Median Cumulative Dose Research Articles

Rituximab Administration to Treat Nephrotic Syndrome in Children: 2-Year Follow-Up.

Steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) significantly affect children's quality of life. There are frequent relapses in SSNS and progression in SRNS. IPNA guidelines suggest that monoclonal antibodies like rituximab (RTX) are promising treatments. This study aims to evaluate the long-term efficacy and safety of rituximab administration in children with SSNS, encompassing FRNS and SDNS, and SRNS over a two-year follow-up period, facilitating individualized management. We conducted an open-label, multicenter, randomized, and patient-oriented study (RICHNESS), involving children aged 3-18 with SRNS (18) and SSNS (11) undergoing 2 years continuous RTX therapy. The primary outcome was complete/partial remission (CR/PR), as defined by IPNA/KDIGO guidelines, at 6, 12, 18, and 24 months on RTX; secondary outcomes included adverse events. Key endpoints included the estimated glomerular filtration rate (eGFR), the albumin-to-creatinine ratio (ACR), CD20 levels, IgG levels, and the incidence of infections. Kidney biopsies were performed in 94% of SRNS patients. RTX was administered every 6-9 months, depending on CD20 levels, IgG levels, and the presence of infections. The eGFR and ACR were assessed every 6 months. Some 31 children were selected for RTX treatment. Overall, 2 experienced severe allergic reactions, leading to their exclusion from the final analysis of 29 children. In the SSNS group, all children achieved and maintained complete remission within 2 years. Remission rates in the SRNS group ranged from 39% (RR 0.78; 95% CI: 16.4-61.4%, NNT 9) at the 6th month to 72% (RR 1.44; 95% CI: 51.5-92.9%) over the 2-year follow-up period due to continuous RTX therapy. The median duration of RTX use was 26.1 months, with a median cumulative dose of 1820 mg/m2. Adverse reactions and complications were presented by mild infusion-related reactions in 3 children (10.3%), severe allergic reactions in 2 children (6.2%), hypogammaglobulinemia in 7 children (24%), infections in 3 children (10.3%), severe destructive pneumonia in 1 child, recurrent respiratory infections in 2 children, and neutropenia in 1 child (3.44%). RTX was tolerated well, and proved highly effective as a steroid-sparing agent, offering potential in terms of stopping relapses and minimizing steroid-related side effects. It also demonstrated efficacy in slowing progression in SRNS, indicating potential for use in ACR reduction and renal function restoration, but requires careful use given potential severe allergic reactions and infectious complications. Further studies should focus on long-term cost-effectiveness and deferred side effects.

RADT-17. FRACTIONATED REIRRADIATION OF RECURRENT IDH WILDTYPE GLIOBLASTOMA: HIGHER REIRRADIAITON DOSE AND SAFETY

Abstract The optimal regimen, normal tissue tolerances, and appropriate indications for reirradiation for recurrent glioblastoma (GBM) are uncertain. We evaluate outcomes and toxicity after fractionated reirradiation. Patients with recurrent IDH wildtype GBM after prior standard radiotherapy during 2007-2022 were retrospectively reviewed. All patients initially received conventionally fractionated radiotherapy. Radiation necrosis (RN) was determined by imaging or pathology. Overall survival (OS) was estimated using Kaplan-Meier methodology. Univariate and multivariate Cox proportional hazard models for OS were constructed. Bivariable associations with RN were estimated using fisher exact tests. 99 patients (median age 56 yrs, median KPS 80) were treated with reirradiation (median followup 7.4 mo). Median time between initial and reirradiation was 20 months (range, 2 – 214 mo). Median received dose at reirradiation was 41.4 Gy (30.6 – 60 Gy) to a median planning target volume (PTV) of 183 cc (16 – 825 cc). Median cumulative maximum dose to the optics and brainstem were 54 Gy (4 – 103 Gy) and 76 Gy (5 – 146 Gy), respectively. Median OS was 9 mo (95% CI 6.2 – 10.6 mo). On univariate analysis, time between initial and reirradiation ≥24 mo (HR 0.58, CI 0.36 – 0.94) and reirradiation dose ≥41.4 Gy (HR 0.56, CI 0.35 – 0.88) were associated with longer OS. On multivariate analysis, interval between radiation sessions (HR 0.56, CI 0.34 – 0.91) and higher reirradiation dose (HR 0.55, CI 0.35 – 0.87) remained associated with OS. No cases of radiation injury to the optics or brainstem were reported. 10% of patients experienced RN. Reirradiation dose ≥41.4 Gy, reirradiation PTV ≥200 cc and interval between radiation sessions < 24 mo were not significantly associated with RN. These data support the safety and efficacy of fractionated reirradiation for recurrent GBM including for large tumors. This study suggests that higher reirradiation dose may be feasible, including for large treatment volumes.

Risk of Cardiovascular Disease in Patients With Classical Hodgkin Lymphoma: A Danish Nationwide Register-Based Cohort Study.

