Benefits Of Therapy Research Articles

Roles of Parathyroid Hormone and Fibroblast Growth Factor 23 in Advanced Chronic Kidney Disease.

Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder. Levels of both hormones increase progressively in advanced CKD and can lead to damage in multiple organs. Secondary hyperparathyroidism (SHPT), characterized by parathyroid hyperplasia with increased PTH secretion, is associated with fractures and mortality. Emerging evidence suggests that these associations may be partially explained by PTH-induced browning of adipose tissue and increased energy expenditure. Observational studies suggest a survival benefit of PTHlowering therapy, and a recent study comparing parathyroidectomy and calcimimetics further suggests the importance of intensive PTH control. The mechanisms underlying the regulation of FGF23 secretion by osteocytes in response to phosphate load have been unclear, but recent experimental studies have identified glycerol-3-phosphate, a byproduct of glycolysis released by the kidney, as a key regulator of FGF23 production. Elevated FGF23 levels have been shown to be associated with mortality, and experimental data suggest off-target adverse effects of FGF23. However, the causal role of FGF23 in adverse outcomes in CKD patients remains to be established. Further studies are needed to determine whether intensive SHPT control improves clinical outcomes and whether treatment targeting FGF23 can improve patient outcomes.

Impact of High-Voltage Device Implantation in Elderly Japanese Patients With Heart Failure as Primary Prevention - Post Hoc Analysis of HINODE.

Despite an increased incidence of chronic heart failure (HF) and sudden cardiac death (SCD), the use of implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT) is much lower in Japan than in Western countries. The HF Indication and SCD Prevention Trial Japan (HINODE) prospectively assessed the mortality rate, appropriately treated ventricular arrhythmias (VA), and HF in Japanese patients with a higher risk of HF.Methods and Results: HINODE consisted of ICD, CRT-defibrillator (CRT-D), pacing, and non-device treatment cohorts. This subanalysis evaluated the impact of the implantation of high-voltage devices (HVD; ICD and CRT-D) in 171 Japanese patients. We compared all-cause mortality, VA, and HF events between elderly (age >70 years at study enrollment) and non-elderly HVD recipients. The estimated survival rate through 24 months in the HVD cohort was 85.8% (97.5% lower control limit 77.6%). The risk of all-cause mortality was increased for the elderly vs. non-elderly (hazard ratio [HR] 2.82; 95% confidence interval [CI] 1.01-7.91; P=0.039), but did not differ after excluding ICD patients with CRT-D indication (HR 2.32; 95% CI 0.79-6.78; P=0.11). There were no differences in VA and HF event-free rates between elderly and non-elderly HVD recipients (P=0.73 and P=0.55, respectively). Although elderly patients may have a higher risk of mortality in general, the benefit of HVD therapy in this group is comparable to that in non-elderly patients.

WITHDRAWAL: Quantitative modeling of approved and emerging therapeutics for modifying TTR levels in patients with Transthyretin Amyloid Cardiomyopathy.

Withdrawal: McGirr, K., Sarkar, S., Subramanian, K. (2023) "Quantitative modeling of approved and emerging therapeutics for modifying TTR levels in patients with Transthyretin Amyloid Cardiomyopathy" CPT: Pharmacometrics & Systems Pharmacology. https://doi.org/10.1002/psp4.13078. The above article, published online on November 6, 2023, in Wiley Online Library (http://wileyonlinelibrary.com), has been withdrawn by agreement between the authors, journal Editor-in-Chief, France Mentré, the American Society for Clinical Pharmacology and Therapeutics (ASCPT), and Wiley Periodicals LLC. The withdrawal has been agreed to at the authors' request due to a disagreement over the ownership of some data contained therein.

Long-term efficacy and safety of levonorgestrel releasing intrauterine system in the treatment of adenomyosis: evidence mapping.

To summarize evidence on levonorgestrel releasing intrauterine system (LNG-IUS) in the treatment of adenomyosis (AM) and to identify potential research gaps. Search was conducted in MEDLINE, The Cochrane Library, EMBASE, CBM, CNKI, and Wanfang. We included studies investigating patients with AM treated with LNG-IUS combined with conservative therapy. Thirty-nine studies compared LNG-IUS with other conservative therapeutic drugs. The most common comparison was GnRH-a+LNG-IUS vs. LNG-IUS alone, followed by LNG-IUS vs. mifepristone, expected treatment, and GnRH-a. GnRH-a+LNG-IUS was more beneficial in reducing the intensity of dysmenorrhea than LNG-IUS alone at the 6-month follow-up in patients with an enlarged uterus and moderate to severe dysmenorrhea. Large and well-designed studies are needed to confirm the efficacy of LNG-IUS and GnRH-a on reducing uterine volume at 6-month follow-up. Thirty-two studies investigated LNG-IUS as the postoperative management. The most common comparison was surgical excision+LNG-IUS vs. surgical excision. Results showed VAS scores were lower in the surgical excision+LNG-IUS group than in the surgical excision group at the 1-year follow-up. Evidence on endometrial thickness, quality of life, adverse events and beneficial effect at 3 and 5years are needed. Combined GnRH-a and LNG-IUS treatment was more efficacious than LNG-IUS alone for patients with an enlarged uterus and moderate to severe dysmenorrhea. Moreover, LNG-IUS seemed to show potential long-term benefits in postoperative therapy, warranting further meta-analysis for confirmation.

