Background Cardiac MRI plays a key role in the assessment of pulmonary regurgitation (PR) after surgical repair of tetralogy of Fallot (TOF). However, its use may be limited by low availability, claustrophobia, or incompatible pacemakers or defibrillators. Purpose To evaluate the utility of dynamic chest radiography (DCR) for estimating PR after surgical TOF repair. Materials and Methods In this retrospective observational study, patients with repaired TOF who underwent DCR and phase-contrast cardiac MRI within 1 week between February 2018 and June 2024, and age- and sex-matched healthy volunteers, were enrolled. Temporal changes in pixel values of pulmonary arteries on DCR images were analyzed using specialized software. The maximum pixel value change (Max PV), maximum slope of pixel value change (Max PV Slope), and minimum slope of pixel value change (Min PV Slope) during a single cardiac cycle were calculated. Correlation between these indexes and PR fraction (PRF) at phase-contrast MRI and the ability of each index to differentiate severe PR (>30%) from nonsevere PR (≤30%) were assessed. Pearson correlation and receiver operating characteristic analyses were performed. Results The final study sample included 58 patients with repaired TOF (mean age, 30.6 years ± 10.3 [SD]; 29 [50%] male patients) and 14 healthy volunteers (mean age, 31.1 years ± 5.5; eight [57%] male individuals). Compared with patients with nonsevere PR and volunteers, patients with severe PR had the highest mean Max PV (severe PR: 26.2% ± 8.1; nonsevere PR: 14.1% ± 4.2; volunteers: 9.4% ± 3.0; P < .001), highest mean Max PV Slope (percentage change per frame) (severe PR: 6.6 ± 2.2; nonsevere PR: 2.9 ± 0.9; volunteers: 1.8 ± 0.6; P < .001), and lowest mean Min PV Slope (percentage change per frame) (severe PR: -7.2 ± 2.0; nonsevere PR: -4.6 ± 1.6; volunteers: -3.5 ± 1.4; P < .001). For patients with repaired TOF, all indexes were correlated with PRF; of these indexes, Max PV Slope had the highest correlation (R = 0.87; P < .001) and area under the receiver operating characteristic curve (0.98 [95% CI: 0.94, 1.0]; cutoff, 4.13%), yielding a sensitivity of 93% and specificity of 94%. Conclusion Max PV Slope from DCR showed high diagnostic value for PR severity in patients with repaired TOF. © RSNA, 2026 Supplemental material is available for this article. See also the editorial by Gerstner Saucedo in this issue.
Hematological malignancies (HM) occur mostly in older patients; aging is potentially associated with loss of autonomy and cognitive impairment. However, the role, burden, and supportive needs of primary caregivers (PC) of older patients with HM have rarely been investigated. Thus, our main objective was to measure associations between the instrumental, educational, and emotional unmet needs of PCs of older patients with various HM and the quality of life (QoL) in these dyads, and, secondarily, to explore related factors. This multicenter cross-sectional study was offered to all patients over 65 years diagnosed with any HM, treated or not, having a PC, and able to fill out a self-questionnaire. Questionnaires were given to outpatients, who passed them on to their PC to fill in and return. Questionnaires assessed burden, cognition, quality of life, tasks for which help is needed, and needs from the PC's perspective. Among 104 included patients, only 59 questionnaires of dyads were analyzable. The median age of patients was 76 years and of PCs was 70 years. PCs were mainly the spouses (n = 36/59). Few PCs stated they needed support: 10% required emotional support (higher when PC had cognitive complaint, p = 0.001), 18% instrumental support (higher when patients were male, p = 0.05 or PC had cognitive complaint, p = 0.01) and 24% educational support. The median EQ-5D-5L global score was 65 in patients and 80 in PCs. The patients' self-perceived burden (SPB) had a median at 5/10 (IQR = 7). When the patient was male, the Zarit burden score was higher (p = 0.002), as well as disrupted schedule (p = 0.05), financial problems (p = 0.03), and health problems (p < 0.001), and self-esteem lower (p < 0.001) at Caregiver Reaction Assessment (CRA) sub scores. An overall cognitive complaint concerned 54.4% of patients and 33% of PCs. There was a higher proportion of cognitive complaints in male patients (70% vs 33% in females, p = 0.01), who reported a significantly higher level of responsibility in their last professions and were more likely to be under active cancer treatment. This study highlights the need to explore cognitive complaints before and during treatment and potentially provide neuropsychological assessment and educational support in these dyads.
