Treatment-related Complications Research Articles

Infusion Therapies in the Treatment of Parkinson's Disease.

Oral levodopa is the gold-standard therapy for treating Parkinson's disease (PD) but after a few years of treatment the therapeutic window narrows, and patients often experience various treatment-related complications. Patients in this advanced PD stage may benefit from alternative therapy, such as continuous intrajejunal delivery of levodopa-carbidopa intestinal gel (LCIG; or carbidopa-levodopa enteral suspension), continuous intrajejunal delivery of levodopa-carbidopa-entacapone intestinal gel, or continuous subcutaneous apomorphine infusion. Consideration and initiation of infusion therapies in advanced PD are suggested before the onset of major disability. The present review summarizes clinical evidence for infusion therapy in advanced PD management, discusses available screening tools for advanced PD, and provides considerations around optimal use of infusion therapy.

Development and clinical application of a tool to identify frailty in elderly patients with gynecological cancers

ObjectiveFrailty is more reliable than chronological age in predicting the effectiveness and tolerability of treatments in cancer patients. An increasing number of screening tools have been proposed, however none have...

Feature Importance Analysis of a Deep Learning Model for Predicting Late Bladder Toxicity Occurrence in Uterine Cervical Cancer Patients.

(1) In this study, we developed a deep learning (DL) model that can be used to predict late bladder toxicity. (2) We collected data obtained from 281 uterine cervical cancer patients who underwent definitive radiation therapy. The DL model was trained using 16 features, including patient, tumor, treatment, and dose parameters, and its performance was compared with that of a multivariable logistic regression model using the following metrics: accuracy, prediction, recall, F1-score, and area under the receiver operating characteristic curve (AUROC). In addition, permutation feature importance was calculated to interpret the DL model for each feature, and the lightweight DL model was designed to focus on the top five important features. (3) The DL model outperformed the multivariable logistic regression model on our dataset. It achieved an F1-score of 0.76 and an AUROC of 0.81, while the corresponding values for the multivariable logistic regression were 0.14 and 0.43, respectively. The DL model identified the doses for the most exposed 2 cc volume of the bladder (BD2cc) as the most important feature, followed by BD5cc and the ICRU bladder point. In the case of the lightweight DL model, the F-score and AUROC were 0.90 and 0.91, respectively. (4) The DL models exhibited superior performance in predicting late bladder toxicity compared with the statistical method. Through the interpretation of the model, it further emphasized its potential for improving patient outcomes and minimizing treatment-related complications with a high level of reliability.

Challenges and Management Strategies in the Nutrition of Older People with Diabetes

AbstractDiabetes has increased in prevalence and is the most common chronic metabolic disease worldwide. Its incidence and prevalence have particularly increased among older adults over the last few decades. The older adult population older than 60 years is diagnosed chiefly with type 2 diabetes, prediabetes, and type 1 diabetes in a small percentage; there is also an incidence of a transient form of diabetes secondary to chronic underlying diseases or as a part of their treatment-related complications. The primary goal in managing older adults with diabetes is to maintain glycemic status against the risk of hypoglycemia and its complications. In the older adult population, the problem of polypharmacy and nutrition must be kept in mind while achieving glycemic targets and preventing diabetes complications. Few studies have highlighted the importance of nutrition in older adults with diabetes and hypoglycemia as a complication leading to increased morbidity and mortality. Many factors in the older aged groups interplay in diabetes patients. Increasing the risk of hypoglycemia and managing nutritional aspects is paramount in older adults with diabetes mellitus. This review highlights various aspects of nutritional management in older adults with diabetes based on the current evidence available in the literature. However, most dietary recommendations for older adults with diabetes are based on studies in the adult population, and further studies targeting the older adult population are needed.