Antimicrobial Stewardship: A Correct Management to Reduce Sepsis in NICU Settings.

The discovery of antimicrobial drugs has led to a significant increase in survival from infections; however, they are very often prescribed and administered, even when their use is not necessary and appropriate. Newborns are particularly exposed to infections due to the poor effectiveness and the immaturity of their immune systems. For this reason, in Neonatal Intensive Care Units (NICUs), the use of antimicrobial drugs is often decisive and life-saving, and it must be started promptly to ensure its effectiveness in consideration of the possible rapid evolution of the infection towards sepsis. Nevertheless, the misuse of antibiotics in the neonatal period leads not only to an increase in the development and wide spreading of antimicrobial resistance (AMR) but it is also associated with various short-term (e.g., alterations of the microbiota) and long-term (e.g., increased risk of allergic disease and obesity) effects. It appears fundamental to use antibiotics only when strictly necessary; specific decision-making algorithms and electronic calculators can help limit the use of unnecessary antibiotic drugs. The aim of this narrative review is to summarize the right balance between the risks and benefits of antimicrobial therapy in NICUs; for this purpose, specific Antimicrobial Stewardship Programs (ASPs) in neonatal care and the creation of a specific antimicrobial stewardship team are requested.

Triazole antifungal drug interactions-practical considerations for excellent prescribing.

Systemic antifungal therapy is critical for reducing the mortality from many invasive and chronic fungal infections. Triazole antifungals are the most frequently prescribed antifungals but require attention to dosing and drug interactions. Nearly 600 severe drug-drug interactions and over 1100 moderate interactions requiring dose modifications are described or anticipated with systemic antifungal agents (see https://www.aspergillus.org.uk/antifungal-drug-interactions/). In this article, we address the common and less common, but serious, drug interactions observed in clinical practice with triazole antifungals, including a group of drugs that cannot be prescribed with all or most triazole antifungals (ivabradine, ranolazine, eplerenone, fentanyl, apomorphine, quetiapine, bedaquiline, rifampicin, rifabutin, sirolimus, phenytoin and carbamazepine). We highlight interactions with drugs used in children and new agents introduced for the treatment of haematological malignancies or graft versus host disease (midostaurin, ibrutinib, ruxolitinib and venetoclax). We also summarize the multiple interactions between oral and inhaled corticosteroids and triazole antifungals, and the strategies needed to optimize the therapeutic benefits of triazole antifungal therapy while minimizing potential harm to patients.

Radiation Oncologists' Perspectives on Oligometastatic Prostate Cancer: A Survey from Korean Oligometastasis Working Group.

Interest in the oligometastatic prostate cancer (OMPC) is increasing, and various clinical studies have reported the benefits of metastasis-directed radiation therapy (MDRT) in OMPC. However, the recognition regarding the adopted definitions, methodologies of assessment, and therapeutic approaches is diverse among radiation oncologists. This study aims to evaluate the level of agreement for issues in OMPC among radiation oncologists. We generated 15 key questions (KQs) for OMPC relevant to definition, diagnosis, local therapies, and endpoints. Additionally, three clinical scenarios representing synchronous metastatic prostate cancer (mPC) (case 1), metachronous mPC with visceral metastasis (case 2), and metachronous mPC with castration-resistance and history of polymetastasis (case 3) were developed. The 15 KQs were adapted according to each scenario and transformed into 23 questions with 6-9 per scenario. The survey was distributed to 80 radiation oncologists throughout the Republic of Korea. Answer options with 0.0-29.9%, 30-49.9%, 50-69.9%, 70-79.9%, 80-89.9%, and 90-100% agreements were considered as no, minimal, weak, moderate, strong, and near perfect agreement, respectively. Forty-five candidates voluntarily participated in this study. Among 23 questions, near perfect (n = 4), strong (n = 3), or moderate (n = 2) agreements were shown in nine. For the case recognized as OMPC with agreements of 93% (case 1), near perfect agreements on the application of definitive radiation therapy (RT) for whole metastatic lesions were achieved. While ≥70% agreements regarding optimal dose-fractionation for metastasis-directed RT (MDRT) has not been achieved, stereotactic body RT (SBRT) is favored by clinicians with higher clinical volume. For the case recognized as OMPC, near perfect agreement for the application of definitive RT for whole metastatic lesions was reached. SBRT was more favored as a MDRT by clinicians with a higher clinical volume.