Risk of cardiovascular disease (CVD) in patients with classical Hodgkin lymphoma (cHL) undergoing contemporary treatment is unclear. cHL patients ≥ 18 years at diagnosis treated with doxorubicin-containing chemotherapy between 2000 and 2022 were matched 1:5 with comparators on birth year, sex, and Charlson Comorbidity Index at time of matching (score of 0 or ≥ 1). Cause-specific cumulative incidence of a composite of CVDs with corresponding 95% confidence intervals (CIs) were computed with death and lymphoma relapse as competing events (i.e., by censoring individuals at such occurrences) using the Aalen-Johansen estimator. A total of 1905 patients and 9525 comparators with a median follow-up of 10 years (interquartile range, [IQR]: 5.9-17.4). Median age was 39 years (IQR: 27-56), median cumulative doxorubicin dose was 250 mg/m2 (IQR: 200-300). The CVD cumulative incidences were 4.7% (95% CI: 3.6-5.7) for patients versus 2.6% (95% CI: 2.3-2.9) for comparators at 5 years, 8.9% (95% CI: 7.2-10.5) versus 5.5% (95% CI: 4.9-6.0) at 10 years, and 17.0% (95% CI: 14.1-19.9) versus 8.2% (95% CI: 7.4-9.0) at 15 years. CVD remains a substantial effect after contemporary treatment for cHL, suggesting that awareness of symptoms and a low threshold for referral to diagnostic examination are still important measures during survivorship.

Evaluation of Crushed Posaconazole Delayed Release Tablets in Lung Transplant Recipients.

Invasive fungal infections can cause serious complications after lung transplant; therefore, prophylaxis with posaconazole is common. The posaconazole delayed-release (DR) tablet is preferred. Although the package insert states DR tablets cannot be crushed, recent data suggest it is reasonable. We hypothesized that crushed posaconazole DR tablets could reach therapeutic levels in lung transplant recipients. A retrospective study of lung transplant recipients between January 2018 and July 2023, who received crushed posaconazole DR for at least 5 days was completed. Posaconazole troughs were evaluated, and differences were compared between subjects who were therapeutic to those who were subtherapeutic. A cost analysis was also performed. Thirty subjects received crushed posaconazole DR and 50% were therapeutic. The median trough was 1mg/L for those who were therapeutic and 0.4mg/L for those who were not (p < 0.001). The median cumulative dose was 2000mg, and there were no significant differences in the incidence of diarrhea or tube feeds. More subjects in the therapeutic group were loaded (33%vs. 13%), although this was not statistically significant (p = 0.39). No subjects had breakthrough aspergillus one month after starting crushed therapy. Crushed posaconazole DR tablets are a viable and cost savings option, but loading doses and higher maintenance doses may be required to reach therapeutic levels. Those who received loading doses (intravenously or crushed) followed by a daily crushed dose of 400mg were more likely to be therapeutic. Limitations of our study include that it is single-center, small in sample size, and retrospective.

CT surveillance for type 1 autoimmune pancreatitis: cumulative radiation dose and diagnostic performance for disease relapse.

Long-term follow-up is essential for type 1 autoimmune pancreatitis (AIP) patients due to high relapse rates. The cumulative radiation dose from repeated CT scans during follow-up should not be ignored. We aim to investigate the cumulative radiation dose in AIP patients undergoing CT surveillance and the diagnostic performance of CT in detecting disease relapse. The diagnostic performance of MRI from a secondary cohort during the same period was also investigated. This retrospective single-institutional study included 247 type 1 AIP patients with one or more follow-up CT scans, and 120 patients with MR follow-ups. Four metrics were utilized to report the radiation dose, including the volume computed tomography dose index, the dose length product, size-specific dose estimate and effective dose. The diagnostic performance for AIP relapse was assessed, taking the final clinical diagnosis in retrospect as the reference standard. With a median 2.3-year follow-up period, AIP patients followed up with CT exhibited a median cumulative radiation dose of 37.5 mSv. 11.3% of patients have accumulated doses exceeding 100 mSv. For the 169 patients followed over a year, 30.8% sustained an average annual radiation dose surpassing 20 mSv. The sensitivity/specificity/accuracy of CT for detecting abdominal organ relapse was 64.1%/99.6%/97.0%. For AIP patients followed up with MRI, the sensitivity for detecting disease relapse was 90.5%. Considering the accumulation of radiation dose in AIP patients and the insufficient sensitivity in detecting disease relapse with CT, safer and more sensitive imaging follow-up strategies should be explored. Question CT, as the primary imaging modality for autoimmune pancreatitis (AIP) follow-up, raises concerns regarding radiation exposure and lacks reported diagnostic performance in detecting AIP relapse. Findings CT in AIP follow-up causes significant cumulative radiation exposure and exhibits insufficient sensitivity in relapse detection. Clinical relevance Type 1 AIP necessitates long-term imaging follow-up, yet current guidelines lack consensus regarding the prioritization of CT or MRI for such follow-up. CT is widely used but has radiation concerns and limited sensitivity, calling for safer, efficient strategies.

