Journals
2025 EN
Sun Steven · Cardona Kenneth · Tseng William W.
ABSTRACT Introduction Soft tissue sarcomas are a diverse group of rare cancers, with approximately 15%–20% found in the retroperitoneum. Liposarcomas (LPS) make up approximately half of all retroperitoneal (RP) sarcomas, with most cases classified as either well‐differentiated (WD) or dedifferentiated (DD). DD LPS is more aggressive, with a higher local recurrence rate and risk of distant metastasis compared to WD LPS. The purpose of this review is to outline surgical management of RP LPS and highlight the multimodal treatment strategies for both primary and recurrent disease, along with considerations for their effective implementation. Methods The current medical literature was reviewed for studies focused on retroperitoneal liposarcoma and its treatment with surgery, radiation, and chemotherapy. The data was interpreted and compiled in the context of expert clinical experience. Results Along with histopathologic analysis, tumor biology can inform patient prognosis. Surgery, the standard treatment for RP LPS, can be either curative or palliative. In primary disease, an attempt should be made to achieve wide surgical margins when feasible. Surgery for recurrent disease requires careful timing and an understanding of the potential benefit versus risk. Neoadjuvant radiation therapy can improve local control of RP LPS; however, data supporting the use of neoadjuvant chemotherapy are currently lacking. Conclusion Multimodality treatment of RP LPS is complex and requires consideration of tumor biology and extent of disease, along with individual patient characteristics. Multidisciplinary team collaboration is critical for improving outcomes in patients with RP LPS.
Journals
2025 EN
Rami Avina · Bona Kira · Shusterman Suzanne
+6 more
ABSTRACT Background Phase 1 or phase 1/2 trials are a first step in pediatric cancer drug development. Currently, there is a paucity of information regarding contemporary outcomes for pediatric patients enrolled in these trials. We describe characteristics and outcomes of patients enrolled in pediatric phase 1 clinical trials over a 9‐year period at a single institution. Methods We queried our clinical trials management system to generate a list of patients enrolled and treated on pediatric phase 1 or phase 1/2 trials from 2011 to 2019. We collected baseline demographics, clinical data, efficacy, and safety endpoints post‐enrollment including: time to death, objective response to therapy, duration on therapy, need for dose modification, and occurrence of dose‐limiting toxicity. Overall survival was calculated using Kaplan–Meier methods. Results A total of 224 unique patients accounted for 259 enrollments and 242 treatment episodes. The median age at enrollment was 11 years (range 0–27 years) and 56.2% were male. The majority were White (85.7%) and Non‐Hispanic (88.2%). English was the primary language for 86.3% of patients, and 54.9% had private insurance. Solid tumors were the most common malignancy (41.0%), followed by brain tumors (34.1%), and hematologic malignancies (24.9%). Among treatment episodes, 49.3% received targeted monotherapy. After first enrollment, 27.6% of patients had an objective response to therapy (52.9% for hematologic malignancies, 20.5% for brain tumors, and 15.8% for solid tumors). The median duration of therapy was 1.5 months. Median overall survival from first enrollment for 218 patients treated with available vital status was 13.1 months. Toxicity outcomes included 27 patients (11.2%) requiring dose modification and 22 patients (9.0%) having a DLT. Conclusions Overall survival is poor for patients in pediatric oncology early phase trials, despite approximately a quarter having an initial response. These data are informative for discussions between providers and families regarding outcomes after phase 1 trial participation.