Psoriatic arthritis - Tofacitinib as a new treatment

Introduction: JAK inhibitors are used in the treatment of psoriatic arthritis when there is a lack of effective response or intolerance to first-line drugs or their use must be discontinued due to the presence of side effects. JAK inhibitors inhibit the JAK-STAT signaling pathway which plays a significant role in the pathogenesis of many inflammatory and autoimmune diseases. This mechanism leads to a reduction in the level of pro-inflammatory cytokines which causes rapid improvement in the patient's clinical condition. Tofacitinib is the best-known drug in this group; its use carries an increased risk of cardiovascular events and reactivation of the varicella-zoster virus. Regular monitoring of patients results in faster detection of the first signs of undesirable effects and the cessation of their progression. The drug's safety profile is acceptable and the benefits outweigh possible complications. Aim of the study: The aim of the study is to summarize the available knowledge about tofacitinib treatment in psoriatic arthritis. The way of work, effectiveness of treatment and potential side effects were summarized and described. Materials and methods: The literature available in PubMed database was reviewed using the following keywords: “Psoriatic arthritis”, “Tofacitinib”, “JAK inhibitors”, “JAK-STAT” Conclusion: Tofacitinib treatment in rheumatology is used in psoriatic arthritis. The rapid improvement in the clinical condition of patients treated with JAK inhibitors is due to their direct impact on the modulation of the pathogenesis of the disease. The predictable benefits of therapy outweigh the side effects which can be detected at an early stage with regular monitoring of the patient.

Steroid therapy in acute exacerbation of fibrotic interstitial lung disease.

Evidence for the benefit of steroid therapy in acute exacerbations (AEs) of idiopathic pulmonary fibrosis (IPF) is limited; however, they remain a cornerstone of management in other fibrotic interstitial lung diseases. This retrospective observational study assesses the effect of steroid treatment on in-hospital mortality in patients with acute exacerbation of fibrotic interstitial lung disease (AE-FILD) including IPF and non-IPF ILDs. AE-FILD cases over a 10-year period were filtered using a code-based algorithm followed by individual case evaluation. Binary logistic regression analysis was used to assess the relationship between corticosteroid treatment (defined as ≥0.5 mg/kg/day of prednisolone-equivalent for ≥3 days within the first 72 h of admission) and in-hospital mortality or need for lung transplantation. Secondary outcomes included readmission, overall survival, requirement for domiciliary oxygen and rehabilitation. Across two centres a total of 107 AE-FILD subjects were included, of which 46 patients (43%) received acute steroid treatment. The steroid cohort was of younger age with fewer comorbidities but had higher oxygen requirements. Pre-admission FVC and DLCO, distribution of diagnoses and smoking history were similar. The mean steroid treatment dose was 4.59 mg/kg/day. Steroid use appeared to be associated with increased risk of inpatient mortality or transplantation (OR 4.11; 95% CI 1.00-16.83; p = 0.049). In the steroid group, there appeared to be a reduced risk of all-cause mortality in non-IPF patients (HR 0.21; 95% CI 0.04-0.96; p = 0.04) compared to their IPF counterparts. Median survival was reduced in the steroid group (221 vs. 520.5 days) with increased risk of all-cause mortality (HR 3.25; 95% CI 1.56-6.77; p < 0.01). In this two-centre retrospective study of 107 patients, AE-FILD demonstrates a high risk of mortality, at a level similar to that seen for AE-IPF, despite steroid treatment. Clinicians should consider other precipitating factors for exacerbations and use steroids judiciously. Further prospective trials are needed to determine the role of corticosteroids in AE-FILD.

The psychotherapeutic use of dance as an educational tool to improve social skills in children with autism

ABSTRACT Educational tools based on the use of dance for professionals working with children with autism spectrum disorders (ASD) are scarce. The aim of this article is to highlight the benefits of dance therapy by presenting new research in the literature, and to describe the results of an intervention proposal that includes dance therapy in this field of education. The relevance of arts education as a strategy of attention to diversity in schools for the integrated development of academic and social skills is highlighted. The intervention proposal was designed with a programme of activities that included dance therapy and was implemented in children with autism. The aim was to determine whether it contributed to the development of their social skills. A descriptive qualitative methodology was used, with a purposive sampling of subjects affected by autism spectrum disorder attending the same educational centre. The results were collected in a field diary detailing the evolution of each subject in each module. Stufflebeam’s CIPP model was used to evaluate the results in terms of improvements in social skills. The results confirmed that dance therapy is an appropriate tool for the development of social skills in students with ASD.