STUDY TO DETERMINE MULTIMODAL THERAPY IMPACT ON ADRENALECTOMY FOR LOCALIZED ADRENOCORTICAL CARCINOMA AND OVERALL SURVIVAL OF PATIENTS

This study aimed to determine the impact of multimodal therapy on adrenalectomy for localized adrenocortical carcinoma (ACC) and the overall survival of patients. The study included 200 patients. A retrospective analysis was conducted on 200 patients diagnosed with localized ACC who underwent adrenalectomy at a medical center. The patients were divided into the multimodal therapy group (n=100) and the adrenalectomy alone group (n=100). Patient characteristics, treatment modalities, pathological findings, and follow-up data were analyzed. The primary outcome measures included recurrence rates, overall survival rates, and treatment-related complications. The 5-year overall survival rate was significantly higher in Group B (68%) compared to Group A (45%) (p < 0.001). Group B also had a higher 5-year disease-free survival rate (54%) compared to Group A (32%) (p = 0.023). The local recurrence rate was lower in Group B (18%) compared to Group A (32%). Treatment-related adverse events occurred slightly more frequently in Group B (22%) than in Group A (15%) but did not significantly impact patient outcomes. Subgroup analyses consistently showed improved overall survival in Group B across different age groups, tumor stages, and histology. Adding multimodal therapy to adrenalectomy for localized ACC significantly improved overall survival, disease-free survival, and reduced local recurrence rates. Multimodal therapy should be considered a potential treatment approach for improving outcomes in ACC patients. Further studies with larger cohorts and prospective designs are needed to confirm these findings and optimize treatment strategies.

Bayesian analysis of the Substrate Ablation vs. Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia trial.

Bayesian analyses can provide additional insights into the results of clinical trials, aiding in the decision-making process. We analysed the Substrate Ablation vs. Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia (SURVIVE-VT) trial using Bayesian survival models. The SURVIVE-VT trial randomized patients with ischaemic cardiomyopathy and monomorphic ventricular tachycardia (VT) to catheter ablation or antiarrhythmic drugs (AAD) as a first-line strategy. The primary outcome was a composite of cardiovascular death, appropriate implantable cardioverter-defibrillator shocks, unplanned heart failure hospitalizations, or severe treatment-related complications. We used informative, skeptical, and non-informative priors with different probabilities of large effects to compute the posterior distributions using Markov Chain Monte Carlo methods. We calculated the probabilities of hazard ratios (HR) being <1, <0.9, and <0.75, as well as 2-year survival estimates. Of the 144 randomized patients, 71 underwent catheter ablation and 73 received AAD. Regardless of the prior, catheter ablation had a >98% probability of reducing the primary outcome (HR < 1) and a >96% probability of achieving a reduction of >10% (HR < 0.9). The probability of a >25% (HR < 0.75) reduction of treatment-related complications was >90%. Catheter ablation had a high probability (>93%) of reducing incessant/slow undetected VT/electric storm, unplanned hospitalizations for ventricular arrhythmias, and overall cardiovascular admissions > 25%, with absolute differences of 15.2%, 21.2%, and 20.2%, respectively. In patients with ischaemic cardiomyopathy and VT, catheter ablation as a first-line therapy resulted in a high probability of reducing several clinical outcomes compared to AAD. Our study highlights the value of Bayesian analysis in clinical trials and its potential for guiding treatment decisions. ClinicalTrials.gov identifier: NCT03734562.

Effects of artificial tears on keratocyte cell density after femtosecond laser in situ keratomileusis: a prospective, comparative, interventional, contralateral eye study

Background: Flap creation during laser refractive surgery restructures the anterior cornea, particularly the stroma, reducing the keratocyte cell density (KCD). This reduced density makes it challenging to completely regenerate to the presurgical phase. The aim of the present study was to investigate the effects of two types of artificial tear (AT) interventions on KCD up to 3 months after femtosecond laser-assisted in situ keratomileusis (FS-LASIK) surgery. Methods: This prospective, double-blind, comparative, interventional, contralateral eye study recruited patients with myopia scheduled for FS-LASIK. Inclusion criteria were healthy individuals aged 19 – 25 years with moderate or high myopia, a maximum cylindrical error of - 1.25 diopters, and a maximum pupil size of 6.5 mm who had undergone FS-LASIK and completed 3 months of follow-up. Complete optometric and ophthalmologic examinations were performed. Bilateral simultaneous FS-LASIK surgery was performed using the same femtosecond laser platform as in the standard procedure. The Research Randomizer was used to determine the eye to be treated with Systane® Hydration (Alcon Laboratories, Inc., Fort Worth, TX, USA) or Systane® ULTRA (Alcon Laboratories, Inc., Fort Worth, TX, USA) AT. KCD was examined using real-time images obtained from in vivo confocal microscopy (Heidelberg Retina Tomograph 3 with the Rostock Cornea Module, HRT III RCM); Heidelberg Engineering GmbH, Heidelberg, Germany) at baseline and 1- and 3-month postoperative visits. Results: We included 60 eyes of 30 participants with a mean (standard deviation) age of 21.34 (1.85) years and a male-to-female ratio of 1:1 who completed 3-month post-FS-LASIK surgery follow-up. KCD did not differ significantly between the two groups at any visit (all P &gt; 0.05); nevertheless, mean KCD was initially reduced up to 1 month postoperatively and then revealed a slight increase up to 3 months postoperatively in Systane® Hydration-treated eyes and continued to reduce in Systane® ULTRA-treated eyes. Intragroup comparisons revealed that the eyes treated with ATs experienced a significant reduction in KCD between the preoperative and 1-month postoperative visits and between the preoperative and 3-month postoperative visits (all P &lt; 0.05). Treatment-related complications were not observed. Conclusions: Overall, KCD reduced up to 3 months post-FS-LASIK surgery. Both AT types exerted a comparable effect on postoperative KCD up to 3 months. Future studies with a more frequent administration of ATs, longer follow-up periods, and a control group are required before preliminary outcomes of the present study can be generalized.

