Short-course Therapy Research Articles

Hypofractionated short-course radiation therapy for recurrent ovarian cancer: A retrospective cohort study

Hypofractionated short-course radiation therapy for recurrent ovarian cancer: A retrospective cohort study

Cost-effectiveness of a short-course antibiotic treatment strategy for the treatment of ventilator-associated pneumonia: an economic analysis of the REGARD-VAP trial

The REGARD-VAP trial showed that individualised shortened antibiotic therapy was non-inferior to usual care for mortality and pneumonia recurrence in patients with ventilator-associated pneumonia (VAP). We aimed to assess the cost-effectiveness of an individualised shortened antibiotic therapy approach in this planned economic analysis. REGARD-VAP was a phase 4, multicentre, open-label, randomised trial to assess a short-course antibiotic treatment strategy for treatment of VAP. In this planned economic analysis, we fitted a decision tree with data from the REGARD-VAP trial to estimate the cost-effectiveness of individualised short-course therapy for VAP, compared to usual care from the health system perspective, in Nepal, Singapore, and Thailand. Incremental cost-effectiveness ratios (ICERs) and incremental net monetary benefits with 95% uncertainty intervals (UIs) were reported against relevant willingness-to-pay thresholds. Parameter uncertainties were evaluated using scenario analyses. A value of information analysis was conducted. Adopting individualised short-course therapy was cost-effective for Nepal (ICER=US$1086; percentage cost-effectiveness=50·3%), Singapore (ICER=-$6069; percentage cost-effectiveness=55·2%), and Thailand (ICER=$263; percentage cost-effectiveness=60·5%). The associated incremental net monetary benefits were $41 (95% UI -2308 to 2390) in Nepal, $5156 (-45 805 to 56 117) in Singapore, and $804 (-6245 to 7852) in Thailand. Value of information analysis showed that reducing uncertainties for mortality probabilities, bed-day costs, and variable costs were valuable for decision making. We found that an individualised short-course antibiotics strategy in patients with VAP is likely to be cost-effective in high-income, middle-income, and low-income settings, although with evident uncertainty. Considered alongside the positive externalities of reduced antimicrobial use, our findings foster confidence in policy makers contemplating adoption of short-course antibiotics. UK Medical Research Council, Singapore National Medical Research Council, and Wellcome Trust.

36 The long-term consequences of short-course systemic corticosteroid therapy for childhood acute asthma exacerbations

Abstract Background Paediatric emergency department (ED) asthma guidelines recommend the administration of short-course systemic corticosteroids (SCS) for moderate to severe asthma exacerbations. The potential adverse implications of frequent, short-course SCS in children are poorly characterized. Objectives To determine the risk of adverse outcomes in children with asthma who receive multiple short-courses of SCS for asthma exacerbation management. Design/Methods In this population-based, retrospective cohort study, we identified children aged 1-16 years with an ED asthma presentation/hospitalization between October 1, 2017, and February 28, 2020. We divided participants into an SCS-exposed and unexposed cohort. A minimum washout period of 3 years was applied to exclude any SCS use before the index date. During a 24-month follow-up period, we captured cumulative short-courses of SCS for acute asthma management and the primary outcome, development of steroid-associated complications. We excluded participants with steroid-treated comorbidities, non-asthma-related SCS exposure and development of adverse outcome(s) before the index visit. We compared baseline characteristics between cohorts using descriptive statistics. A Prentice-Williams-Peterson model was used to determine the risk of adverse outcomes amongst children receiving SCS for asthma management with results expressed as adjusted hazard ratios (HR) and 95% Wald confidence intervals (CI). Results We identified 1468 participants with an asthma ED visit who received ≥1 SCS course for acute management and 541 participants who did not receive SCS during our study window, after applying inclusion/exclusion criteria. Baseline demographics were balanced between cohorts aside from age at index, which was significantly younger (4.31 ± 3.71 vs 7.64 ± 4.21 p<0.001) in the SCS-exposed cohort. Overall, the risk of developing a recurrent SCS-associated adverse outcome was not increased in the SCS-exposed cohort (HR = 0.95, 95% CI: 0.74-1.23, p=0.7). However, when the number of SCS courses was considered, a significant risk of recurrent SCS-associated outcomes emerged, especially for those receiving 4+ SCS courses (HR = 2.30, 95% CI: 0.92-5.80). This potential dose-response effect was negated when patients who were likely on medium to high dose maintenance inhaled corticosteroids, were removed in a sensitivity analysis (HR = 1.38, 95% CI: 0.35-5.39). Conclusion At a tertiary care Canadian paediatric hospital, children and adolescents receiving short-course SCS for asthma exacerbation management overall do not demonstrate an increased risk of developing complications after two years follow-up. However, complication risk may be increased among those receiving 4+ cumulative SCS courses.