Unveiling the influence of SGLT2 inhibitors on clinical outcomes in patients with cancer with therapy-related cardiac dysfunction: A meta-analysis and systemic review.

e24003 Background: Cancer patients undergoing chemotherapy suffer from a variable degree of cancer therapy–related cardiac dysfunction and heart failure (HF). It is known that sodium glucose co-transporter 2 (SGLT2) inhibitors improve outcomes in patients with HF independent of diabetes mellitus and left ventricular ejection fraction; our study aims to investigate the potential benefits of SGLT2 inhibitory therapy specifically in cancer patients undergoing chemotherapy. Methods: We performed an electronic search on PubMed, Embase, and Cochrane, from the inception of databases till January 29, 2024, to identify all the articles that compared the use of SGLT2 inhibitors in adult (≥18 years) with type 2 diabetes mellitus and exposure to cardiotoxic antineoplastic therapy, subsequently diagnosed with cardiomyopathy, heart failure, or LVEF &lt; 40%. The data was extracted and pooled using a random effects model to calculate the odds ratio (OR) with a respective 95% confidence interval (CI). R software (v.4.3) was used for all statistical analyses. Results: Our search identified three observational studies with a total of 3,164 patients (SGLT2- inhibitor group: 1,550; Control group: 1,614). We found that the use of SGLT2 inhibitors was associated with a lower risk of all-cause mortality (OR: 0.25 [0.20, 0.31]; I2 = 16%; p &lt; 0.001), hospitalizations from heart failure (OR: 0.25 [0.10, 0.62]; I2 = 0%; p = 0.003), and acute exacerbation of heart failure (OR: 0.35 [0.27, 0.47]; I2 = 0%; p &lt; 0.001). Conclusions: Our findings suggest a favorable association between the use of SGLT2 inhibitors and reduced mortality, as well as improved cardiac clinical outcomes in cancer patients undergoing chemotherapy. However, further validation through large-scale studies and randomized controlled trials across diverse malignancies is warranted to establish the efficacy of these drugs. [Table: see text]

Use of immunotherapy with check point inhibitors in soft tissue sarcoma: Analysis from single institution.

e23566 Background: Traditional treatments for soft tissue sarcomas include surgery, chemotherapy, and radiation. Effectiveness of Check point inhibitors for sarcoma has been unsatisfactory thus far. Major clinical trials PEMBROSARC and SARC028 revealed median PFS of 2 and 4.5 months, respectively. The FDA has approved three immunotherapy (IO) therapies for sarcoma. Atezolizumab was approved for alveolar soft part sarcoma. Dostarlimab is approved for sarcoma with DNA mismatch repair deficiency (dMMR), Sarcoma patients with high microsatellite instability (MSI-H), dMMR, or tumor mutational burden can receive pembrolizumab. A single-institution analysis of soft tissue sarcoma patients with IO is presented in this paper. Methods: All soft tissue sarcoma patients who have received IO from January 2021 to now have been included. At our institute, a total of seven patients received IO for soft tissue sarcoma. Observations were made regarding their fundamental characteristics and the progression free survival (PFS). The data was not statistically examined due to the small sample size and the heterogeneity of the data. Results: 2 of 7 trial patients were lost to follow-up. Recurrent autoimmune hepatitis terminated IO for another patient. Most of the patients are elderly with the median age of 78. Given their comorbidities and age, IO was chosen as the first line for 5 patients. Median PFS was 5.8 months. High PDL1 ( &gt; / = 5%) patients had a median PFS of 5.6 months, while low PDL1 patients had 4.5 months. However, one patient with low PDL1 had PFS of 7 months. 5/7 patients didn’t have IO related side effects. Two patients developed Autoimmune (AI) hepatitis. Conclusions: The limited sample size prevented definitive conclusions from being drawn. Despite the unsatisfactory outcomes, it is worth mentioning that IO provided a certain degree of PFS in older patients with comorbidities who are not suitable candidates for chemotherapy. Based on limited data, patients with high PDL1 status appear to benefit more. IO alone has not shown promising results. In clinical trials, IO is being tested with chemotherapy and Tyrosine kinase inhibitors. The findings from these trials will provide valuable insights into the potential benefits of combination therapy. [Table: see text]

Why and How to Integrate Early Palliative Care Into Cutting-Edge Personalized Cancer Care.