Cancer patients in the emergency department or intensive care unit: a 20-year bibliometric analysis of research progress and prospects

BackgroundAn increasing number of cancer patients may require emergency and intensive care at diagnosis and throughout their disease course. This study aimed to explore the progress, prospects, collaboration and network of research in the field of emergency and intensive care for cancer patients using bibliometric analysis.MethodsA search of the Web of Science (WOS) database was conducted to identify relevant articles in English published between 2000 and 2022. Bibliometric analysis platform and R-studio software were used for data analysis, which included cluster analysis, word cloud matrix, trend topics, and thematic maps based on author keywords and keywords plus.ResultsA total of 630 articles were included, with an average annual growth rate of 17.1%. The most active country in terms of productivity and collaboration was the United States. Trend topics evolved over time, with COVID-19 and epidemiology among the most recent hot topics. General topics such as palliative care, intensive care, emergency department, chemotherapy, management, and outcomes were identified, as well as specialized topics relating to the most common cancer types, and cancer- or treatment-related complications such as brain metastasis, hyperviscosity syndrome, spinal cord compression, pericardial tamponade, hemorrhage, respiratory failure, septic shock, venous thromboembolism, and malnutrition.ConclusionThere has been a increasing and evolving interest in emergency and intensive care for cancer patients over time.

MDB-08. THYROID HORMONES INHIBIT MEDULLOBLASTOMA PROGRESSION THROUGH INDUCING TUMOR CELL DIFFERENTIATION

Abstract Hypothyroidism is commonly detected in patients with medulloblastoma (MB), a pediatric brain tumor, which is generally considered as a treatment-related complication. Although reduced levels of thyroid hormone (TH) significantly correlate with poor survival of patients with MB, the possible link between TH signaling and MB pathogenicity is unknown. Here, we found that TH plays a critical role in MB pathogenicity through regulating the terminal differentiation of tumor cells. In the absence or with reduced levels of TH, unliganded TRα (a nuclear TH receptor) physically interacts with EZH2 to epigenetically repress the expression of NeuroD1, a transcription factor dictating terminal differentiation of neuronal progenitors and MB cells. However, TH reverses EZH2-mediated repression of NeuroD1 through interfering with the binding between EZH2 and TRα, thereby stimulating terminal differentiation of tumor cells and repressing MB pathogenicity. Moreover, TH promotes extensive differentiation and suppresses the proliferation of tumor cells from different molecular subgroups of MB5 including hedgehog (HH) group as well as group 3 (G3) MB, suggesting that TH-induced differentiation is not restricted by oncogenic mutations in tumor cells. Consequently, TH treatment significantly inhibits the in vivo growth of SHH- and G3-MB via stimulating tumor cell differentiation, with no induction of tumor cell apoptosis or death, indicating that TH signaling represents a novel therapeutic entry-point for broad treatment of MB. These findings elucidate the mechanisms underlying terminal differentiation of MB cells, establish an unprecedented association between TH signaling and MB progression. Our studies provide compelling evidence for a promising tumor therapeutic modality by promoting tumor cell differentiation.