Association Between ABCC2 -24C>T and Nab-Paclitaxel-induced Peripheral Neuropathy in Japanese Patients With Pancreatic Cancer.

Nab-paclitaxel is used to treat patients with pancreatic cancer. However, it frequently induces peripheral neuropathy. Notably, pharmacokinetic factors may be associated with neuropathic symptoms as the onset depends on the cumulative dose. Therefore, we prospectively examined the association between the cumulative dose of nab-paclitaxel at the onset of peripheral neuropathy and polymorphisms of hepatic transporter genes. Patients with pancreatic cancer receiving nab-paclitaxel (125 mg/m2) and gemcitabine (1,000 mg/m2) were enrolled. Peripheral neuropathy was assessed using the Common Terminology Criteria for Adverse Events (CTCAE), Patient-Reported Outcomes CTCAE (PRO-CTCAE), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), every 2-12 weeks, and every 4 weeks thereafter. solute carrier organic anion transporter family member 1B1 (SLCO1B1) 521T>C, 388A>G; SLCO1B3 rs11045585; ATP-binding cassette transporters, subfamily B, member 1 (ABCB1) 1236C>T, 2677G>T/A, 3435C>T; ABCC1 rs2644983; ABCC2 24C>T; and ABCG2 421C>A were analyzed by direct sequencing. Correlations between transporter genotypes and cumulative dose at symptom onset were assessed using Kaplan-Meier and log-rank tests. In total, 25 patients were enrolled. The lowest median cumulative dose for nab-paclitaxel at peripheral neuropathy onset using PRO-CTCAE was 593 mg. By CTCAE it was 800 mg, and by FACT/GOG-Ntx it was 1,090 mg (p<0.0001). At symptom onset, patients with ABCC2 -24C/T genotype had received a significantly lower median cumulative dose by PRO-CTCAE (540 mg) than those with C/C (720 mg) (p=0.0188). However, the other polymorphisms studied were not associated with symptoms. Herein, we found for the first time that ABCC2 -24C/T genotype was significantly associated with the onset of nab-paclitaxel-induced peripheral neuropathy detected with PRO-CTCAE.

Risk of cardiovascular disease in Hodgkin lymphoma patients

Abstract Background Cardiovascular diseases are recognized as some of the most common and problematic late complications to the treatment of Hodgkin lymphoma (HL). However, the anticipated risk is predominantly based on studies of patients treated several decades ago with treatment regimens considered outdated by todays standard. Purpose To describe the risk of cardiovascular disease in HL patients undergoing contemporary treatment regimens and comparing this risk to matched comparators. Methods A register-based cohort study including all Danish HL patients ≥18 years at diagnosis, treated with anthracycline-containing chemotherapy between 2000 and 2022. Index date was defined as date of HL diagnosis. Matching with comparators from the background population was performed in a 1:5 ratio on age, sex, and comorbidities. Patients and comparators with malignancy and/or heart disease prior to the index date were excluded. The primary outcome was a composite endpoint of cardiovascular diseases: heart failure, ischemic heart disease, diseases of the aortic-, mitral-, and tricuspid valve, constrictive pericarditis, cardiomyopathies, atrial and ventricular arrythmias, or any invasive procedures related to these diagnoses. Follow-up began at index date and ended upon event, relapse, death, emigration, or end of follow-up (December 31, 2022), whichever occurred first. The cause-specific cumulative incidence of the primary outcome was computed with all-cause death and lymphoma relapse as competing events using the Aalen-Johansen estimator. Exploratory multivariable Cox regression analyses were performed to identify risk factors for cardiovascular disease among patients with HL. Risk factors were adjusted for sex, age, and comorbidities. Results A total of 1,917 HL patients and 9,585 matched comparators were included. Median age at diagnosis was 39 years (interquartile range [IQR]: 27-56), 57% were male, and median follow-up time was 10.2 years (IQR: 5.3-15.5). The majority of patients were treated with ABVD (83%) and the estimated median cumulative anthracycline dose was 250 mg/m2 (IQR: 200-300). During the study period, 50% of patients received radiotherapy. The cause-specific cumulative incidence of the primary outcome was higher among HL patients compared with comparators across follow-up: 3.7% (95% confidence interval: 2.8-4.6) vs. 2.0% (95% CI: 1.7-2.3) at 5 years, 7.2% (95% CI: 5.7-8.7) vs. 4.6% (95% CI: 4.1-5.1) at 10 years, and 14.2% (95% CI 11.6-16.9) vs 6.7% (95% CI: 6.0-7.5) at 15 years (Figure 1). Risk factors associated with development of heart disease in HL patients were history of hypertension (HR=1.81, 95% CI 1.15-2.84) and male sex (HR=2.01, 95% CI 1.39-2.91) (Figure 2). Conclusions The long-term risk of cardiovascular disease is still high in patients with HL after contemporary treatment suggesting that the use of modern radiotherapy has not eliminated the excess risk of cardiovascular disease.