Comparative analysis of hypofractionated short-course versus standard radiation therapy in elderly patients with glioblastoma: analysis of nationwide database.

Hypofractionated short-course radiation therapy (SCRT) is an alternative treatment option for elderly or frail patients with newly diagnosed glioblastoma (GBM) post-surgery. This study compares survival outcomes and treatment costs between patients receiving SCRT and those undergoing standard long-course radiation therapy (LCRT). This retrospective study utilized health insurance claims and national cancer registry data from Korea to compare overall survival (OS) and treatment costs between patients receiving SCRT and LCRT across all ages and sub-group analysis within the subgroup of cases aged 65 and older from 2016 onwards, a period when intensity-modulated radiotherapy (IMRT) was widely adopted. A total of 1,598 patients were included. Median OS since the first day of radiation therapy was 10.4 months (95% CI [9.6; 12.8]) for SCRT (n = 197) versus 16.2 months (95% CI [15.5; 16.9]) for LCRT (n = 1401) respectively. Subgroup analysis using stabilized inverse probability of treatment weighting (S-IPTW) showed indicating non-inferiority in elderly patients in median OS for elderly patients (≥ 65) with 10.6 months (95% CI [8.9; 14.0]) for SCRT (n = 147) versus 13.2 months (95% CI [8.9; 14.0]) for LCRT (n = 541). The median treatment cost of SCRT is about 6,000 USD lower, 25% less than LCRT. Compliance with the standard TMZ regimen post-radiation improved OS across all age groups. Considering comparable OS and shorter treatment duration, SCRT offers a viable, cost-effective option for elderly GBM patients. Adhering to standard TMZ also contributes to OS improvement. Further research reflecting key prognostic factors is essential to refining the role of SCRT.

Management of Locally Advanced Rectal Cancer: ASCO Guideline.

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual. ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines.Clinical Practice Guidelines and other guidance ("Guidance") provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by providers and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more.PURPOSETo provide evidence-based guidance for clinicians who treat patients with locally advanced rectal cancer.METHODSA systematic review of the literature published from 2013 to 2023 was conducted to identify relevant systematic reviews, phase II and III randomized controlled trials (RCTs), and observational studies where applicable.RESULTSTwelve RCTs, two systematic reviews, and one nonrandomized study met the inclusion criteria for this systematic review. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.RECOMMENDATIONSFollowing assessment with magnetic resonance imaging, for patients with microsatellite stable or proficient mismatch repair locally advanced rectal cancer, total neoadjuvant therapy (TNT; ie chemoradiation [CRT] and chemotherapy) should be offered as initial treatment for patients with tumors located in the lower rectum and/or patients who are at higher risk for local and/or distant metastases. Patients without higher-risk factors may discuss chemotherapy with selective CRT depending on extent of response, TNT, or neoadjuvant long-course CRT or short-course radiation. For patients who are candidates for TNT, the preferred timing for chemotherapy is after radiation, and neoadjuvant long-course CRT is preferred over short-course radiation therapy (RT), however short-course RT may also be a viable treatment option depending on circumstances. Nonoperative management may be discussed as an alternative to total mesorectal excision for patients who have a clinical complete response to neoadjuvant therapy. For patients whose tumors are microsatellite instability-high or mismatch repair deficient, immunotherapy is recommended.Additional information is available at http://www.asco.org/gastrointestinal-cancer-guidelines.

The impact of short-course total neoadjuvant therapy, long-course chemoradiotherapy, and upfront surgery on the technical difficulty of total mesorectal excision: an observational study with an intraoperative perspective.