Journals
2025 EN
Martin Samantha D. · Robinson Eva C. · Weller Edie
+3 more
ABSTRACT Background Numerous induction therapies have been evaluated for high‐risk neuroblastoma (HRNBL). It is not known how these regimens' response rates nor toxicities compare. We aimed to describe and compare key features of HRNBL induction regimens and their associations with study‐level end‐induction response (EIR). Methods We performed a systematic review (PubMed) of prospective trials of frontline HRNBL therapy published January 1, 1995–October 31, 2024 that reported EIR. EIR was measured as partial response or better (PR+) per protocol response criteria. Results 1395 unique titles were screened, yielding 95 abstracts. Of these, 29 publications evaluating 36 induction regimens met inclusion criteria, with a median of 64.5 patients (range: 7–652) per regimen. Median cycle number was 6 (range: 2–9), cycle length was 21 days (10–28), and total duration of induction was 18 weeks (11.4–36). An alkylator and a platinum agent were used in all regimens. Only six regimens (16.7%) included a novel agent. The median study level EIR rate (PR+) was 84.4% (64.3–100), with a weighted average by the number of participants of 79.4%. Study level EIR did not vary over time. Anthracycline‐containing regimens had higher EIRs. Dose cisplatin intensity was negatively associated with EIR. The median toxic death rate was 0% (0–4.1). Conclusions Over the past 30 years, induction regimens have relied heavily on conventional chemotherapy. Despite differences in agents, doses, and duration, study‐level EIR rates have not improved over time. Future induction regimens incorporating novel agents will be crucial to improve EIR and reduce toxicities.
Journals
2025 EN
Harris Carolyn S. · Kober Kord M. · Shin Joosun
+7 more
ABSTRACT Background Inflammation is associated with sickness behavior symptoms in patients receiving chemotherapy. However, its impact on symptom burden (i.e., higher number of concurrent symptoms) requires evaluation. Study purposes were to evaluate for differentially perturbed immune and/or inflammatory pathways between outpatients receiving chemotherapy with Low (i.e., 0–8) versus High (i.e., 16–38) symptom burden and identify common immune and/or inflammatory pathways among symptom burden and single sickness behavior symptoms. Methods Prior to their second or third cycle of chemotherapy, oncology outpatients reported the occurrence of 38 symptoms using the Memorial Symptom Assessment Scale and provided a peripheral blood sample. Using previously identified symptom cutpoints, patients with Low versus High symptom burden were evaluated. Transcriptome‐wide gene expression was quantified using RNA‐sequencing ( n = 213; RNA‐seq sample) or microarray ( n = 207; microarray sample) technologies. Pathway impact analyses (PIA) were performed and signaling pathways were defined with the Kyoto Encyclopedia of Genes and Genomes database. Fisher's combined probability test was used to identify perturbed pathways between the Low and High symptom burden groups across both samples (false discovery rate < 0.005). Results For the RNA‐seq sample, 159 patients had High and 54 patients had Low symptom burden. For the microarray sample, 135 patients had High and 72 patients had Low symptom burden. Of the 40 pathways that were perturbed between the Low and High symptom burden groups, 10 were involved in immune or inflammatory processes. Cytokine–cytokine receptor interaction and endocytosis pathways were the common pathways identified across this study and PIAs of single sickness behavior symptoms. Conclusions This study is the first to identify differentially perturbed immune and inflammatory signaling pathways that were associated with symptom burden in oncology patients receiving chemotherapy. Evaluation of interventions targeted at the cytokine–cytokine receptor interaction and endocytosis pathways may decrease the burden associated with single and multiple occurring symptoms.
Journals
2025 EN
Qureshi Imran · Rella Steven · Shaukat Aasma
ABSTRACT Background Given COVID‐19's emergence as a new entity and colorectal cancer's (CRC) rising incidence in certain populations, we conducted this retrospective cohort study to determine the link between COVID‐19 and the mortality of those with CRC and how socioeconomic factors influence it. Methods Using the National Cancer Database (NCDB), we used logistic regression to get the odds ratio (OR) for delayed treatment and Cox proportional hazards modeling for each stage to get the adjusted hazard ratios (HR) of mortality. Results COVID‐19 positivity was associated with higher mortality and delayed treatment. The association of race, ethnicity, insurance, urbanization, comorbidity burden, education levels, and income varied by when the patient tested positive relative to colorectal cancer diagnosis. Conclusions This implies that vaccinations may be a part of management and that CRC patients who develop COVID‐19 infection may warrant closer follow‐up during treatment.