Sublingual Administration of Tacrolimus is Safe and Provides Similar Drug Exposure to Per-oral Route in Liver Transplant Recipients During Early Postoperative Period–A Large, Retrospective, Observational Study

BackgroundPer-oral(PO) administration of Tacrolimus(TAC) results in inadequate trough levels in early post-operative period in liver-transplant(LT) recipients who undergo Roux-en-Y hepaticojejunostomy for biliary reconstruction. Sublingual administration(SL) of tacrolimus provides an alternative route in such patients. ObjectiveTo assess feasibility and safety of SL tacrolimus in adult LT-recipients in early post-operative period and to compare therapeutic efficacy of SL administration of tacrolimus vs.PO route. Patients and MethodSingle-centre, retrospective, observational study carried out in adult living donor liver transplant(LDLT) recipients between January 2022 till December 2022. Recipients who underwent Roux-en-Y hepaticojejunostomy for biliary reconstruction, received tacrolimus through SL route till post-operative day(POD)5 as they were kept nil per oral constituted the study group while recipients who underwent duct-to-duct(D-D) anastomosis for biliary reconstruction were allowed orally from POD1 and received PO-tacrolimus were chosen as controls. Feasibility and safety of SL-Tacrolimus was assessed in terms of patient acceptance, need to discontinue SL-Tacrolimus, incidence of local adverse effects and systemic adverse events like neurotoxicity and nephrotoxicity. Therapeutic efficacy was evaluated by comparing median trough levels(TAC level) achieved and incidence of graft rejection between two groups. Results212 patients underwent LT during the study period of which 125 were included(58 in SL-group and 67 in PO-group). Both groups had comparable baseline characteristics. In SL-group, all patients tolerated SL-Tacrolimus well and no local adverse events were observed. Patients with SL-Tacrolimus administration achieved higher median TAC level(ng/ml) vs.PO route(5.85 vs 5(p=0.06)) despite similar median cumulative tacrolimus dose before assessing TAC-level. 50% patients achieved TAC level ≥6ng/ml in SL-group vs. 35.8% in PO-group(p=0.14). Incidence of neurotoxicity, nephrotoxicity and graft rejection during hospital stay were similar in both the groups(p=0.56,0.82 and 0.28 respectively). ConclusionSL-tacrolimus is safe and provides similar trough levels to PO-tacrolimus and may be considered as viable alternative whenever inadequate TAC-levels are anticipated through per-oral route.

Liver fibrosis in inflammatory arthritis patients treated with methotrexate and hydroxychloroquine: A FIB-4 index analysis.

To evaluate the risk of liver fibrosis and associated factors with the non-invasive fibrosis score-4 (FIB-4) index in patients with inflammatory arthritis using methotrexate (MTX). Patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) who were followed up in the rheumatology outpatient clinic, who were on methotrexate only and for whom FIB-4 index was could be calculated at methotrexate initiation and follow-up were included. The FIB-4 index was calculated according to the following formula: age (years) × AST(IU/L)/(platelet count(10 (9)/L) × √ALT(IU/L)). The patients' demographics, comorbidities, other treatments, cumulative MTX dose, and reasons for MTX cessation were assessed. For the multivariate analysis, possible factors associated with intermediate-high risk FIB-4 index at last visit were determined. A total of 107 patients were enrolled in the study, of whom 82 (76.6%) had RA and 25 (23.4%) had PsA. At the initiation of MTX, 24 (22.4%) patients had intermediate-high risk FIB-4 index. Comorbidities and the rate of ≥3-4 Charlson comorbidity index were more common in patients with intermediate-high risk FIB-4 index. A total of 37 (34.5%) patients had intermediate-high risk FIB-4 index at the last visit after median 3.6 (0.3-22.06) years follow-up. The median cumulative MTX dose was 2550 mg (1050-13.991). Cumulative MTX dose [OR 1.18 (1.01-1.33), p = .03] and diabetes mellitus [OR 4.60 (1.74-12.50), p = .002] were associated factors with intermediate-high risk FIB-4 index. The concomitant use of hydroxychloroquine (HCQ) was found to be a low-risk factor for FIB-4 index [OR 0.28 (0.10-0.78) p = .015]. The FIB-4 index is a non-invasive method that can be used in daily rheumatology practice for the evaluation and follow-up of patients who will use methotrexate. Comorbidities and cumulative MTX dose seem to be related with the risk of liver fibrosis. Concomitant use of HCQ with MTX may reduce the risk of liver fibrosis.

Outcomes of Adjunctive Corticosteroid Treatment on Hypoxemic Adults Hospitalised for Mycoplasma pneumoniae Pneumonia: a Retrospective Cohort Study.