Total neoadjuvant therapy (TNT) is becoming the standard of care for locally advanced rectal cancer. However, surgery is deferred for months after completion, which may lead to fibrosis and increased surgical difficulty. The aim of this study was to assess whether TNT (TNT-RAPIDO) is associated with increased difficulty of total mesorectal excision (TME) compared with long-course chemoradiotherapy (LCRT) and upfront surgery. Twelve laparoscopic videos of low anterior resection with TME for rectal cancer were prospectively collected from January 2020 to October 2021, with 4 videos in each arm. Seven colorectal surgeons assessed the videos independently, graded the difficulty of TME using a visual analog scale and attempted to identify which category the videos belonged to. The median age was 67 years, and 10 patients were male. The median interval to surgery from radiotherapy was 13 weeks in the LCRT group and 24 weeks in the TNT-RAPIDO group. There was no significant difference in the visual analog scale for difficulty in TME between the 3 groups (LCRT, 3.2; TNT-RAPIDO, 4.6; upfront, 4.1; P=0.12). A subgroup analysis showed similar difficulty between groups (LCRT 3.2 vs. TNT-RAPIDO 4.6, P=0.05; TNT-RAPIDO 4.6 vs. upfront 4.1, P=0.54). During video assessments, surgeons correctly identified the prior treatment modality in 42% of the cases. TNT-RAPIDO videos had the highest recognition rate (71%), significantly outperforming both LCRT (29%) and upfront surgery (25%, P=0.01). TNT does not appear to increase the surgical difficulty of TME.

Significant drop in serum C-reactive protein in patients with solid neoplasia and bacterial infection is associated with a better prognosis and identifies candidates for short-course antibiotic therapy

IntroductionThe greater predisposition to infections, as well as the possibility of a worse response to treatment, can lead to the excessive use of antimicrobials among cancer patients. C-reactive protein (CRP) has gained prominence as a tool for monitoring therapeutic responses and reducing the duration of antibiotic therapy; however, few studies have analyzed this protein in cancer patient populations. We hypothesize that cancer patients with a good response to antibiotic therapy show a faster decline in serum CRP levels, which would allow us to identify candidates for short-course treatments.ObjectiveTo evaluate the behavior of serum CRP levels among adult cancer patients using antibiotic therapy, and its association with the duration of this treatment, therapeutic response, and clinical recurrence.MethodsThis work consisted of a retrospective study with cancer patients admitted to a university hospital between September 2018 and December 2019. Adults (age ≥ 18 years) who underwent at least one course of antibiotic therapy were included. CRP behavior over the first 7 days of treatment was classified as: i) good response: when the CRP value on the fifth day of therapy reached 50% or less of the peak value detected in the first 48 h of treatment, and ii) poor response: Maintenance, within the same interval, of a CRP value > 50% of the peak value in the first 48 h. The duration of antibiotic therapy was categorized as up to seven full days or more. Outcomes were assessed by events that occurred during the 30 days of hospitalization or until hospital discharge. Primary outcome: Clinical recurrence of the index infection. Secondary outcomes: i) Death from any cause; ii) microbiological recurrence; iii) therapeutic response; iv) colitis associated with Clostridioides difficile; and v) isolation of multi-resistant bacteria, whether in clinical or surveillance samples.ResultsThe final analysis consisted of 212 patients, with a median age (IQ) of 59.2 (48 – 67) years old and a predominance of females (65%), who were hypertensive (35%), smokers (21%), and diabetics (17.8%). There was no difference in clinical recurrence between the two groups (8.1% vs. 12.2%; p = 0.364), with a lower 30-day mortality in the good CRP response group (32.2% vs. 14.5%; p = 0.002). Despite the tendency towards a lower occurrence of other secondary outcomes in the good response group, these differences were not statistically significant. In the poor CRP response group, outcomes like clinical recurrence, mortality, and therapeutic response were significantly worse, regardless of the duration of antibiotic treatment.ConclusionIn this study, cancer patients with a good CRP response during antibiotic therapy presented lower mortality and a higher proportion of satisfactory therapeutic responses. CRP can be a useful tool when combined with other clinical information in optimizing the duration of antimicrobial treatment in a hospitalized cancer population.