Journals
2025 EN
Shulman David S. · Vo Kieuhoa T. · Balis Frank M.
+11 more
ABSTRACT Background Fimepinostat, an oral dual inhibitor of histone deacetylase (HDAC) and phosphatidylinositol‐4,5‐bisphosphate 3‐kinase (PI3K), has shown activity in preclinical models of Myc‐driven pediatric malignancies. This Phase 1 trial aimed to determine the recommended pediatric Phase 2 dose (RPP2D), describe the toxicity profile, and evaluate the pharmacokinetics of fimepinostat in children with relapsed and refractory solid and central nervous system (CNS) tumors. Methods This multicenter, Phase 1 study enrolled patients ages 1–21 years with relapsed or refractory solid tumors, CNS tumors, or lymphoma. The dose‐escalation phase followed a 3 + 3 design, starting at 27.5 mg/m 2 and escalating to 45 mg/m 2 . Following dose escalation, three expansion cohorts were opened including cohorts for patients with Myc(n)‐driven neuroblastoma, Myc‐driven extracranial solid tumors, and diffuse large B‐cell lymphoma or Burkitt lymphoma. The pharmacokinetics of fimepinostat and its metabolites were studied after the first dose. Results Twenty‐six patients were enrolled, with 25 receiving treatment. The median age was 13.6 years (range: 4.1–20.9). In the dose‐escalation phase, 12 patients were evaluable for DLT assessment. The RPP2D was initially determined to be 45 mg/m 2 but was revised to 35 mg/m 2 after observing DLTs in the dose‐expansion phase. Treatment‐related adverse events were primarily hematologic and gastrointestinal. No objective responses were observed in 23 evaluable patients. Three patients had stable disease for over four cycles, including a patient with MYCN amplified neuroblastoma with stable disease for 24 cycles. Pharmacokinetic analysis showed significant interpatient variability and rapid conversion of fimepinostat to its metabolites. Conclusion Fimepinostat was tolerable at a dose of 35 mg/m 2 in children with relapsed and refractory solid and CNS tumors, but lacked significant clinical activity. Discovery of drugs to target Myc continues to be a high priority for childhood cancers. Trial Registration ClinicalTrials.gov identifier: NCT02909777
Journals
2025 EN
Harada Garrett K. · Park Jino · Peterson Nicholas
+7 more
ABSTRACT Background The relative benefit of neoadjuvant therapies remains controversial for patients with (borderline) resectable pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to create a model to predict response to multiagent neoadjuvant chemotherapy (NAC) followed by radiotherapy with elective nodal irradiation (ENI). Methods Using the National Cancer Database (NCDB), we identified patients with cT1‐4N0M0 PDAC diagnosed between 2006 and 2020 treated with multiagent NAC, radiation with ENI, followed by curative resection with nodal dissection. A LASSO logistic regression model was used to predict ypN0 status, with generation of a nomogram and assessment of outcomes in training and testing cohorts. Secondary endpoints of negative‐margin resection and overall survival were also examined. Out‐of‐sample predictions were then made on a separate ENI‐naïve cohort, with similar assessments of selected outcomes. The threshold for statistical significance was set to p < 0.05. Results A total of 1053 patients were identified with a median age of 64.0 years (IQR = 57–70 years). The final model included pancreatic body tumor location, clinical T stage, time from diagnosis to radiation therapy and surgery, ENI dose, and duration of NAC, among others. Patients predicted for treatment response were more likely to be ypN0 (71.5% vs. 29.7%, p < 0.001), had more R0 resections (87.3% vs. 62.6%, p < 0.001), and improved OS after accounting for competing risks of perioperative death (SHR = 0.64, 95% CI = 0.46–0.89, p = 0.008). A similar significant trend was noted in the ENI‐naïve cohort ( N = 1258). Model AUC was 0.718 and 0.725 in training and testing cohorts, respectively. Conclusions Using a machine learning approach, we define a nomogram capable of predicting treatment response to multiagent NAC followed by radiotherapy with or without ENI. Patients selected by this model had higher rates of ypN0, higher R0 resection rates, and improved OS.