Radiosurgery for ventricular tachycardia (RAVENTA): interim analysis of a multicenter multiplatform feasibility trial

BackgroundSingle-session cardiac stereotactic radiation therapy (SBRT) has demonstrated promising results for patients with refractory ventricular tachycardia (VT). However, the full safety profile of this novel treatment remains unknown and very limited data from prospective clinical multicenter trials are available.MethodsThe prospective multicenter multiplatform RAVENTA (radiosurgery for ventricular tachycardia) study assesses high-precision image-guided cardiac SBRT with 25 Gy delivered to the VT substrate determined by high-definition endocardial and/or epicardial electrophysiological mapping in patients with refractory VT ineligible for catheter ablation and an implanted cardioverter defibrillator (ICD). Primary endpoint is the feasibility of full-dose application and procedural safety (defined as an incidence of serious [grade ≥ 3] treatment-related complications ≤ 5% within 30 days after therapy). Secondary endpoints comprise VT burden, ICD interventions, treatment-related toxicity, and quality of life. We present the results of a protocol-defined interim analysis.ResultsBetween 10/2019 and 12/2021, a total of five patients were included at three university medical centers. In all cases, the treatment was carried out without complications. There were no serious potentially treatment-related adverse events and no deterioration of left ventricular ejection fraction upon echocardiography. Three patients had a decrease in VT episodes during follow-up. One patient underwent subsequent catheter ablation for a new VT with different morphology. One patient with local VT recurrence died 6 weeks after treatment in cardiogenic shock.ConclusionThe interim analysis of the RAVENTA trial demonstrates early initial feasibility of this new treatment without serious complications within 30 days after treatment in five patients. Recruitment will continue as planned and the study has been expanded to further university medical centers.Trial registration numberNCT03867747 (clinicaltrials.gov). Registered March 8, 2019. Study start: October 1, 2019.

Concurrent chemoradiotherapy followed by adjuvant cisplatin–gemcitabine versus cisplatin–fluorouracil chemotherapy for N2–3 nasopharyngeal carcinoma: a multicentre, open-label, randomised, controlled, phase 3 trial

Patients with N2-3 nasopharyngeal carcinoma have a high risk of treatment being unsuccessful despite the current practice of using a concurrent adjuvant cisplatin-fluorouracil regimen. We aimed to compare the efficacy and safety of concurrent adjuvant cisplatin-gemcitabine with cisplatin-fluorouracil in N2-3 nasopharyngeal carcinoma. We conducted an open-label, randomised, controlled, phase 3 trial at four cancer centres in China. Eligible patients were aged 18-65 years with untreated, non-keratinising, stage T1-4 N2-3 M0 nasopharyngeal carcinoma, an Eastern Cooperative Oncology Group performance status score of 0-1, and adequate bone marrow, liver, and renal function. Eligible patients were randomly assigned (1:1) to receive concurrent cisplatin (100 mg/m2 intravenously) on days 1, 22, and 43 of intensity-modulated radiotherapy followed by either gemcitabine (1 g/m2 intravenously on days 1 and 8) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 3 weeks or fluorouracil (4 g/m2 in continuous intravenous infusion for 96 h) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 4 weeks, for three cycles. Randomisation was done using a computer-generated random number code with a block size of six, stratified by treatment centre and nodal category. The primary endpoint was 3-year progression-free survival in the intention-to-treat population (ie, all patients randomly assigned to treatment). Safety was assessed in all participants who received at least one dose of chemoradiotherapy. This study was registered at ClinicalTrials.gov, NCT03321539, and patients are currently under follow-up. From Oct 30, 2017, to July 9, 2020, 240 patients (median age 44 years [IQR 36-52]; 175 [73%] male and 65 [27%] female) were randomly assigned to the cisplatin-fluorouracil group (n=120) or cisplatin-gemcitabine group (n=120). As of data cutoff (Dec 25, 2022), median follow-up was 40 months (IQR 32-48). 3-year progression-free survival was 83·9% (95% CI 75·9-89·4; 19 disease progressions and 11 deaths) in the cisplatin-gemcitabine group and 71·5% (62·5-78·7; 34 disease progressions and seven deaths) in the cisplatin-fluorouracil group (stratified hazard ratio 0·54 [95% CI 0·32-0·93]; log rank p=0·023). The most common grade 3 or worse adverse events that occurred during treatment were leukopenia (61 [52%] of 117 in the cisplatin-gemcitabine group vs 34 [29%] of 116 in the cisplatin-fluorouracil group; p=0·00039), neutropenia (37 [32%] vs 19 [16%]; p=0·010), and mucositis (27 [23%] vs 32 [28%]; p=0·43). The most common grade 3 or worse late adverse event (occurring from 3 months after completion of radiotherapy) was auditory or hearing loss (six [5%] vs ten [9%]). One (1%) patient in the cisplatin-gemcitabine group died due to treatment-related complications (septic shock caused by neutropenic infection). No patients in the cisplatin-fluorouracil group had treatment-related deaths. Our findings suggest that concurrent adjuvant cisplatin-gemcitabine could be used as an adjuvant therapy in the treatment of patients with N2-3 nasopharyngeal carcinoma, although long-term follow-up is required to confirm the optimal therapeutic ratio. National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Major Project of Basic and Applied Basic Research, Sci-Tech Project Foundation of Guangzhou City, Sun Yat-sen University Clinical Research 5010 Program, Innovative Research Team of High-level Local Universities in Shanghai, Natural Science Foundation of Guangdong Province for Distinguished Young Scholar, Natural Science Foundation of Guangdong Province, Postdoctoral Innovative Talent Support Program, Pearl River S&T Nova Program of Guangzhou, Planned Science and Technology Project of Guangdong Province, Key Youth Teacher Cultivating Program of Sun Yat-sen University, the Rural Science and Technology Commissioner Program of Guangdong Province, and Fundamental Research Funds for the Central Universities.