3HP preventive treatment among children and adolescents with HIV and child household contacts of TB patients

<sec><title>INTRODUCTION</title>India’s National TB Elimination Programme plans to roll out short-course TB preventive therapy (TPT) using 3 months of rifapentine and isoniazid (3HP). Understanding the feasibility and safety of children in programmatic settings is critical for widespread implementation. We present the findings of a targeted scale-up of 3HP among children and adolescents living with HIV (CALHIV) and child household contacts (>2 to <6 years) of pulmonary TB patients (CHHC).</sec><sec><title>METHODS</title>Between December 2021 and July 2023, eligible CALHIV and CHHC participants were given weekly dosages of 3HP for 3 months at antiretroviral therapy (ART) and TB clinics, respectively, of a public hospital in Pune, India.</sec><sec><title>RESULTS</title>Of 97 children screened, 91 initiated 3HP (32 CALHIV and 59 CHHC). The median age of CALHIV was 14 years; 66% were male and on dolutegravir-based ART. The median age of CHHC was 4 years; 47% were males. Thirty-one (97%) CALHIV and 56 (95%) CHHC completed 3HP without dolutegravir dose adjustment. None of the child participants discontinued 3HP due to adverse events. No child participant developed TB during 1 year of follow-up post-3HP.</sec><sec><title>CONCLUSION</title>Our study provides evidence of the uptake and feasibility of the planned nationwide rollout of 3HP.</sec>

Variation in Antibiotic Prescription in High-Risk Febrile Neutropenia in Portuguese Hospitals.

Febrile neutropenia (FN) is a potentially severe entity, particularly in hemato-oncologic patients who have higher incidence of colonization with multidrug-resistant bacteria. Discrepancies among guidelines contribute to divergence in antimicrobial practices. Our objective was to assess the variation of practices in antimicrobial therapy in high-risk FN among Portuguese hematologists. We conducted a cross-sectional study through the implementation of an online survey, open to all clinical hematologists in the country. To characterize practice patterns regarding critical elements in FN management, three clinical vignettes were designed to describe typical situations where narrow-spectrum empiric antibiotics (vignette 1), short-course therapy (vignette 2) and de-escalation (vignette 3) could be performed. The remaining questions characterized clinical experience, department size, and differentiation and decision-making process regarding FN antibiotic therapy. The survey yielded 31 responses from 11 hospitals across four regions. All respondents opted for empiric narrow-spectrum antibiotics, 22.6% opted for short-course therapy (mostly senior specialists from larger settings) and 35.5% for de-escalation (mostly young specialists). Availability of an FN protocol seemed to favor both approaches. These findings should be complemented by qualitative assessments of barriers to best practices and should support the need for interventions to improve antibiotic use in febrile neutropenia.

Factors Associated With the Discontinuation of Two Short-Course Tuberculosis Preventive Therapies in Programmatic Settings in the United States.

The objective of this study was to investigate timing and risk factors for discontinuation of short-course tuberculosis preventive therapy (TPT) comparing directly observed 3-month isoniazid/rifapentine (3HP) vs self-administered 4-month rifampin (4R). This was a subanalysis of a 6-month health department cohort (2016-2017) of 993 latent tuberculosis infection (LTBI) patients initiating 3HP (20%) or 4R (80%). Time at risk of TPT discontinuation was compared across regimens. Risk factors were assessed using mixed-effects Cox models. Short-course TPT discontinuation was higher with 4R (31% vs 14%; P < .0001), though discontinuation timing was similar. Latino ethnicity (hazard ratio [HR], 1.80; 95% CI, 1.20-2.90) and adverse events (HR, 4.30; 95% CI, 2.60-7.30) increased 3HP discontinuation risk. Social-behavioral factors such as substance misuse (HR, 12.00; 95% CI, 2.20-69.00) and congregate living (HR, 21.00; 95% CI, 1.20-360.00) increased 4R discontinuation risk. TPT discontinuation differed by regimen, with distinct risk factors. Addressing social determinants of health within TPT programs is critical to enhance completion rates and reduce TB disease risk in marginalized populations.

Cost-effectiveness of short-course radiotherapy versus long-course chemoradiation in organ preservation for locally advanced rectal cancer.