Congenital heart defects (CHDs) are associated with disruptions in one-carbon metabolism. In a family-based trio design, we investigated whether plasma concentrations of choline, betaine, and folate are associated with CHD severity. The study included 72 children with CHD, 69 of their mothers and 64 of the fathers. CHD clinical severity was classified according to the European network of population-based registries for the epidemiological surveillance of congenital anomalies (EUROCAT) system and the German PAN study (Prevalence of Congenital Heart Defects in Newborns). Concentrations of choline, betaine, and folates were quantified in plasma and urine samples from a subgroup of the participants. The children [mean (SD) age 3.1 (3.2) years, 59.7% males] presented with varying CHD severities according to EUROCAT (62.5% severe and 37.5% mild) and PAN classifications (45.8% severe, 30.6% moderate and 23.6% mild). The means (SD) of plasma concentrations of choline were 14.0 (10.0) µmol/L in the children, 9.5 (5.1) µmol/L in the mothers and 10.3 (5.4) µmol/L in the fathers. Plasma choline concentrations < 10 µmol/L were observed in 38 mothers (66.7%) and were associated with having a child with severe CHD [adjusted odds ratio (aOR) 3.7; 95% confidence intervals (95%CIs) = 1.1, 12.2] compared to mothers with choline ≥ 10 µmol/L. Lowered plasma choline concentrations were detected in 27 fathers (62.8%) and were also associated with severe CHD (aOR 7.4; 95%CIs = 1.7, 31.5). Child concentrations of choline, betaine and folate and parents' concentrations of betaine and folate were not associated with disease severity. Lower plasma choline in the parents detectable several years after conception was related to having a child with severe CHD compared to families of children with higher plasma choline. Maternal and paternal choline metabolism may have a role in modulating CHD severity. Etiological studies aiming at the prevention of congenital anomalies should focus on maternal and paternal risk factors in the preconception and early pregnancy.
Sickle cell disease (SCD) constitutes a significant public health concern in the Kingdom of Saudi Arabia (KSA), affecting a substantial proportion of the population in the southern province of Jazan. The chronic and progressively incapacitating nature of SCD exerts a humanistic, psychological, and economic burden on the affected individuals and families. This study aims to assess this multifaceted burden on individuals with SCD in the Jazan region of KSA. We conducted a cross-sectional observational study using a self-administered validated questionnaire among SCD patients seeking medical services in various hospitals in the Jazan region. The questionnaire included sections to assess physical health, pain, social life, psychological distress, and financial burden. Descriptive statistics summarised participant characteristics. Comparative analyses using Chi-square tests and T-tests were conducted to explore differences in demographic variables between respondents reporting higher versus lower spending burdens. These analyses were intended to describe observed differences within the study sample rather than to infer population-level associations. We included 110 individuals with SCD, with a mean age of 28.43 ± 9.66 years, 55.5% male, 4.5% non-Saudi, single (62.7%), with a little less than half residing in cities. The study showed low employment rates (36.4%) and high out-of-pocket expenditures for over half the patients, with transportation being the largest expense (SAR 828.51 ± 925.84/USD 220.94 ± 246.89 per month). High spending burden was associated with poorer physical health (p < 0.001). Hydroxyurea was the most commonly used therapeutic option (81.8%), while the use of newer agents, such as L-glutamine and crizanlizumab, was limited. Psychological distress was significantly associated with age (p = 0.008) and marital status (p = 0.001), with married individuals being more distressed. Social scores (p = 0.006) were significantly lower in individuals experiencing distress, while physical health (p < 0.001) and pain scores were higher (p < 0.001). Most reported disruption in social interactions and work life, compounded by a lack of family support. Furthermore, a majority felt their physicians lacked empathy and did not discuss treatment goals, necessitating half to avoid visits due to fear. SCD patients face considerable socioeconomic, psychological, and healthcare challenges, with out-of-pocket costs disproportionately burdening lower-income families. Individuals with SCD reported psychological distress, social disruption and reduced quality of life. An apparent variability in professional and familial support was noted, which may have contributed to differences in health care utilization. Additionally, self-reported quality of physician-patient communication and perceived empathy were identified as potential influences for their care-seeking behaviour. These findings reinforce the need for a larger-scale, comprehensive evaluation to confirm them and assess the need for interventions to improve healthcare access and address the psychosocial and economic burdens associated with SCD.