Corticosteroids appears to be beneficial for severe Mycoplasma pneumoniae pneumonia in children but data in adults are limited. This study investigated effects of adjunctive corticosteroids in hypoxemic adults with M. pneumoniae pneumonia. Adults admitted 2013-2017 with verified M. pneumoniae pneumonia and hypoxemia (SpO2<93% or oxygen treatment) were included in a cohort. Treatment was defined as receipt of at least one glucocorticoid dose.Primary outcome was time to regression of hypoxemia, analysed with a multivariable Cox regression. Secondary outcomes included fever duration, length of stay, and complications. Corticosteroids were given to 31% (122/388) during hypoxemia. Median age was 44 (IQR 34-57) years. Median time to start of corticosteroid treatment was 1.9 (IQR 0.6-3.6) days from admission. Median cumulative dose was equivalent to 15 (IQR 10-19) mg betamethasone. Treatment duration was 5 (IQR 3-6) days. Patients treated with corticosteroids had more severe respiratory disease, longer symptom duration and were more often treated with fluoroquinolones.Time to regression of hypoxemia (HR 0.92 [95% CI 0.72-1.19], P = 0.53) and length of stay (HR 0.91 [95% CI 0.71-1.16], P = 0.44) were not significantly different between corticosteroid treated and controls. Corticosteroid treatment was associated to shorter fever duration (HR 1.44 [95% CI 1.00-2.06], P = 0.046). Complications did not differ significantly between treatment groups. Adjunctive corticosteroids were not associated with reduced time to regression of hypoxemia in adults with M. pneumoniae pneumonia. However, duration of fever was shorter and no increase in complications was seen.

Efficacy of cumulative cisplatin dose on survival in patients with locally advanced cervical cancer treated with definitive chemoradiotherapy: multicenter study by Turkish Oncology Group

ObjectiveTo investigate the impact of cumulative cisplatin dose on clinical outcomes in locally advanced cervical cancer patients undergoing definitive chemoradiotherapy.MethodsA retrospective analysis was conducted on 654 patients with stage IB3–IVA...

Reirradiation of Utracentrally Located Thoracic Tumors Using a 10-Fraction Hypofractionated Stereotactic Body Radiation Therapy Course: A Detailed Dosimetric Analysis

PurposeThere is very little information detailing outcomes and toxicity following re-irradiation for ultracentrally located thoracic tumors, and detailed dosimetric data is non-existent. This data is critical for the safe management of these extremely difficult cases. Materials and MethodsThe records of fifteen individuals undergoing 10-fraction hypofractionated stereotactic body radiotherapy (hfSBRT) for the management of ultracentrally located thoracic tumors between 2009 and 2020 at a single institution were retrospectively reviewed. Treatment outcomes and toxicity were analyzed. A detailed dosimetric analysis of treatment plans and centrally located organs at risk (OARs), from the initial, re-irradiation, and cumulative radiotherapy courses was presented. ResultsAt a median follow up of 10 months, one- and three-year overall survival (OS), progression free survival (PFS) and local control (LC) were 52% and 28%, 33% and 28%, and 76% and 61%, respectively. Treatment related adverse events were low with 5 individuals (33%) developing ≥ grade 2 pneumonitis (Grade 2 = 4, Grade 3 = 1). Dosimetric parameters were not associated with the development of clinically relevant pneumonitis. No adverse events involving central OARs (esophagus, great vessels, primary bronchial tree) were identified. Median cumulative mean lung dose (MLD) was 24 Gy (EQD2) (range: 10-33 Gy), with a V20 of 33% (range: 11-51%). Median esophageal, primary bronchial tree, and great vessel maximum doses (Dmax) were 93.2 Gy (EQD2) (range: 50-148 Gy), 163 Gy (range: 77-204 Gy), and 191 Gy (range: 129-262 Gy), respectively. ConclusionsThe current investigation is the first to provide detailed cumulative dosimetric data from a cohort of patients comprised entirely of ultracentrally located thoracic tumors. Despite unfavorable anatomic tumor location given an intimate association to critical OARs, delivering an ablative dose with a 10-fraction hfSBRT course can serve as a feasible option for these challenging cases.

Long-term safety profile and secondary effectiveness of canakinumab in pediatric rheumatic diseases: a single-center experience

ABSTRACT Background To demonstrate the long-term safety profile of canakinumab over a nine-year period by documenting adverse events in patients with various pediatric rheumatic diseases. Research design and methods This retrospective observational study was conducted at the Pediatric Rheumatology Department of Istanbul University Cerrahpasa between 2015 and 2023. The analysis concerned individuals who had been administered canakinumab treatment for at least six months. The exposure-adjusted event rates were calculated as adverse events per 100 patient days and were compared among three groups based on the cumulative canakinumab dose of <35 mg/kg, 35–70 mg/kg, and >70 mg/kg. Results Among 189 patients, the median exposure time to canakinumab was 2.9 (1.5–4.1) years, corresponding to 573.4 patient years. The median cumulative dose of canakinumab was 2205 (1312–3600) mg. The most common adverse event was upper respiratory tract infection (0.76), followed by urinary tract infection (0.02), pneumonia (0.009), latent tuberculosis (0.009) and lymphadenitis (0.004). A total of 55 serious adverse events (0.025) were reported, 12 (0.006) of which led to drug discontinuation. The event rate of macrophage activation syndrome and disease exacerbation was statistically higher in patients receiving <35 mg/kg cumulative canakinumab dose (p < 0.05). Conclusions An increase in side effect was not observed with the increasing cumulative doses of canakinumab. Canakinumab demonstrated long-term safety with appropriate indication and monitoring.

