconnections continued without the use of IPA-C. Rates of CLABSI were compared across the three intervention periods using segmented Poisson regression. FINDINGS: A total of 11,039 catheter-days across 764 CVC and 16,226 patient-days were included. 21 CLABSI were recorded across all intervention periods. Compared with P1, incidence rate ratios (IRRs) for CLABSI did not significantly change in P2 (IRR 0.76 [95% CI 0.27-2.15]) and P3 (IRR 0.79 [CI 95% 0.28-2.22]). No CVCs were removed due to occlusion during the study period. Five of 21 CLABSI were polymicrobial, and coagulase-negative staphylococci were isolated in 19/21 cases (90%). CONCLUSION: Interruption of continuous infusions in haemato-oncology patients with a CVC was not associated with a substantial change in CLABSI rates, whether or not an IPA-C was used.

Multi-institutional Analysis of Metastasis-directed Therapy with or Without Androgen Deprivation Therapy in Oligometastatic Castration-sensitive Prostate Cancer.

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.

Erectile function preservation after salvage radiation therapy for biochemically recurrent prostate cancer after prostatectomy: Five-year results of the SAKK 09/10 randomized phase 3 trial.

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.

Multifocal branch-duct intraductal papillary mucinous neoplasms (IPMNs) of the pancreas: magnetic resonance (MR) imaging pattern and evolution over time.

PURPOSE: The aim of our study was to follow the evolution over time of multifocal intraductal papillary mucinous neoplasms (IPMN) of the pancreatic duct side branches by means of magnetic resonance imaging (MRI). MATERIALS AND METHODS: A total of 155 patients with multifocal IPMN of the side branches were examined with MRI and MR cholangiopancreatography (MRI/MRCP). Inclusion criteria were patients with ≥2 dilated side branches involving any site of the parenchyma; presence of communication with the main pancreatic duct and previous investigations by MRI/MRCP within at least six months. Median follow-up was 25.8 months (range, 12-217). Patients with a follow-up period shorter than 12 months (n=33) and those with a diagnosis of multifocal IPMN of the side branches without any follow-up (n=14) were excluded from the study. The final study population thus comprised 108 patients. A double, quantitative and qualitative, analysis was carried out. The quantitative image analysis included: number of dilated side branches in the head-uncinate process and body-tail; maximum diameter of lesions in the head-uncinate process; maximum diameter in the body-tail; maximum diameter of the main pancreatic duct in the head and body-tail. The qualitative image analysis included: presence of malformations or anatomical variants of the pancreatic ductal system; site of the lesions (head-uncinate process, body-tail, ubiquitous, bridge morphology); presence of gravity-dependent intraluminal filling defects; presence of enhancing mural nodules. RESULTS: At diagnosis, the mean number of cystic lesions of the side branches was 7.09. The mean diameter of the cystic lesions was 13.7 mm. The mean diameter of the main pancreatic duct was 3.6 mm. At follow-up, the mean number of cystic lesions was 7.76. The mean diameter of the cystic lesions was 13.9 mm. The mean diameter of the main pancreatic duct was 3.7 mm. Intraluminal filling defects in the side branches were seen in 18/108 patients (16.6%); enhancing mural nodules were seen in 3/108 patients (2.7%). CONCLUSIONS: Multifocal IPMN of the branch ducts shows a very slow growth and evolution over time. In our study, only 3/108 patients showed mural nodules which, however, did not require any surgical procedure, indicating that careful nonoperative management may be safe and effective in asymptomatic patients.

Invasive Aspergillosis and the Impact of Azole-resistance.

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.

Atypical pulmonary phaeohyphomycosis due to Aureobasidium spp. - case report and brief literature review.

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.

Risk Factors and Incidence of Sexually Transmitted Infections in the Swiss HIV Cohort Study.

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.

Adherence to Contouring and Treatment Planning Requirements Within a Multicentric Trial: Results of the Quality Assurance of the SAKK 09/10 trial.

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.

Two Birds with One Stone: Skull Base Meningioma and Jugulotympanic Paragangliomas with Somatostatin Receptor Positron Emission Tomography.

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.