Real world data about stupp platform in the treatment of glioblastoma in a single center of Colombia.

e14065 Background: Glioblastoma cancer is a disease with high mortality reported worldwide. However, in Colombia and Latin America there is a large gap in terms of the information available regarding the characteristics and survival of these patients. Methods: This is an observational, descriptive study of a cohort of patients with glioblastoma cancer who initiated medical treatment at Fundación Santa Fe de Bogotá, a high complexity hospital. We analyzed clinical characteristics, IDH mutation, histology, treatments, progression free survival (PFS), overall survival (OSm) and treatment related complications. We use Kaplan Meier as survival statistic. Results: Twenty patients were included during the 48 months. The average age was 62 years. 65% males, 35% female. IDH mutation detection was performed in 100% of patients, and IDH1 was positive in 20% of the population. Regarding the anatomy location occipital lobe 5%, temporal 20%, parietal 5%, frontal 35%, other locations 35%, ECOG 0-1 were the 100%. Time from start to stupp platform after surgery was 6.1 weeks. All patients received the surgical treatment scheme, later stupp platform followed by temozolamide. In the survival analysis, 15% of patients died during follow-up and 35% progressed to first line. The median overall survival (OSm) 19m, and Progression-free survival (PFS) 14m for the global population. Adjusting survival models for confounding variables, in males the OSm 19 and 15.6m in females. The PDF 15,6m males and 11.8m in females. The OSm in patients with IDH negative 20m, and in the group with IDH1 mutated the OSm has not been reached to 18m of follow-up. Conclusions: Our cohort of patients is similar to the literature reported worldwide, gender may be a predictor of risk. We have good survival times with the stupp platform, rapid access to treatment may be a factor in favor of our good outcomes.

Patients' and Clinicians' Perceptions of the Clinical Utility of Predictive Risk Models for Chemotherapy-Related Symptom Management: Qualitative Exploration Using Focus Groups and Interviews.