11089 Background: Short-course radiation therapy (SCRT) has previously been found to be cost-effective compared to long-course chemoradiation (LCRT) for patients with locally advanced rectal cancer undergoing operative management. However, non-operative management protocols have recently become a standard treatment option for patients diagnosed with locally advanced rectal cancer achieving a complete clinical response after total neoadjuvant therapy (TNT) as surgery has significant impacts on quality of life. Recent data suggests higher rates of local regrowth and a correspondingly lower rate of organ preservation with SCRT-TNT compared to LCRT-TNT. With this study, we evaluated the cost-effectiveness of SCRT versus LCRT in the setting of non-operative management for locally advanced rectal cancer. Methods: We built a microsimulation model to simulate 5-year outcomes for 1 million hypothetical patients aged 65 years with locally advanced rectal cancer treated with TNT including either SCRT or LCRT. Patients achieving a complete clinical response with TNT opted for a non-operative management approach, undergoing surgery only with subsequent local progression. Patients not achieving a complete clinical response went directly to surgery. The model incorporated costs, quality of life (measured by health utility), and probabilities of disease progression and death. We extracted probabilities of disease progression and death and health utilities from published literature. We assessed costs from the healthcare payer perspective. We measured cost-effectiveness with incremental cost-effectiveness ratio (ICER), with ICERs under $100,000 per quality-adjusted life-year (QALY) considered cost-effective. One way and probabilistic sensitivity analyses were used to test model uncertainty. Results: We found that compared to SCRT, LCRT increased overall cost by $10,457 and improved effectiveness by 0.16 QALYs resulting in an ICER of $67,200/QALY. The model was most sensitive to assumptions about risks of local recurrence in the non-operative setting, the health utility of non-operative management, and the costs of LCRT and SCRT. The model was not sensitive to assumptions about costs of diagnostic evaluation (i.e. flexible sigmoidoscopy) and probability of distant recurrence. Probabilistic sensitivity analysis demonstrated that LCRT was cost-effective in 91% of iterations. Conclusions: Long-course chemoradiation could represent a cost-effective strategy compared with short-course radiotherapy in the non-operative management of patients with locally advanced rectal cancer. The ongoing ACO/ARO/AIO-18.1 trial testing the hypothesis that LCRT-TNT will increase organ preservation rates relative to SCRT-TNT will help confirm these findings.

Tislelizumab plus tyrosine kinase inhibitor versus active surveillance in patients with ablated high-risk hepatocellular carcinoma: An open-label, parallel controlled, prospective cohort study.

e16238 Background: In IMbrave050, adjuvant atezolizumab plus bevacizumab demonstrated improvement in recurrence-free survival vs active surveillance in patients at high risk of hepatocellular carcinoma (HCC) recurrence following resection or ablation with curative intent. However, there is limited study on programmed cell death protein 1 (PD-1) inhibitor plus tyrosine kinase inhibitor (TKI) as postoperative adjuvant therapy for HCC. We aimed to assess the safety and efficacy of tislelizumab (a PD-1 inhibitor) plus TKI as adjuvant therapy versus active surveillance in patients at high risk of HCC recurrence after curative ablation. Methods: This study enrolled patients with HCC at high risk of recurrence following curative ablation. Patients were paralleled to Arm A (tislelizumab plus TKI) or Arm B (active surveillance). Patients in Arm A received tislelizumab (200 mg, IV, q3w) plus TKI for three months (4 cycles) following curative ablation, while those patients in Arm B underwent active surveillance. Primary endpoints were safety and tumor recurrence rate. Secondary endpoint was disease free survival (DFS). Exploratory endpoints included biomarkers related to the recurrence. Results: A total of 48 patients were enrolled with a median follow-up time of 283 days (IQR: 123-460 days, clinical cutoff date: 1 Jan 2024). Nine patients (37.5%) reported at least one adverse event of any degree in Arm A and three patients (12.5%) reported in arm B, most of which were mild. Only one patient in arm A experienced a grade 3 treatment-related adverse event, which improved after administration of symptomatic treatment. The recurrence rate of patients in arm A was 20.83%, which was significantly lower than the 58.3% in arm B (OR = 0.188 [95% CI: 0.052 - 0.674], P = 0.017). Four cycles of adjuvant tislelizumab plus TKI therapy was associated with significantly improved DFS (median, not evaluable [NE]) compared with active surveillance (median, 188 days [95% CI: 78.4 - 297.6 days]; HR = 0.396 [95% CI: 0161 - 0.973], P = 0.044). The absence of tislelizumab treatment (OR = 4.823 [95% CI: 1.091 - 21.329], P = 0.038) and multiple tumor lesions (OR = 7.651 [95% CI: 1.270 - 46.114], P = 0.026) were risk factors for recurrence of HCC after curative ablation. Conclusions: The safety of tislelizumab plus TKI combination therapy were generally manageable. Statistically significant and clinically meaningful improvement in tumor recurrence rate and DFS were seen in patients receiving combination therapy vs active surveillance. This study was a positive attempt to undergo short-course PD-1 inhibitor plus TKI combination therapy in patients with HCC at high risk of recurrence following curative ablation, showing promising efficacy in preventing HCC recurrence. Clinical trial information: NCT06059885 .