Dysbiosis of gut microbiome leads to resistance to immunotherapy in various advanced solid tumors. CJRB-101 is a live biotherapeutic product consisting of a novel strain belonging to the species Leuconostoc mesenteroides. To modulate the tumor microenvironment, CJRB-101 was combined with pembrolizumab. Preclinical efficacy and mechanistic studies were performed using humanized non-small cell lung cancer (NSCLC) patient-derived xenograft (PDX) models. This is a multicenter, first-in-human, two-part, phase I, open-label study of CJRB-101 (1×1011 or 4×1011 colony forming unit (CFU)/day) plus pembrolizumab (200 mg every three weeks (Q3W)) in advanced NSCLC, melanoma, and head and neck squamous cell carcinoma in both immune checkpoint inhibitor (ICI)-naive and ICI-refractory settings. The primary endpoint was to assess the dose-limiting toxicities (DLTs), adverse events, and preliminary activity of the combination treatment. Exploratory endpoints included stool metagenomics analysis and pharmacodynamics parameters. In four PDX models, CJRB-101 with pembrolizumab demonstrated enhanced antitumor efficacy, showing a tumor growth inhibition (TGI) of 77.3% in the CJRB-101 monotherapy group and 61.9% in the combination group, which was significantly improved compared with pembrolizumab alone. A distinct M2-to-M1 repolarization was observed and validated in vitro. Notably, increased activation of cytotoxic T cells was observed, suggesting an immune-mediated antitumor mechanism of CJRB-101. A total of 42 patients were enrolled in the low-dose cohort (one capsule once a day; n=6) and high-dose cohort (two capsules two times a day, n=36). Metastatic NSCLC accounted for 86% (n=36) and 67% (n=28) of the patients were refractory to ICIs. None of the patients experienced DLT. In ICI-naïve NSCLC (n=12) with programmed death-ligand 1 (PD-L1) >50%, the overall response rate (ORR) and disease control rate (DCR) were 58% and 75%, respectively. The ORR was 5% and DCR was 41% in the ICI-refractory NSCLC (n=22) with an ORR of 5% and DCR of 41%. After a median follow-up of 15.6 months and 8.9 months for ICI-naïve and ICI-refractory NSCLC, the median progression-free survival was 9 months (95% CI 5.6 to not reached) and 1.8 months (95% CI 1.6 to 4.3), respectively. CJRB-101 plus pembrolizumab was well-tolerated, and none of the patients experienced grade >3 treatment-related adverse events. Early clinical data show encouraging antitumor response of CJRB-101 plus pembrolizumab in ICI-naïve metastatic NSCLC with PD-L1 >50%. NCT05877430.
Mast cell (MC) activation (MCA) disorders (MCAD) include diseases in which MCs excessively release mediators leading to recurrent manifestations of MCA. MCAD encompasses MCA syndrome (MCAS) which is defined by (i) documented systemic symptoms of MCA, (ii) a 20% increase in serum tryptase level from the individual's baseline plus 2 ng/mL and (iii) a symptom response to MC-stabilizing drugs. MCAD not fulfilling mastocytosis or all MCAS criteria are referred to as MCAD not otherwise specified (MCAD-NOS). The aim was to describe the clinical, laboratory characteristics and outcomes of the first pediatric-onset non-mastocytosis MCAD cohort. All children with the criteria of non-mastocytosis MCAD managed at the French National Referral Center for MCAD were included. Clinical, laboratory data, and outcomes were recorded. Forty-four MCAD patients (mean age at onset: 4.3 years) were identified including 36 MCAD-NOS and 8 idiopathic MCAS. Hereditary-α-tryptasemia was identified in 5/33 (15.2%) patients. The spectrum of symptoms concerned most frequently both the skin (100% of children, with urticaria, angioedema, pruritus, and/or flushing) and the gastrointestinal tract (93% patients). We identified two clinical profiles, according to the age at onset. Before 3 years of age, MCAD was associated with persistent gastrointestinal symptoms triggered by various foods (leading to a drastically limited diet), and after 3 years of age with episodic, recurrent, idiopathic, anaphylactic reactions. The administration of H1 and/or H2 antihistamines drugs +/- a leukotriene receptor antagonist resulted in a marked reduction in symptoms. The description of the clinical profiles of pediatric-onset non-mastocytosis MCAD may help to avoid diagnostic delay.