Interest in the application of predictive risk models (PRMs) in health care to identify people most likely to experience disease and treatment-related complications is increasing. In cancer care, these techniques are focused primarily on the prediction of survival or life-threatening toxicities (eg, febrile neutropenia). Fewer studies focus on the use of PRMs for symptoms or supportive care needs. The application of PRMs to chemotherapy-related symptoms (CRS) would enable earlier identification and initiation of prompt, personalized, and tailored interventions. While some PRMs exist for CRS, few were translated into clinical practice, and human factors associated with their use were not reported. We aim to explore patients' and clinicians' perspectives of the utility and real-world application of PRMs to improve the management of CRS. Focus groups (N=10) and interviews (N=5) were conducted with patients (N=28) and clinicians (N=26) across 5 European countries. Interactions were audio-recorded, transcribed verbatim, and analyzed thematically. Both clinicians and patients recognized the value of having individualized risk predictions for CRS and appreciated how this type of information would facilitate the provision of tailored preventative treatments or supportive care interactions. However, cautious and skeptical attitudes toward the use of PRMs in clinical care were noted by both groups, particularly in relationship to the uncertainty regarding how the information would be generated. Visualization and presentation of PRM information in a usable and useful format for both patients and clinicians was identified as a challenge to their successful implementation in clinical care. Findings from this study provide information on clinicians' and patients' perspectives on the clinical use of PRMs for the management of CRS. These international perspectives are important because they provide insight into the risks and benefits of using PRMs to evaluate CRS. In addition, they highlight the need to find ways to more effectively present and use this information in clinical practice. Further research that explores the best ways to incorporate this type of information while maintaining the human side of care is warranted. ClinicalTrials.gov NCT02356081; https://clinicaltrials.gov/study/NCT02356081.

EPH27 Association between Prescribing Specialty and Treatment-Related Complications in Patients Using Novel Hormonal Agents for Metastatic Castration-Resistant Prostate Cancer: Population-Based Study

Novel hormonal agents (NHAs) such as abiraterone acetate (ABI) and enzalutamide (ENZ) are frequently used in metastatic castration-resistant prostate cancer (mCRPC). While mCRPC treatment has been traditionally administered by medical oncologists, urologists have also adopted the use of NHAs. The objective was to assess the association between the incidence of NHA-related complications and prescribing specialty in mCRPC patients treated with NHAs.

CDK4/6 inhibitors and cardiovascular toxicity: Real-world evidence.

e15074 Background: Cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) have fundamentally transformed the therapeutic landscape of hormone receptor-positive and human epidermal growth factor receptor 2 (HER2) negative breast cancer, either as monotherapy (abemaciclib) or combined with classic endocrine therapy (ribociclib, abemaciclib, and palbociclib). However, evidence regarding treatment-related cardiovascular complications, beyond the context of clinical trials, remains scarce. Methods: We retrospectively explored the FDA Adverse Events Reporting System (FAERS) to gain insight into both frequency and spectrum of cardiovascular toxicities of these novel targeted agents in real-world setting. Results: For the period January 2018 - September 2022, a total of 90,999 adverse events (AEs) in patients under CDK4/6i have been reported, with 2,739 (3.01%) and 5,176 (5.69%) records being submitted as cardiac and vascular events, respectively. The incidence of these AEs was higher in the case of ribociclib, with arrhythmia representing the main cardiac complication (512 cases), followed by palpitations (120 cases), and acute coronary syndrome (115 cases). Interestingly, there was only one report of QT prolongation; of note, ribociclib has labeling guidance for QTc assessment. Hypertension/hypertensive crisis (302 cases), flushing (251 cases), and thrombotic events (226 cases) -with the exception of pulmonary embolism which was categorized as respiratory AE- comprised the foremost vascular toxicities associated with ribociclib. Conclusions: FAERS displays a public, post-market safety evaluation database with reports from healthcare professionals as well as consumers, yet it may include duplicates, inaccurate information, and fails to confirm causal relationship between the AEs and the medicinal product. In the light of CDK4/6i long-term usage, pharmacovigilance studies are warranted to elucidate their potential cardiovascular hazard. [Table: see text]

Safety and efficacy study of oral metronomic capecitabine in combination with pyrotinib for HER2-positive metastatic breast cancer: A phase II trial.