Early palliative care, palliative care integrated with oncology care early in the course of illness, has myriad benefits for patients and their caregivers, including improved quality of life, reduced physical and psychological symptom burden, enhanced prognostic awareness, and reduced health care utilization at the end of life. Although ASCO and others recommend early palliative care for all patients with advanced cancer, widespread implementation of early palliative care has not been realized because of barriers such as insufficient reimbursement and a palliative care workforce shortage. Investigators have recently tested several implementation strategies to overcome these barriers, including triggers for palliative care consultations, telehealth delivery, navigator-delivered interventions, and primary palliative care interventions. More research is needed to identify mechanisms to distribute palliative care optimally and equitably. Simultaneously, the transformation of the oncology treatment landscape has led to shifts in the supportive care needs of patients and caregivers, who may experience longer, uncertain trajectories of cancer. Now, palliative care also plays a clear role in the care of patients with hematologic malignancies and may be beneficial for patients undergoing phase I clinical trials and their caregivers. Further research and clinical guidance regarding how to balance the risks and benefits of opioid therapy and safely manage cancer-related pain across this wide range of settings are urgently needed. The strengths of early palliative care in supporting patients' and caregivers' coping and centering decisions on their goals and values remain valuable in the care of patients receiving cutting-edge personalized cancer care.

Assessing the landscape of integrative oncology at US comprehensive cancer centers (CCC).

e13565 Background: Interest in integrative oncology (IO) has grown among patients and its availability has expanded within CCCs. This study assesses the availability of IO programs in U.S. CCCs. Methods: In 2023, a cross-sectional survey was sent to CCCs including NCI-designated CCCs by email regarding IO programs. Participants were asked to describe the importance of IO within their cancer center, the programs and services offered, and how the programs are provided. Results: Of ninety-four survey invitations sent, fifty-eight completed surveys were returned (response rate 62%). Three-fourths of completed surveys (74%) came from NCI-designated CCCs. Over half of respondents (57%) rated IO services to be important (or very important) at their center with 53% stating that their center has a formal IO clinical program. Univariate analysis showed that non-NCI centers were more likely to perceive IO services as being important compared to NCI-designated centers (100% vs. 77%, p=0.04). Respondents stated that their IO program has been in existence for ≥10 years (40%), 5-9 years (26%), and 0-4 years (34%). Among the surveyed cancer centers, availability of IO program was 33% (adult and pediatric) vs. 49% (adult only). The IO programs are available to patients with active cancer (91%), patients in survivorship off-treatment (81%), and healthy patients without a history of cancer (22%). The IO services were offered in an outpatient clinic on the main campus (76%), community sites (29%), or inpatient settings (40%). The most common oncology specific services reported were nutrition (51%), exercise counseling (42%), mind-body medicine (38%), and acupuncture (33%). The clinicians who provided integrative medicine consultations were primarily in internal medicine (31%), family medicine (26%), and medical oncology (19%). In inpatient and outpatient settings, insurance was billed for physical therapy (50% vs. 67%) and diet/nutrition (36% vs. 50%) services, whereas acupuncture (47%) and massage (43%) services were charged by cash/card in an outpatient setting only. Music therapy (33% vs. 47%) and pet therapy (34% vs. 43%) services were offered for free most commonly in both inpatient and outpatient settings, respectively. The highest average out of pocket fee service was acupuncture ($42±27) followed by integrative medicine consultations ($34±29). Conclusions: Despite increasing patient interest and established benefits of integrative therapies as noted by recently published ASCO clinical guidelines, only half of CCCs reported having a formal IO program. More research is needed to understand the gap between patient interest, the growing evidence-base, and how to expand integrative oncology services within existing cancer centers.

Real world outcomes of sequential ADC therapy in metastatic breast cancer: Patients treated with sacituzumab govitecan and trastuzumab deruxtecan.