One of the key challenges in cancer treatment and precision oncology is the use of multi-omics data and their integration into matched clinical information. Although several analytical portals have been developed, most platforms do not support user-uploaded data or the integrated analysis of clinical and multi-omics datasets. To address these limitations, we developed the Korea Cancer Omics Research (K-CORE) portal, a user-friendly analytical platform designed to integrate and analyze multi-omics and clinical data. K-CORE supports various omics levels and a wide range of analytical tools. To validate the utility and reproducibility of the K-CORE, we designed synthetic datasets that reflected real-world omics data distributions. The analytical results from K-CORE were compared side by side with those from widely used R packages such as maftools and edgeR. In conclusion, K-CORE offers a practical and intuitive platform for the multidomain integration of clinical and omics data, supporting the advancement of precision oncology. Nevertheless, as analytical technologies and precision oncology continue to evolve, continuous maintenance and user feedback will become essential for future platform improvements.
As improvements in anti-cancer treatments have extended survival, patients with advanced cancer and their family caregivers face existential tension between engaging in life and coping with uncertainty about illness trajectory and the course of treatment. For a subgroup, this tension is associated with overwhelming fear and existential distress. Such adjustment difficulties may increase the risk of mental disorders, poor quality of life, and suicidality, and impair prognostic awareness and patient-clinician communication. Despite growing interest in open conversations about end-of-life issues, systematic evidence on effective psychotherapies to best support psychological adaptation in patients with high levels of existential distress is still scarce. We aim to evaluate the effectiveness of a short-term psychodynamic therapy (ORPHYS) to mitigate existential distress compared to usual psycho-oncological treatment (TAU). We conduct a two-arm parallel randomized controlled trial with an active control group. ORPHYS is a manualized individual face-to-face psychotherapy focusing on emotional and relational conflicts specific to cancer patients' illness situation. Treatment lasts between 5 and 11 months with 15 to 31 weekly sessions (50 min). TAU includes at least one individual session provided by physicians or psychologists with experience in psycho-oncological care. Patients will be assessed pre-intervention and 3, 6, 9, and 12 months after baseline. Target sample size is 160 randomized participants. We recruit patients with stage III/IV solid tumors or advanced hematological cancer and clinically significant existential distress from psycho-oncology clinics and referring oncologists at Hamburg, Düsseldorf, and Würzburg Comprehensive Cancer Centers, Germany. The primary outcome is demoralization (Demoralization Scale-II). Secondary outcomes include diagnoses of affective, anxiety and stress-related disorders, death anxiety, dignity-related distress, and quality of life. Outcome assessments are conducted via self-report questionnaires and diagnostic interviews. Linear mixed models examine outcome differences between trial arms. A confirmatory test of the group contrast at 6-month follow-up after baseline is conducted. Due to an aging population and prolonged survival, there is a growing demand to help patients deal with existential challenges undergoing palliative cancer care. The study will contribute to knowledge about how clinicians can best help patients with advanced cancer who substantially struggle with uncertainty at the end of life. German Clinical Trials Registry, DRKS00038173. Registered October 20th, 2025, https://drks.de/search/en/trial/DRKS00038173 . gov, NCT07312760. Registered December 30, 2025, https://clinicaltrials.gov/study/NCT07312760 .