e13038 Background: A single-arm prospective phase II trial to was conducted evaluate the efficacy and safety of oral metronomic capecitabine combined with pyrotinib in human epidermal growth factor receptor 2-positive (HER2 positive) metastatic breast cancer (MBC) patients. Methods: HER2-positive patients received oral metronomic capecitabine 500 mg three times daily and pyrotinib 400 mg. The primary endpoint was progression-free survival (PFS). Other endpoints included objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and safety. Results: 50 patients with HER2-positive MBC were enrolled, and one was excluded due to medication irregularities. The median PFS and OS were 11.9 months (95%CI 8.8-14.6) and 29.3 months (95%CI 24.4-34.8) respectively. ORR was 34.7%, and CBR was 81.6% with 2 CR (4.1%), 15 PR (30.6%) and 23 SD (46.9%). The mPFS in first- or second-line treatment was 12.2 months. The most frequent treatment-related adverse complications included hand-foot syndrome, diarrhea, vomiting and nausea. Grade 3 adverse events occurred in 15 (30.6%) patients and included hand-foot syndrome (12.2%), diarrhea (12.2%), vomiting (4.1%), and nausea (2.0%). Grade 4 adverse event of diarrhea (2.0%) was observed in one case. Conclusions: The combination of metronomic capecitabine and pyrotinib is a promising regimen with competitive efficacy and improved tolerability in HER2-positive metastatic breast cancer patients. Clinical trial information: NCT03923166 .

The quality of life in nasopharyngeal carcinoma radiotherapy: A longitudinal study

ObjectiveThis article aims to longitudinally compare nasopharyngeal carcinoma (NPC) patients' quality of life (QoL) during radiotherapy (RT) and identify QoL correlates. MethodsThis study included 98 patients, with 85 completing full follow-up. Data were collected at baseline (T1), midpoint of RT (T2), and RT completion (T3), between October 2021 and November 2022. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). RIOM severity was evaluated by the toxicity criteria of Radiation Therapy Oncology Group (RTOG). The nutritional status was evaluated using the Nutritional Risk Screening 2002 (NRS 2002), body mass index (BMI), and the Patient-Generated Subjective Global Assessment (PG-SGA). The generalized estimating equation described the QoL evolution and correlated it with RIOM, nutritional status, and other influential factors. ResultsSignificant deterioration was observed in various subscales of EORTC QLQ-C30 during RT, including global health status (GHS), physical function, role function, emotional function, fatigue, nausea/vomiting, pain, insomnia, appetite loss, and constipation (all P ​< ​0.05). Substantial deterioration was also observed in RIOM, nutritional status, and part of hematological indexes (all P ​< ​0.05). The decline of QoL was associated with gender, age, education level, chemotherapy regimen, Karnofsky performance status (KPS) score, RIOM severity, NRS 2002 score, PG-SGA score, and lymphocyte level (all P ​< ​0.05). ConclusionsQoL declined during RT and were associated with certain factors. Healthcare professionals should focus on alleviating treatment-related complications and identifying individuals at high risk of malnutrition early to improve outcomes for patients with NPC.

Prognostic Factors for Cardiotoxicity among Children with Cancer: Definition, Causes, and Diagnosis with Omics Technologies.

Improvements in the treatment of childhood cancer have considerably enhanced survival rates over the last decades to over 80% as of today. However, this great achievement has been accompanied by the occurrence of several early and long-term treatment-related complications major of which is cardiotoxicity. This article reviews the contemporary definition of cardiotoxicity, older and newer chemotherapeutic agents that are mainly involved in cardiotoxicity, routine process diagnoses, and methods using omics technology for early and preventive diagnosis. Chemotherapeutic agents and radiation therapies have been implicated as a cause of cardiotoxicity. In response, the area of cardio-oncology has developed into a crucial element of oncologic patient care, committed to the early diagnosis and treatment of adverse cardiac events. However, routine diagnosis and the monitoring of cardiotoxicity rely on electrocardiography and echocardiography. For the early detection of cardiotoxicity, in recent years, major studies have been conducted using biomarkers such as troponin, N-terminal pro b-natriuretic peptide, etc. Despite the refinements in diagnostics, severe limitations still exist due to the increase in the above-mentioned biomarkers only after significant cardiac damage has occurred. Lately, the research has expanded by introducing new technologies and finding new markers using the omics approach. These new markers could be used not only for early detection but also for the early prevention of cardiotoxicity. Omics science, which includes genomics, transcriptomics, proteomics, and metabolomics, offers new opportunities for biomarker discovery in cardiotoxicity and may provide an understanding of the mechanisms of cardiotoxicity beyond traditional technologies.