Immunoinhibitory effects of anti-tuberculosis therapy induce the host vulnerability to tuberculosis recurrence.

The host immune responses play a pivotal role in the establishment of long-term memory responses, which effectively aids in infection clearance. However, the prevailing anti-tuberculosis therapy, while aiming to combat tuberculosis (TB), also debilitates innate and adaptive immune components of the host. In this study, we explored how the front-line anti-TB drugs impact the host immune cells by modulating multiple signaling pathways and subsequently leading to disease relapse. Administration of these drugs led to a reduction in innate immune activation and also the cytokines required to trigger protective T cell responses. Moreover, these drugs led to activation-induced cell death in the mycobacterial-specific T cell leading to a reduced killing capacity. Furthermore, these drugs stalled the T cell differentiation into memory subsets by modulating the activation of STAT3, STAT4, FOXO1, and NFκB transcription factors and hampering the Th1 and Th17-mediated long-term host protective memory responses. These findings suggest the urgent need to augment directly observed treatment, short-course (DOTS) therapy with immunomodulatory agents to mitigate the adverse effects linked to the treatment.IMPORTANCEAs a central component of TB eradication initiatives, directly observed treatment, short-course (DOTS) therapy imparts immune-dampening effects during the course of treatment. This approach undermines the host immune system by delaying the activation process and lowering the immune response. In our investigation, we have unveiled the impact of DOTS on specific immune cell populations. Notably, the signaling pathways involving STAT3 and STAT4 critical for memory responses and NFκβ associated with pro-inflammation were substantially declined due to the therapy. Consequently, these drugs exhibit limited effectiveness in preventing recurrence of the disease. These observations highlight the imperative integration of immunomodulators to manage TB infection.

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61-69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1-10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688-1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4-82·5) in the no ADT group and 80·4% (76·6-83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population. Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60-69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0-10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612-0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6-75·7) in the short-course ADT group and 78·1% (74·2-81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.

3214: Preoperative short-course radiation therapy: data from clinical practice for protons and photons

3214: Preoperative short-course radiation therapy: data from clinical practice for protons and photons

Efficacy of Short-Course Antibiotic Therapy for Acute Cholangitis With Positive Blood Cultures: A Retrospective Study.

Short-term treatment of acute cholangitis is sufficient for cure compared with the standard treatment duration. Whether this short-course antimicrobial therapy is effective in patients with acute cholangitis with positive blood cultures has not been fully investigated. This study assessed whether patients with acute cholangitis could achieve successful outcomes with a three-day or shorter antimicrobial treatment period, even with a positive blood culture. This single-center retrospective study involved patients with acute cholangitis, defined according to the Tokyo Guidelines 2018 for any cause, who underwent successful biliary drainage and completed a seven-day or shorter antimicrobial treatment. Patients were categorized into six groups based on the duration of antibiotic use (short or standard) after endoscopic retrograde cholangiopancreatography and blood culture findings (positive, negative, or no collection). The primary outcome was the clinical cure rate, defined as no initial presenting symptoms by day 14 after biliary drainage and no recurrence or death by day 30. Secondary outcomes included a three-month recurrence rate and length of hospital stay. In total, 389 cases were selected, and 27 patients (6.9%) undergoing short-course therapy tested positive for blood culture. The clinical cure rate (n=25, 92.6%) in this group was comparable to that in the other groups. For the three-month recurrence rate (n=1, 3.7%) and median hospital stay (six days), this group's outcomes were either better or similar to those of the other groups. For cases of successful drainage in acute cholangitis, even with positive blood cultures, short-term antibiotic therapy may be appropriate.