Journals
2025 EN
Maurya Rakesh K. · Montesinos Steven · Bogomaz Mikhail
+1 more
Abstract Background Psychoeducation is an important part of mental health services offered by counsellors. This study used qualitative content analysis to explore ChatGPT, a generative artificial intelligence (AI) tool, as a resource for psychoeducation in the context of mental health. Method Researchers created carefully crafted prompts based on common psychoeducational themes provided to clients, covering seven critical areas: depression, anxiety, general health, substance abuse, religious/spiritual issues, lifestyle, routine health habits and interpersonal matters. A coding manual was developed encompassing six criteria to assess the quality of psychoeducational responses of ChatGPT: accuracy, clarity, relevance, empathy, engagement and ethical considerations. Findings The reviewers assessed ChatGPT's responses to 21 psychoeducational prompts as accurate, clear and relevant, with an empathic tone in responses to emotionally challenging queries. ChatGPT engages users by offering actionable steps and suggestions. The tool consistently demonstrated ethical considerations by advising users to consult qualified professionals when necessary. The findings suggested ChatGPT's potential as a reliable source of psychoeducation, particularly for individuals with very limited access to mental health resources. Conclusion This research underscores ChatGPT's potential as a valuable psychoeducational resource for mental health concerns while emphasising the need for ongoing assessment and user feedback to address its limitations and ensure responsible practice in the dynamic field of AI‐powered mental health support. Future studies should explore user experiences and incorporate diverse perspectives to further enhance our understanding of ChatGPT's utility in real‐world mental health contexts.
Journals
2025 EN
Captari Laura E. · Guterres Karley · Oleson Dottie
+2 more
Abstract Background Despite the recognition of meaning and hope as salient for many individuals in mental health treatment, little empirical attention has been given to patient perspectives. Research has primarily looked at the presence—or absence—of meaning and hope, and associations with symptom distress and suicidality. Aims These constructs are multi‐faceted and influenced by social, cultural and spiritual/religious contexts. Understanding where clients draw meaning and hope from can provide valuable information to inform case formulation, treatment planning and intervention. Materials and Methods This mixed method practice‐based study ( N = 233) in an outpatient community clinic (a) elucidated key areas that fuel clients' sense of meaning and hope and (b) explored associations with well‐being. Results Qualitatively, we identified six domains through thematic analysis: interpersonal, action‐based, transcendent, intrapersonal, environmental/contextual and lacking/searching. A sub‐set of clients also emerged who were lacking in and/or searching for meaning or hope. Quantitatively, one‐way ANOVA results indicated that source diversity was associated with greater well‐being. Discussion Findings illustrate that patients draw from culturally and spiritually embedded sources to construct meaning and hope in their lives, with distinctions between areas most salient for meaning, hope and both. Furthermore, having fewer sources of meaning and/or hope may represent a well‐being liability. Conclusion Therapists should pro‐actively explore and consider ways to bolster patients' sources of meaning and hope, considering evidence of implications for well‐being outcomes.
Journals
2025 EN
Crabtree Sarah A. · Captari Laura E. · Hydinger Kristen R.
+2 more
Abstract Introduction Positive psychology and virtue ethics traditions suggest that virtue development is a pathway to well‐being, but few studies have examined how psychotherapy in naturalistic settings contributes to clients' virtue engagement. Method This study was conducted at a community mental health clinic specialising in contemporary relational psychotherapy (CRP) in the northeast United States. The embedded, explanatory mixed method design included (a) longitudinal mixture‐modelling to identify clients showing gains in relational virtue engagement over time, and (b) interviewing a subsample ( N = 15) of these clients. Results Our findings suggest that virtue engagement in CRP emerges (a) within the dynamic conditions of the alliance and (b) through holistic attunement to clients' identities, experiences, mental health and growth in capacities that promote wisdom and flourishing. Clinical and research implications and future research directions are discussed.