Prognostic impact of resting heart rate on outcomes after allogeneic hematopoietic cell transplantation

Abstract Funding Acknowledgements Type of funding sources: None. Background Allogeneic hematopoietic cell transplantation (HCT) is an effective treatment for patients with hematologic malignancies, but is associated with life-threatening toxicities which contribute to prolonged hospitalization and chronic comorbidities. The presence of life-threatening toxicities results in variable length of survival. In this context, identifying appropriate prognostic biomarkers of HCT response is of clinical importance. Pre-treatment elevated resting heart rate (RHR) has been associated with increased risk of toxicities and worse survival in patients with solid tumors, but this has not been studies in patients undergoing HCT. Purpose To examine the association between pre-HCT RHR and outcomes after allogeneic HCT. Methods This was a retrospective cohort study of patients who underwent allogeneic HCT for acute leukemia or myelodysplastic syndrome as adults (≥18 years old). RHR was obtained from pre-HCT screening electrocardiogram or echocardiogram after a 5-minute rest in the supine position. RHR was first divided into quartiles: 50-66 beat per minutes (bpm), 67-75 bpm, 76-85 bpm, 86-163 bpm. There was no significant association between RHR and 2-year mortality among the three lowest quartiles, and they were combined in our analyses (lower RHR [&amp;lt;86 bpm] vs. elevated RHR [≥86 bpm]). Outcomes of interest included length of hospitalization, major adverse cardiovascular events (MACE: myocardial infarction, coronary artery stenosis, congestive heart failure), and cause-specific (relapse, non-relapse) and all-cause mortality, at 2 years. Results There were 792 consecutive patients who underwent HCT between 2007-2014. Median age was 51 years (range 18–74 years); 53.8% were male and 57.1% were non-Hispanic white. Average length of hospitalization was significantly longer in patients with elevated RHR compared to those with lower RHR (35.6 [21.2] vs 32.0 [18.7] days; P = 0.003). However, there was no association between RHR and the development of MACE after HCT. Patients with elevated RHR had significantly worse 2-year overall survival (50.2% vs. 66.1%, p&amp;lt;0.001; Figure 1) compared to those with lower RHR. In the multivariable model (adjusted for age at HCT, sex, diagnosis, stem cell donor source, risk of relapse, HCT conditioning intensity, hypertensive medication, and hemoglobin), elevated RHR was associated with increased risk of all-cause (HR:1.41, 95% CI 1.11–1.79; P=0.005), relapse related (HR: 1.60 95% CI 1.11–2.31; P= 0.012), and non-relapse-related (HR:1.58, 95% CI 1.13–2.21; P = 0.007) mortality. Conclusion This study is the first to demonstrate the association between pre-treatment RHR and clinically important outcomes in patients with acute leukemia or myelodysplastic syndrome undergoing HCT. This information may be used to facilitate treatment decisions prior to HCT and guide interventions to decrease the risk of treatment-related complications after HCT.

Clinical features and prognosis of pediatric acute lymphocytic leukemia with JAK-STAT pathway genetic abnormalities: a case series.

The objective of this study is to explore the clinical features and outcomes of pediatric patients with acute lymphoblastic leukemia (ALL) harboring JAK-STAT signaling pathway genetic abnormalities. This retrospective case series examined the clinical data of pediatric patients diagnosed with ALL harboring JAK-STAT pathway genetic abnormality at the Children's Hospital of the Capital Institute of Pediatrics between January 2016 and January 2022. Bone marrow next-generation sequencing was used to reveal the JAK pathway abnormalities. Descriptive statistics were used. From 432 children with ALL during the study period, eight had JAK-STAT pathway genetic abnormalities. Regarding immunotyping, there were four patients with common-B cell types and one with pre-B cell type. The three patients with T-ALL had early T-cell precursor(ETP) type, pre-T cell type, and T cell type. Gene mutations were more common than fusion genes. There was no central nervous system involvement in eight patients. All patients were considered at least at intermediate risk before treatments. Four patients underwent hematopoietic stem cell transplantation (HSCT). One child had a comprehensive relapse and died. The child had a severe infection and could not tolerate high-intensity chemotherapy. Another child relapsed 2years after HSCT and died. Disease-free survival was achieved in six children. JAK-STAT pathway genetic abnormalities in pediatric Ph-like ALL are rare. Special attention should be paid to treatment-related complications, such as infection and combination therapy (chemotherapy, small molecule targeted drugs, immunotherapy, etc.) to reduce treatment-related death and improve long-term quality of life.