Early Experience With Biologically Effective Dose-Comparable Short-Course Whole Brain Radiation Therapy for Metastatic Intracranial Disease.

For inpatients with metastatic intracranial disease burden exceeding established guidelines for stereotactic radiosurgery (SRS), the standard of care involves whole brain radiation therapy (WBRT), typically administered as a 2-week course of treatment with biologically effective dose (BED) of 60Gy. However, shorter course WBRT provides theoretical advantages in quality of life and decreasing systemic therapy delay. This retrospective study evaluates our early experience with BED-comparable short-course WBRT (23Gy in 5 fractions; BED=58.3Gy) for metastatic intracranial disease. Over a recent 2-month timeframe, 3 inpatients with intracranial disease burden exceeding SRS guidelines were administered BED-comparable short-course WBRT. Due to the high intracranial disease burden, 23Gy was chosen over 20Gy for 5-fraction WBRT due to the desire to optimally mimic the durability of the classic 30Gy in 10 fraction treatment regimen. The mean age at treatment was 65.7 years, the mean Karnofsky Performance Status (KPS) was 60, and the mean number of intracranial metastases was 20.3. The mean duration between inpatient Radiation Oncology consultation and the start of WBRT (following CT radiation therapy simulation) was 6.7 days. All patients completed WBRT no later than 2 weeks from the initial inpatient consultation. For inpatients with intracranial metastatic disease burden exceeding established SRS guidelines, BED-comparable short-course WBRT administered to 23Gy in 5 fractions (4.6Gy/fraction) is safe and efficacious. Given previous literature indicating that nearly half of the patients prescribed traditional 2-week WBRT die without completing treatment, BED-comparable WBRT represents an attractive and promising WBRT alternative in this patient population.

(103) - Prophylaxis of Donor-Derived HCV Infection in Cardiothoracic Transplant Recipients with Short-Course DAA Therapy

(103) - Prophylaxis of Donor-Derived HCV Infection in Cardiothoracic Transplant Recipients with Short-Course DAA Therapy

Shorter versus longer-course of antibiotic therapy for urinary tract infections in pediatric population: an updated meta-analysis.

Urinary tract infections (UTI) affect between 3% to 7.5% of the febrile pediatric population each year, being one of the most common bacterial infections in pediatrics. Nevertheless, there is no consensus in the medical literature regarding the duration of per oral (p.o.) antibiotic therapy for UTI among these patients. Therefore, our meta-analysis aims to assess the most effective therapy length in this scenario. PubMed, Cochrane, and Embase were searched for randomized controlled trials (RCTs) comparing short (≤ 5days) with long-course (≥ 7days) per os (p.o.) antibiotic therapy for children with UTI. Statistical analysis was performed using R Studio version 4.2.1, heterogeneity was assessed with I2 statistics, and the risk of bias was evaluated using the RoB-2 tool. Risk Ratios (RR) with p < 0.05 were considered statistically significant. Seventeen studies involving 1666 pediatric patients were included. Of these, 890 patients (53.4%) were randomized to receive short-course therapy. Patients undergoing short-course therapy showed higher treatment failure rates (RR 1.61; 95% CI 1.15-2.27; p = 0.006). Furthermore, there were no statistically significant differences between groups regarding reinfection (RR 0.73; 95% CI 0.47-1.13; p = 0156) and relapse rates (RR 1.47; 95% CI 0.8-2.71; p = 0.270). Conclusion: In summary, our results suggest that long-course p.o. antibiotic therapy is associated with a lower rate of treatment failure when compared to short-course p.o. antibiotic therapy. There was no statistical difference between both courses regarding reinfection and relapse rates within 15months. PROSPERO identifier: CRD42023456745. What is Known: • Urinary tract infections (UTIs) are common in children, affecting around 7.5% of those under 18. • The optimal duration of antibiotic treatment for pediatric UTIs has been a subject of debate. What is New: • Short-course therapy (5 or fewer days) was associated with a significantly higher failure rate when compared to long-course therapy. • There was no significant difference in reinfection and relapse rates within 15months between short and long-course therapy.