1085 Background: Sacituzumab govitecan (SG) and trastuzumab deruxtecan (TDXd) are antibody drug conjugates (ADCs) that are approved for the treatment of HER2 low metastatic breast cancer (MBC). Both carry payloads which inhibit topoisomerase 1, and it is unknown whether these ADCs retain clinical activity when used sequentially to each other. Here we present a retrospective study of patients treated with both SG and TDXd at our institution and report real world progression free survival (PFS), clinical factors associated with longer PFS, and whether ADC sequence impacts outcome. Methods: All patients with MBC treated at MSKCC who had received both SG and TDXd (in any order) were eligible for inclusion. Clinicopathological and demographic data were obtained from retrospective chart review. PFS was determined clinically and calculated using Kaplan-Meier survival analysis. Univariate and multivariate associations of survival were assessed using Cox proportional hazards models. Results: Eighty-five patients met eligibility per the criteria above: 54 with estrogen receptor positive (ER+) MBC and 31 with triple negative breast cancer (TNBC). 33 patients received SG followed by TDXd (14 ER+, 19 TNBC), and 52 received TDXd followed by SG (40 ER+, 12 TNBC). Median age at time of second ADC treatment (ADC2) was 59 among all patients, 62 among SG first, and 58 among TDXd first. This cohort was heavily pre-treated, with median 5 prior therapies at the time of first ADC (ADC1) and 7 at the time of ADC2. Both the SG first and TDXd first cohorts had median 1 line of intervening therapy between ADCs. In the SG first group, median ADC2 (TDXd) PFS was 3.5 months (95%CI 2.7-7.7), and in the TDXd first group median ADC2 (SG) was 2.8 months (95%CI 2.6-3.7). On multivariate analysis, neither ADC sequence (SG first vs. TDXd first, HR 1.30, 95%CI 0.71-2.37, p=0.4) nor ER status (TNBC vs. ER+, HR 1.21, 95%CI 0.63-2.32, p=0.6) showed statistically significant differences in ADC2 PFS between these groups. Instead, later treatment line at the time of ADC2 was significantly associated with shorter ADC2 PFS (continuous, HR 1.11, 95%CI 1.01-1.23, p=0.03). To separately evaluate differences in PFS for each ADC depending upon whether it was first or follow-up therapy, median ADC1 vs. ADC2 PFS is summarized by ADC (Table). Conclusions: In this heavily pre-treated patient cohort, the clinical activity of both SG and TDXd appear modest in the ADC2 setting. Further studies are needed to confirm these findings and to determine whether payload cross-resistance may undermine the benefit of sequential ADC therapy. [Table: see text]

Correlation of serum anti-Müllerian hormone (AMH) levels on identification of premenopausal patients (pts) with hormone receptor positive (HR+), HER2-negative, node-positive breast cancer most likely to benefit from adjuvant chemotherapy in SWOG S1007 (RxPONDER).

505 Background: SWOG S1007 was a phase 3 randomized trial to evaluate the benefit of endocrine therapy alone (ET) or with chemotherapy (CET) in pts with HR+/HER2- invasive breast cancer with recurrence score (RS) ≤ 25. There was no invasive disease-free survival (IDFS) benefit for CET compared to ET in postmenopausal women However, in premenopausal women CET had an IDFS improvement compared to ET (HR=0.60; 95% 0.43-0.83). The objective was to further refine patient subgroups who benefit from CET, we measured baseline hormone levels in S1007 pts to quantify their menstrual status by serum hormone levels and associated clinical outcomes. Methods: Serum estradiol (E), progesterone (P), follicular stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), and inhibin B (IB) were assessed on baseline serum samples from 1,015 pts who self-reported being premenopausal and age &lt; 55. Magnetic fluorescent bead-based immunoassays ( i.e., Luminex assays) or colorimetric ELISAs were performed at the Biomarker Discovery Laboratory at the University of Kansas Medical Center to measure hormone levels. Associations of the markers (both continuous and dichotomized) with IDFS and distant relapse-free survival (DRFS) were tested for prognosis and prediction of CET benefit using Cox regression. Results: Single baseline measurement of IB, P, E, LH, FSH, or combination of E/LH/FSH, was not prognostic for IDFS or predictive for chemotherapy benefit. However, AMH levels (≥10 pg/mL) showed significant interaction with chemotherapy benefit (p=0.019), and risk increased with continuous AMH with ET alone, but not CET (p=0.03). Compared to ET alone, CET was beneficial in the 79% of premenopausal patients with AMH levels ≥10 pg/mL, a standard cutoff to define normal ovarian reserve (HR=0.48; 95% 0.33-0.69, adjusting for RS). CET was not beneficial in the 21% with AMH &lt; 10 (HR=1.21; 95% 0.60-2.43). Absolute 5-year IDFS benefit of CET for RS ≤ 25 was 7.8% (95.2%-87.4%) for AMH ≥ 10 vs. -1.7% (89.1%-90.8%) for AMH &lt; 10. DRFS showed a similar pattern with CET benefit in AMH ≥10 pg/mL (5-year DRFS benefit: 4.4%; HR=0.41; 95% 0.25-0.68, adjusting for RS) and no benefit in AMH &lt; 10 (5-year DRFS benefit: -0.9%, HR=1.50; 95% 0.62-3.63). Conclusions: Among self-reported premenopausal patients &lt; age 55, pts with baseline serum AMH levels ≥10 pg/mL showed significant benefit from CET compared to patients with AMH levels &lt;10 pg/mL. AMH levels were a better indicator of CET benefit than self-reported menopause status, age, or E/LH/FSH levels. Use of AMH-based selection of patients may inform who most benefits from the addition of adjuvant chemotherapy to ET. Clinical trial information: NCT01272037 .