Salvage radiotherapy for locally recurrent cervical and endometrial carcinoma: clinical outcomes and toxicities

BackgroundThe management of locally recurrent gynecological carcinoma remains a challenge due to the limited availability of data. This study aims to share our institutional experience in using definitive radiotherapy (RT) for the treatment of locally recurrent cervical and endometrial carcinoma.MethodsThe study retrospectively reviewed 20 patients in our hospital completing salvage 3D image-based HDR brachytherapy, with or without EBRT, for locally recurrent cervical and endometrial carcinoma after surgery. The Kaplan–Meier method was applied to estimate the disease-free survival (DFS) and overall survival (OS). The toxicities were assessed by CTCAEv5.ResultsDuring a median observation period of 21 months, the study reported a tumor objective response rate of 95%. The 3-year DFS and OS rates were 89.4% and 90.9%, respectively. The EBRT combined with brachytherapy achieved a median cumulative dose of 88 Gy to CTV D90. 14 patients received concurrent and/or systemic chemotherapy. Two patients suffered locoregional recurrence after salvage treatment, one of whom only received salvage brachytherapy for prior RT history. The analysis identified significant predictors for DFS, including tumor histology and FIGO stage. 5 patients observed acute grade 1–2 rectal (15%) or genitourinary (10%) toxicities. Late toxicities including grade 1–2 rectal bleeding (10%) and grade 2 pelvic fracture (5%) were seen in 3 patients.Conclusions3D image-guided brachytherapy combined with EBRT shows effective tumor control and acceptable toxicity profile for women with locally recurrent gynecologic cancer. The success in managing vaginal recurrence is notably influenced by histologic subtype and FIGO staging.

Comparison of liposomal gel with and without addition of chamomile for prevention of radiation dermatitis in head and neck cancer patients: A randomized controlled trial

Background and purposeHead and neck cancer patients frequently develop radiation dermatitis (RD) during radiotherapy. We compared liposomal gel with and without chamomile extract for the prevention and management of RD in head and neck cancer patients undergoing radiotherapy. Materials and methodsSixty participants undergoing radiotherapy for the first time for head and neck cancer were recruited in a double-blind randomized clinical trial. Primary outcomes were the occurrence of dry desquamation and the cumulative dose of ionizing radiation at the first occurrence of dry desquamation. Secondary outcomes were the occurrence of erythema, moist desquamation, global RD, and participant self-reported symptoms. ResultsDry desquamation occurred in 76.9 % (95 % CI: 57.9, 89.0) of participants in the chamomile liposomal gel group and in 88.9 % (95 % CI: 71.9, 96.1) in the liposomal gel group (p = 0.43). The median cumulative dose of ionizing radiation when dry desquamation occurred was 48.0 Gy in the chamomile liposomal gel group and 40.0 Gy in the liposomal gel group. Fewer symptoms were reported in the chamomile liposomal gel group. ConclusionNo statistically significant differences in outcomes were found between the two groups, though the chamomile liposomal gel group presented with lower grades of RD than the liposomal gel group. In addition, when compared to the literature on other topical interventions to manage RD, our results show that chamomile liposomal gel has potential for better management and prevention of RD in this population, which should be further tested. This study provides crucial information to design future studies.Clinical Trials Registration (REBEC): RBR-92cts3.

Dysglycaemia in Ebola virus disease: a retrospective analysis from the 2018 to 2020 outbreak

BackgroundEbola virus disease (EVD) is associated with multisystem organ failure and high mortality. Severe hypoglycaemia is common, life-threatening, and correctable in critically ill patients, but glucose monitoring may be limited in EVD treatment units. MethodsWe conducted a retrospective review of patients admitted to EVD treatment units in Butembo and Katwa, Eastern DRC. Glucose measurements were done using a handheld glucometer at the bedside or using the Piccolo xpress Chemistry Analyzer on venous samples. Findings384 patients (median age 30 years (interquartile range, IQR, 20-45), 57% female) and 6,422 glucose measurements (median 11 per patient, IQR 4 to 22) were included in the analysis. Severe hypoglycaemia (≤2.2mmol/L) and hyperglycaemia (>10mmol/L) were recorded at least once during the ETU admission in 97 (25%) and 225 (59%) patients, respectively. A total of 2,004 infusions of glucose-containing intravenous solutions were administered to 302 patients (79%) with a median cumulative dose of 175g (IQR 100 to 411). The overall case fatality rate was 157/384 (41%) and was 2.2-fold higher (95%CI 1.3 to 3.8) in patients with severe hypoglycaemia than those without hypoglycaemia (p=0.0042). In a multivariable Cox proportional hazards model, periods of severe hypoglycaemia (adjusted hazard ratio (aHR) 6.2, 95%CI 3.2-12, p<0.0001) and moderate hypoglycaemia (aHR 3.0, 95%CI 1.9-4.8, p<0.0001) were associated with elevated mortality. InterpretationHypoglycaemia is common in EVD, requires repeated correction with intravenous dextrose solutions, and is associated with mortality. FundingThis study was not supported by any specific funding.