Malignant serous effusions (MSEs), including pleural, pericardial, and peritoneal effusions, are common in advanced lung adenocarcinoma (LUAD). However, integrated clinicopathologic, molecular, treatment, and outcome data across effusion sites remain incompletely defined. This study retrospectively analyzed 120 cytology-confirmed LUAD-associated MSE cases from a single academic center by integrating gross fluid features, cytopathology, immunohistochemistry, targeted next-generation sequencing (NGS), systemic therapy, and clinical outcomes, including survival from first malignant effusion (SME) and overall survival (OS). Effusions were pleural (85 of 120; 70.8%), pericardial (28 of 120; 23.3%), and peritoneal (7 of 120; 5.8%). Median SME was 3.8 months, and was shortest in the small peritoneal effusion subgroup (1.0 months). OS differed by site, with pericardial involvement showing the shortest OS (6.1 months). Thyroid transcription factor 1 (TTF-1) was positive in 72.5% of cases. Programmed death ligand 1 (PD-L1) testing (n = 85) showed a tumor proportion score (TPS) of ≥1% in 80% of cases and TPS of ≥50% in 36.5% of cases. Molecular profiling was completed in 111 of 120 cases (92.5%) by identifying TP53 mutations in 47 of 111 (42.3%) and actionable driver alterations in 42.3% of cases, most commonly involving EGFR, KRAS, BRAF, ALK, and ROS1. TTF-1 positivity was associated with higher rates of actionable driver alterations and higher PD-L1 expression. PD-L1 negativity, TTF-1 negativity, and an absence of actionable driver alterations were associated with shorter SME and OS. Dual TTF-1/PD-L1 negativity defined the poorest risk subgroup (median SME, 1.2 months; median OS, 1.4 months). Multivariable analysis confirmed that TTF-1 negativity and a lack of actionable drivers remained independently adverse. Among treated patients, immunotherapy-based regimens were associated with the longest SME (6.7 months), whereas tyrosine kinase inhibitor-based therapy was associated with the longest OS (26.0 months). Integration of cytology, immunophenotype, genomics, and treatment delineates distinct prognostic subsets in LUAD with MSE. The absence of actionable driver alterations and TTF-1 negativity remains an independent adverse prognostic factor, with dual TTF-1/PD-L1-negative MSE showing particularly poor SME and OS.
To explore how nurses comfort pediatric hematology-oncology (PHO) patients, examine nurses' confidence and educational preparation in providing comfort, and inform recommendations for enhancing new nurses' readiness. Seventeen PHO nurses in the southeastern United States were recruited through professional networks and PHO-focused organizations to complete an anonymous online survey. PHO nurses completed a survey with 12 closed and 4 open-ended questions. Open-coding content analysis was used to derive themes about how nurses comfort PHO patients. Demographic data were analyzed using descriptive statistics. A conceptual model described how nurses comfort PHO patients through dynamic individualized care using the approaches of preparation, comforting presence, listening, and distraction. More experienced nurses appeared to be more likely to identify listening as a comforting approach. Nurses who were more confident using comfort approaches appeared to be more likely to use them. Comfort care is a particular priority when caring for a PHO patient. Understanding nurses' readiness to provide comfort and how they approach this key aspect of PHO care strengthens patient care and nursing practice transitions. There are opportunities to increase education and readiness for this nursing role.