Multi-institutional study of reirradiation for recurrent high grade glioma.

2063 Background: Treatment options are limited for recurrent WHO Grade 3-4 glioma (HGG). Reirradiation (ReRT) is an option, but the ideal treatment regimen and the benefit of concurrent and adjuvant systemic therapy in the recurrent setting remains unclear. Methods: A retrospective review of patients with recurrent HGG treated with reRT was conducted at 12 institutions. Eligible patients were treated with two courses of fractionated RT (&gt;3 fractions) for glioma with the second course being for HGG. To estimate overall and progression free survival times, the Kaplan-Meier method was used. To assess the relationship between survival times and study variables, Cox proportional hazard regression models were used to calculate hazard ratios and the corresponding 95% confidence interval along with the p-value. SAS (version 9.4, Cary, NC, USA) was used for all analyses. P values &lt; 0.05 were assumed to be statistically significant. Results: 482 eligible patients were identified from 1997 to 2023. 235 (54%) had histologic confirmation of glioblastoma at reRT. The median age at reRT was 53.1 years and median KPS was 80. 196 patients (51%) were treated with reRT at their initial recurrence and 122 (30%) had an IDH mutation. The most common reRT dose and number of fractions were 35 Gy and 10 fractions. 192 patients (44%) and 95 (24%) received concurrent (conc) and adjuvant (adj) temozolomide (TMZ) respectively and 116 (27%) and 110 (28%) received conc and adj bevacizumab (BEV) respectively with reRT. Median OS and PFS were 9.8 and 5.3 months. OS (16.6 vs 7.8 months, HR 2.44 p &lt; 0.01) and PFS (8.6 vs 4.6 months, HR 1.85 p &lt; 0.01) were longer in patients with IDH mutations. Receipt of conc and adj TMZ with reRT was associated with improved OS (HR 0.67 p &lt; 0.01 and HR 0.49 p &lt; 0.01 respectively) and PFS (HR 0.66 p &lt;0.01 and HR 0.47 p &lt; 0.01 respectively). Receipt of concBEV with reRT was associated with worse OS (HR 1.66 p &lt; 0.01) but not PFS (HR 1.15 p = 0.28). AdjBEV was not associated with OS or PFS. Concurrent and adjTMZ were associated with improved OS ( p = 0.04 and &lt;0.01) and PFS ( p = 0.01 and &lt;0.01) for IDHwt tumors. In IDHmt tumors, concTMZ was associated with improved OS but not PFS ( p = 0.03 and 0.11), while adjTMZ was associated with improved OS and PFS ( p = 0.05 and &lt;0.01). Symptomatic adverse radiation effects and Grade 3 or greater neurologic toxicity were seen in 107 (25%) and 86 (20%) of patients respectively. Neither conc nor adjBEV nor TMZ were associated with symptomatic ARE. ConcBEV was associated with lower (13% vs 23%, p = 0.03) and concTMZ was associated with higher rates (25% vs 15%, p = 0.01) of Grade 3 or greater neurologic toxicity. Conclusions: The use of concurrent and adjuvant TMZ with reRT are associated with improved OS and PFS in recurrent HGG. OS and PFS are improved with conc and adjTMZ for IDHwt tumors, while there was no PFS benefit to concTMZ in IDHmt tumors. The rate of high grade neurologic toxicity was decreased with the use of concurrent BEV and increased with the use of concTMZ.

Breast Cancer Index re-stratifies 21-gene assay risk groups for late distant recurrence and extended endocrine therapy benefit: Results from the BCI Registry Study.