Concurrent epirubicin and trastuzumab use increases complete pathological response rate without additional cardiotoxicity in patients with human epidermal growth factor receptor 2-positive early breast cancer: A meta-regression analysis.

Due to cardiotoxicity concerns, the concurrent use of epirubicin and trastuzumab has not been fully studied. This study aimed to examine the cardiotoxicity and pathological complete response (pCR) rate associated with the concurrent regimens in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC). We conducted a systematic search for relevant literature in the NCBI/PubMed, the Cochrane database, and international conference abstracts for phase II or III randomized controlled trials between January 1, 2000, and February 28, 2021, focusing on the concurrent regimens in patients with HER2-positive EBC. To compare the risk of cardiotoxicity and the odds of the pCR rate, we performed linear meta-regression analyses to investigate the effects of multiple covariates. We analyzed 7 neoadjuvant trials involving the concurrent use of epirubicin and trastuzumab with 1797 patients. The median cumulative dose of epirubicin used was 300 mg/m2, with a total of 96 reported adverse cardiac events. The concurrent regimens did not result in a significant increase in cardiotoxicity compared to nonconcurrent regimens (risk ratio [RR] = 1.18, 95% confidence interval [CI] = 0.68-2.05). Compared with nonconcurrent or non-anthracycline-containing regimens, concurrent regimens were associated with a significant increase in the pCR rate (odds ratio = 1.48, 95% CI = 1.04-2.12). The linear fixed-effects meta-regression analysis indicated that in trials including more patients with hormone receptor-positive EBC, the RR of cardiotoxicity significantly increased with concurrent regimens, and the pCR rate became less significant. The combination of trastuzumab and a low dose of epirubicin positively impacted the pCR rate without a significant increase in cardiotoxicity. We recommend exploring concurrent regimens for HR-negative, HER2-positive tumors to enhance pCR rates, with caution advised for HR-positive tumors due to potential cardiotoxicity.

Addressing Glucocorticoid-Related Problems with the Clinical Pharmacist Collaboration in Rheumatology Practice: A Prospective Follow-Up Study.

Glucocorticoids (GCs) play a crucial role in the treatment of many rheumatic diseases regarding their anti-inflammatory and immunosuppressive effects. Inappropriate use of GCs can exacerbate GC-related problems besides complex treatment regimens and miscellaneous well-established adverse events. Although several guidelines exist for managing these problems, there is lack of real-life studies evaluating the problems at the patient level. This study aims to identify GC-related problems among patients with rheumatic diseases and address how they have been solved. This prospective follow-up study was conducted between January 2021 and June 2022 at a university rheumatology outpatient clinic and included patients using GCs. A clinical pharmacist assessed patients for possible GC-related problems at baseline, 3 months, and 6 months. Identified problems, their causes, interventions to address these problems, and their outcomes were categorized using the Pharmaceutical Care Network Europe (PCNE v9.1) classification system. The resolution of the problems was evaluated at the patient's next follow-up visit. A total of 156 patients were included, and 236 GC-related problems were identified in 66% of the patients. Adverse drug events (possible) accounted for the highest proportion of GC-related problems (94.1%), and the most common causes were lack of laboratory monitoring of GC-related adverse events (41.5%) and lack of drug treatment despite existing indications (39.8%). The median cumulative prednisolone dose was higher in patients with GC-related problems (3115 vs. 5455 mg, p = 0.007). The clinical pharmacist suggested 381 interventions: 47.7% (n = 182) at the 'prescriber level', 31.8% (n = 121) at the 'patient level', and 20.5% (n = 78) at the 'drug level'. Of those interventions, 98% were accepted, and 80.1% of the problems were solved. This study showed that the prevalence of GC-related problems is high in patients with rheumatic diseases. Integrating clinical pharmacists into the multidisciplinary rheumatology team provides an advantage in effectively identifying and managing GC-related problems at an early stage.