Objective: To explore the clinical characteristics and prognostic significance of myelodysplastic neoplasms (MDS) with biallelic TET2 inactivation (bi-TET2) . Methods: Clinical data from 1 730 newly diagnosed de novo MDS patients treated at Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College between August 2016 and June 2025, with next-generation sequencing data, were retrospectively collected. The clinical characteristics and prognosis of patients with biallelic TET2 inactivation were analyzed. Results: Thirty-nine patients (2.3% ) harbored bi-TET2, including two with copy-neutral loss of heterozygosity on chromosome 4q24. Compared with patients with monoallelic TET2 mutations (n=147) and those without TET2 mutations (n=1 544), patients with bi-TET2 carried more gene mutations overall [4 (IQR: 3, 6) vs 4 (IQR: 2, 5) vs 2 (IQR: 1, 4), P<0.001] and had higher frequencies of mutations in ASXL1 (38.5% vs 29.9% vs 20.5%, P=0.001), SRSF2 (28.2% vs 12.9% vs 4.5%, P<0.001), SF3B1 (25.6% vs 18.4% vs 11.7%, P=0.004), EZH2 (18.0% vs 7.5% vs 4.5%, P=0.002), CUX1 (12.8% vs 3.4% vs 1.4%, P<0.001), KRAS (10.3% vs 4.3% vs 2.1%, P=0.006), CBL (10.3% vs 3.4% vs 2.6%, P=0.030), ZRSR2 (10.3% vs 6.1% vs 3.2%, P=0.017), and CEBPA (7.7% vs 1.4% vs 1.2%, P=0.019). Patients with bi-TET2 were older at diagnosis [65 (IQR: 58, 69) vs 61 (IQR: 50, 67) vs 55 (IQR: 44, 64) years, P<0.001] and had a higher proportion of normal karyotype (69.2% vs 46.3% vs 44.8%, P=0.024). Patients with bi-TET2 had a significantly shorter median overall survival (OS) time than patients with monoallelic TET2 mutations and those without TET2 mutations [18.5 (95% CI: 13.1-25.0) vs 40.6 (95% CI: 22.8-60.9) vs 54.7 (95% CI: 47.1-69.4) months, P=0.009]. Stratified analysis by IPSS-M prognostic risk categories showed that, in the high-risk group (moderate high-risk, high-risk, and very high-risk), patients with bi-TET2 had a significantly shorter median OS time[12.4 (95% CI: 8.4-NA) months] than patients with monoallelic TET2 mutations [19.7 (95% CI: 14.9-39.9) months] and those without TET2 mutations [32.0 (95% CI: 27.6-37.4) months, P<0.001]. In contrast, no significant difference in OS was observed in the low-risk group (very low-risk, low-risk, and moderate low-risk) . Conclusion: Patients with MDS harboring biallelic TET2 inactivation exhibit distinct clinical and molecular characteristics and in patients with relatively high IPSS-M risk, their prognosis is worse than that of patients with monoallelic TET2 mutations. 目的： 探究伴TET2双等位基因失活的骨髓增生异常肿瘤（MDS）患者的临床特征及预后意义。 方法： 收集2016年8月至2025年6月就诊于中国医学科学院血液病医院且有二代基因测序数据的1 730例初诊原发MDS患者的病例资料，回顾性分析伴TET2双等位基因失活患者的临床特征及预后。 结果： 39例（2.3%）患者伴TET2双等位基因失活，其中有2例检出染色体4q24位点拷贝数中性杂合性缺失。与TET2单等位基因突变患者（147例）和无TET2基因突变患者（1 544例）相比，TET2双等位基因失活患者携带的基因突变更多[4（IQR：3，6）个对4（IQR：2，5）个对2（IQR：1，4）个，P<0.001]，合并ASXL1（38.5%对29.9%对20.5%，P＝0.001）、SRSF2（28.2%对12.9%对4.5%，P<0.001）、SF3B1（25.6%对18.4%对11.7%，P＝0.004）、EZH2（18.0%对7.5%对4.5%，P＝0.002）、CUX1（12.8%对3.4%对1.4%，P<0.001）、KRAS（10.3%对4.3%对2.1%，P＝0.006）、CBL（10.3%对3.4%对2.6%，P＝0.030）、ZRSR2（10.3%对6.1%对3.2%，P＝0.017）、CEBPA（7.7%对1.4%对1.2%，P＝0.019）基因突变比例更高，中位发病年龄更高[65（IQR：58，69）岁对61（IQR：50，67）岁对55（IQR：44，64）岁，P<0.001]，正常染色体核型比例也更高（69.2%对46.3%对44.8%，P＝0.024）。生存分析显示，伴TET2双等位基因失活患者中位总生存（OS）期为18.5（95% CI：13.1~25.0）个月，较TET2单等位基因突变患者[40.6（95% CI：22.8~60.9）个月]和无TET2基因突变患者[54.7（95% CI：47.1~69.4）个月，P＝0.009]明显缩短。进一步按分子国际预后评分系统（IPSS-M）预后风险分层分析发现，在IPSS-M相对高危（IPSS-M较高危、高危、极高危）患者中，TET2双等位基因失活患者中位OS期为12.4（95% CI：8.4~NA）个月，显著短于TET2单等位基因突变患者[19.7（95% CI：14.9~39.9）个月]及无TET2基因突变患者[32.0（95% CI：27.6~37.4）个月，P<0.001]；而在IPSS-M相对低危（IPSS-M极低危、低危、较低危）患者中未观察到显著差异。 结论： 伴TET2双等位基因失活的MDS患者具有特定的临床和分子学特征，在IPSS-M相对高危患者中预后较TET2单等位基因突变患者更差。.