529 Background: Patients with hormone receptor-positive (HR+) breast cancer face a prolonged risk for late distant recurrence (DR), even after 5 years of adjuvant endocrine therapy. The BCI (Breast Cancer Index, Biotheranostics) is a genomic assay that provides the risk of late DR and predicts the likelihood of benefit from extended endocrine therapy (EET) based on the H/I (HOXB13/IL-17BR) ratio. The 21-gene RS (Recurrence Score; Oncotype DX, Exact Biosciences) test provides the 9-year risk of DR and the benefit from adjuvant chemotherapy (CT) in HR+/HER2− breast cancer. However, the RxPONDER trial showed that RS was not predictive of CT benefit in premenopausal women with N1 disease. Here, we investigated the concordance between BCI prognostic score and H/I versus RS in HR+/HER2- patients from the BCI Registry study. Methods: The BCI Registry study is a prospective, multi-institutional study to evaluate the long-term clinical outcome, decision impact and medication adherence in early-stage HR+ breast cancer patients. Based on TAILORx and RxPONDER results, RS stratified patients into four risk groups: Age ≤ 50, No CT benefit (RS ≤ 15); Age ≤ 50, CT benefit (RS&gt;15); Age &gt; 50, No CT benefit (RS ≤ 25); and Age &gt; 50, CT benefit (RS &gt; 25). Kendall’s correlation coefficient (R) was used to estimate the correlation between BCI prognostic score, BCI (H/I) and RS as continuous variables. Results: BCI and RS results were reported for 847 patients (76% T1; 59% grade II; 85% N0). H/I classified 559 patients (66%) as H/I-Low and 288 (34%) as H/I-High, respectively, while BCI prognostic risk scores classified 434 patients (51%) as low-risk and 413 (49%) as high-risk for late DR. RS classified 30 patients (4%) as Age ≤ 50, No CT benefit, 38 (5%) as Age ≤ 50, CT benefit, 665 (78%) as Age &gt; 50, No CT benefit and 114 (13%) as Age &gt; 50, CT benefit. When analyzed as continuous variables, BCI H/I and prognostic score showed a weak correlation with RS with R=0.18 and R=0.2, respectively. Based on categorical groups, H/I had low concordance with RS for younger women (Age ≤ 50) but showed some correlation with RS for older women (Age &gt; 50). Among those older than Age 50, H/I identified 31% of those with no CT benefit as likely to benefit from EET while 39% of those with CT benefit as not likely to benefit from EET. Conclusions: BCI H/I and prognostic risk scores exhibited low concordance with RS risk categories. H/I consistently re-stratified RS risk categories into distinct H/I-Low and -High groups, further substantiating that prediction of CT benefit does not equate to prediction of EET benefit. [Table: see text]

Incidence des infections urinaires post-cystomanométrie chez les patients présentant une vessie neurogène – évaluation des pratiques

ObjectiveThe indication for prophylactic antibiotic therapy during cystomanometry to prevent urinary tract infection (UTI) has long been recommended. However, limited data support this approach. Our study aims to evaluate the incidence of UTIs following cystomanometry without prophylactic antibiotics in patients with neurogenic bladder. Materials and methodsThis prospective, monocentric study was conducted from February 2023 to March 2023 at a specialized neuro-urology center, including all consecutive patients with lower urinary tract disorders of neurogenic origin referred for cystomanometry. The occurrence of UTIs following cystomanometry was assessed via telephone follow-up on day 14. ResultsA total of 100 patients were included, with a median age of 51years, with neurogenic bladder predominantly attributed to spinal cord injury (69/100). Ultimately, 11 patients reported UTIs within 14days post-cystomanometry, with only one being febrile, and none requiring hospitalization. No specific risk factors could be identified. ConclusionAccording to our study, the incidence of UTIs following cystomanometry without prophylactic antibiotic therapy is 11%, which is equivalent to the incidence with antibiotic prophylaxis. These preliminary results support the lack of benefit of peri-cystomanometry antibiotic therapy.

MetALD: Does it require a different therapeutic option?

New guidelines for the definitions of steatotic liver disease have named the entity of MetALD as an overlap condition of metabolic-dysfunction associated steatotic liver disease (MASLD) and alcohol-related liver disease. There is a broad range of therapeutics in all stages of development for MASLD but these therapeutics in general have not been studied in patients with significant ongoing alcohol use. In this review we discuss the current understanding of the endogenous and exogenous risks for MASLD and MetALD. Rational strategies for therapeutic intervention in MetALD include biopsychosocial interventions, alcohol use cessation strategies including the use of medications for alcohol use disorder and judicious use of therapeutics for steatotic liver disease. Therapeutics with promise for MetALD include incretin-based therapies, fibroblast growth factor 21 (FGF21) agonists, thyroid hormone receptor beta (THR- β) agonists, sodium-glucose co-transporter 2 (SGLT2) inhibitors and agents to modify de-novo lipogenesis (DNL). Currently glucagon like peptide 1 receptor agonists (GLP-1ra) and peroxisome proliferator-activated receptor (PPAR) γ agonists have the largest body of literature supporting their use in MASLD and there is a paucity of agents in trials for alcohol-related liver disease. From existing studies, it is not clear if unique therapeutics or a combinatorial approach are needed for MetALD. Further elucidation of the safety and benefits of MASLD-related therapies are of paramount importance for advancing therapeutics for MetALD in carefully designed inclusive clinical trials.