QOL-27. EARLY CHEMOTHERAPY-INDUCED HEARING LOSS IN CHILDREN WITH MEDULLBLASTOMA AND EMBRYONAL BRAIN TUMOURS

Abstract BACKGROUND The purpose of this study was to examine the prevalence, severity and time to develop Chemotherapy-induced hearing loss (HL) in a cohort of embryonal brain tumors(ET) treated with cisplatin and cranial radiation(RT). METHODS Our cohort included children 3-15years treated between January2022 and June2023 for medulloblastoma and other ETs with surgery, craniospinal RT and 6 cycles of CET chemotherapy (cyclophosphamide,vincristine,cisplatin). Cisplatin 75mg/m2 was given in alternate cycles with a cumulative dose of 225 mg/m2. Children underwent clinical evaluation and age-appropriate audiological assessment at diagnosis,every 1-2cycles of cisplatin and end-of-treatment. Grading of ototoxicity was done per SIOP-Boston grading. Children with grade2 and above HL did not receive further cisplatin.Children with grade1HL underwent frequent monitoring.For this study, pure-tone-audiometry from start of treatment to end of treatment were analyzed and ≥Grade2HL was considered significant. RESULTS A total of 63 children were included in the study, 28(44.%)female, median age 7years (range 3-15years). Twenty (31.7%) children developed &amp;gt;grade2HL; the worse ear had grade 4 HL in 1(1.6%),grade 3 in 13(20.6%) and grade 2 in 6(9.5%).One had grade 2HL and 4 had grade 1HL even prior to start of cisplatin.The median cumulative cisplatin dose at developing &amp;gt;grade2HL was 0mg/m2(n=1), 75mg/m2(n=8), 150mg/m2(n=3) and 225mg/m2(n=9; 5 at end-of-treatment and 4 at follow-up). Age, gender and diagnosis were not associated with development of HL. CONCLUSION The high prevalence of early-onset ototoxicity in children with embryonal brain tumours is concerning.We recommend close monitoring of hearing function,at least every 2 cycles of cisplatin chemotherapy, if not more frequently. Incorporation of pharmacogenomics to identify highly susceptible individuals and therapeutic interventions such as cessation of cisplatin or replacement with alternatives in early ototoxicity would help reduce a potentially life-altering and long-term health concern.

Malignancy in systemic lupus erythematosus: relation to disease characteristics in 92 patients – a single center retrospective study

ObjectiveSystemic lupus erythematosus (SLE) is a chronic autoimmune disease with a variable clinical manifestation, potentially leading to death. Importantly, patients with SLE have an increased risk of neoplastic disorders. Thus, this study aimed to comprehensively evaluate the clinical and laboratory characteristics of patients with SLE and with or without malignancy.MethodsWe conducted a retrospective analysis of medical records of 932 adult Caucasian patients with SLE treated at the University Hospital in Kraków, Poland, from 2012 to 2022. We collected demographic, clinical, and laboratory characteristics, but also treatment modalities with disease outcomes.ResultsAmong 932 patients with SLE, malignancy was documented in 92 (9.87%), with 7 (7.61%) patients experiencing more than one such complication. Non-hematologic malignancies were more prevalent (n = 77, 83.7%) than hematologic malignancies (n = 15, 16.3%). Patients with SLE and malignancy had a higher mean age of SLE onset and a longer mean disease duration than patients without malignancy (p < 0.001 and p = 0.027, respectively). The former group also presented more frequently with weight loss (odds ratio [OR] = 2.62, 95% confidence interval [CI] 1.61–4.23, p < 0.001), fatigue/weakness (OR = 2.10, 95% CI 1.22–3.77, p = 0.005), and fever (OR = 1.68, 95% CI 1.06–2.69, p = 0.024). In the malignancy-associated group, we noticed a higher prevalence of some clinical manifestations, such as pulmonary hypertension (OR = 3.47, 95% CI 1.30–8.42, p = 0.007), lung involvement (OR = 2.64, 95% CI 1.35–4.92, p = 0.003) with pleural effusion (OR = 2.39, 95% CI 1.43–3.94, p < 0.001), and anemia (OR = 2.24, 95% CI 1.29–4.38, p = 0.006). Moreover, the patients with SLE and malignancy more frequently had internal comorbidities, including peripheral arterial obliterans disease (OR = 3.89, 95% CI 1.86–7.75, p < 0.001), myocardial infarction (OR = 3.08, 95% CI 1.41–6.30, p = 0.003), heart failure (OR = 2.94, 95% CI 1.30–6.17, p = 0.005), diabetes mellitus (OR = 2.15, 95% CI 1.14–3.91, p = 0.011), hypothyroidism (OR = 2.08, 95% CI 1.29–3.34, p = 0.002), arterial hypertension (OR = 1.97, 95% CI 1.23–3.23, p = 0.003), and hypercholesterolemia (OR = 1.87, 95% CI 1.18-3.00, p = 0.006). Patients with SLE and malignancy were treated more often with aggressive immunosuppressive therapies, including cyclophosphamide (OR = 2.07, 95% CI 1.30–3.28, p = 0.002), however median cumulative cyclophosphamide dose in malignancy-associated SLE subgroup was 0 g (0–2 g). Interestingly, over a median follow-up period of 14 years (ranges: 8–22 years) a total of 47 patients with SLE died, with 16 cases (5.28%) in the malignancy-associated SLE group and 31 cases (5.73%) in the non-malignancy SLE group (p = 0.76). The most common causes of death were infections (21.28%) and SLE exacerbation (8.51%).ConclusionThe study highlights the relatively frequent presence of malignancies in patients with SLE, a phenomenon that demands oncological vigilance, especially in patients with a severe clinical course and comorbidities, to improve long-term outcomes in these patients.