Background: Head and neck cancer (HNC) and its multimodal treatment substantially impair speech, swallowing, breathing, appearance, and psychosocial well-being. Patient-reported outcome measures (PROMs) improve symptom monitoring and quality of life in oncology, yet their integration into routine HNC care remains inconsistent. This study assessed patterns of PROM use, perceived value, and barriers to implementation among healthcare professionals (HCPs) involved in HNC care. Methods: A 30-item cross-sectional survey was distributed to HCPs treating HNC patients between June 2024 and April 2025. The questionnaire explored PROM use in clinical practice and trials, perceived relevance across care phases, and implementation barriers. Respondents were classified as non-users, occasional users, or regular users. Data were analyzed descriptively with comparisons between groups. Results: Among 133 respondents, 33.8% were non-users, 29.3% occasional users, and 36.8% regular users of PROMs. Users reported inviting half of patients to complete PROMs, predominantly via paper-based questionnaires (67.8%). PROMs were mainly applied during active treatment and early follow-up to monitor symptoms, overall health, and emotional well-being, and were less frequently used to guide treatment decisions. The EORTC QLQ-C30 and HNC-specific tools were most commonly reported. Compared with users, non-users more often cited lack of time, limited training in interpreting PROM data, insufficient institutional support, resource constraints, and lack of appropriate instruments (all p < 0.05). PROM use in clinical trials was associated with routine use (p < 0.001). Conclusions: Although PROMs are widely valued in HNC care, their integration into clinical decision-making remains limited. Addressing organizational, educational, and digital barriers is essential to support sustainable implementation.
Dyspnea is a common and distressing symptom in patients with cancer, particularly in advanced stages and lung cancer. It is associated with poor quality of life and is often challenging to manage. The Respiratory Distress Observation Scale (RDOS) is a validated tool for assessing dyspnea in noncommunicative patients. To assess the validity of the RDOS by comparing it with patient-reported dyspnea using the revised Edmonton Symptom Assessment System (ESAS-r) in patients with cancer receiving palliative care (PC), and to explore associations with functional status. Observational, cross-sectional study. The study was conducted at the National Cancer Institute (INCan) in Mexico City from October 2022 to February 2023. A total of 194 adult cancer patients with dyspnea receiving PC were included. RDOS, ESAS-r, and Karnofsky Performance Status (KPS) scores were assessed. Analyses included Spearman's correlation and comparisons across KPS groups. Median RDOS score was 5 (interquartile range 3-9), with 36.1% experiencing severe dyspnea. Higher RDOS scores were observed in patients with KPS ≤40. RDOS scores correlated significantly with ESAS-r dyspnea, insomnia, and drowsiness. Agreement between RDOS and ESAS-r was higher in moderate/severe cases (79.08%) than in none/mild (63.41%). Notably, 36.59% of patients rated as mild by ESAS-r were classified as moderate/severe by RDOS. RDOS is a valuable tool for detecting respiratory distress in cancer patients unable to self-report. Early identification and comprehensive management of dyspnea are crucial, particularly in patients with compromised functional status, or advanced disease, and those vulnerable to undetection because of inability to self-report distress.
Large extracellular vesicles (large EV) released from tumor and benign cells are detectable in blood and hold potential as non-invasive biomarkers. While their diagnostic relevance has been shown in several malignancies, their role in head and neck squamous cell carcinoma (HNSCC) remains insufficiently characterized. Large EV were isolated from peripheral blood of patients with HNSCC (n = 66), non-small cell lung cancer (NSCLC; n = 52; adenocarcinoma n = 39, squamous cell carcinoma (SQCCL) n = 11), and healthy controls (n = 11) by differential centrifugation. Flow cytometry quantified surface expression of EGFR, EPCAM, MUC1, and PD-L1. Associations with clinical parameters were analyzed using t-tests, Spearman correlations, logistic regression, and random forest modeling. HNSCC-derived large EV showed significantly higher EGFR and MUC1, but lower EPCAM expression compared to controls. PD-L1 expression increased with advancing tumor stage and was positively associated with metastatic status, whereas EGFR levels declined in metastatic disease. Combined ROC analysis of EGFR, EPCAM, and PD-L1 yielded an AUC of 0.785 (p = 0.003), distinguishing HNSCC from controls. Comparative profiling revealed higher EGFR and EPCAM expression in HNSCC versus NSCLC, while MUC1 predominated in NSCLC, particularly in SQCCL; notably, the NSCLC cohort was predominantly adenocarcinoma. A marker panel comprising EGFR, EPCAM, and MUC1 differentiated HNSCC from SQCCL in this limited subgroup (n = 11) with 96.97% sensitivity, 45.45% specificity, 92.75% positive predictive value and 75.00% negative predictive value. Flow-cytometric profiling of circulating large EV provides a feasible liquid biopsy approach for tumor characterization in HNSCC. PD-L1 expression reflects tumor burden, and combined large EV marker analysis enables differentiation between HNSCC and primary squamous lung carcinoma, supporting its diagnostic utility in clinical oncology.
Early detection is critical for lung cancer patients. One lung cancer detection method under study is using sniffer dogs. This study aimed to evaluate, retrospectively, the sensitivity and specificity of theCancerDetectionDogCollective (CDDC®) method under training conditions. A team of five trained sniffer dogs analyzed breath samples from lung cancer patients and cancer-free volunteers, and a cancer sample is positive if at least three dogs indicate it. Dog handlers and experimental observers were blinded to sample identity, and detection accuracy was assessed. Primary endpoint was sensitivity, and specificity and confounding factors were also assessed. Samples were collected in 2024 from 824 volunteers, including 111 with a confirmed diagnosis of lung cancer (mean age 60, range 34-80, 18% early-stage cancer, 46% not yet oncological treated). A total of 11 900 breath samples were tested with 125 test runs per dog. Each of the five dogs demonstrated a detection performance with a sensitivity between 82% and 89%, a specificity over 95%, and an accuracy over 94%. The CDDC® dog team's corporate decision revealed a sensitivity of at least 95.5%. The cancer-free volunteers were primarily young, healthy individuals. According to the CDDC® decision rules, none of these control samples were identified as false positives by more than two dogs. Analysis of potential confounding factors revealed that weather conditions and supervisor skills were associated with the dogs' performance. The CDDC® method showed high consistency in training scenarios. Further studies should evaluate this method in a controlled clinical study alongside lung cancer screening.
Triplets incorporating proteasome inhibitors, immunomodulatory drugs, and dexamethasone are active regimens for patients with relapsed/refractory multiple myeloma (RRMM). All-oral regimens may offer greater real-world feasibility and convenience than other options. This phase I/II dose-escalation and expansion study evaluated the oral proteasome inhibitor ixazomib at a dose of 3 or 4 mg on a twice-weekly schedule (days 1, 4, 8, and 11) in 21-day cycles, plus pomalidomide at a dose of 2, 3, or 4 mg (days 1-14) and dexamethasone 12 or 8 mg (days of/after ixazomib), in 50 patients with RRMM. Patients had received a median of 2 prior lines, with 98.0% and 88.0% having received prior lenalidomide and bortezomib, respectively. The highest dose level investigated (ixazomib 4 mg, pomalidomide 4 mg) was the recommended phase II dose (RP2D). Patients received a median of 11 cycles. Common toxicities were neutropenia (76.0%; grade 3/4 22.0%/4.0%), thrombocytopenia (70.0%; 8.0%/8.0%), leukopenia (68.0%; 22.0%/0%), fatigue (52.0%; 4.0%/0%), and anemia (46.0%; 2.0%/0%). During dose escalation, two dose-limiting toxicities (grade 3 upper respiratory tract infection; grade 3 neutropenia) were reported. The overall response rate was 60.0% (24.0% ≥very good partial response [VGPR]) in all 50 patients and 65.8% (28.9% ≥VGPR) in the 38 patients who received the RP2D; the median duration of response was 18.0 and 19.3 months, median progression-free survival was 13.9 and 17.8 months, and 3-year overall survival rates were 85.2% and 80.3%, respectively. Twice-weekly ixazomib plus pomalidomide-dexamethasone is a well-tolerated, efficacious all-oral regimen with real-world utility in RRMM.
Glofitamab and epcoritamab are CD3xCD20 bispecific antibodies licensed for relapsed/refractory large B cell lymphoma (RR LBCL), yet real-world data are limited. Data were collected from 332 patients (219 glofitamab, 113 epcoritamab) across 34 UK centres (November 2023-May 2025). This high-risk cohort had median 2 prior lines of treatment; 179 (55%) primary refractory disease; 81 (25%) ECOG ≥2; 152 (50%) prior Chimeric Antigen Receptor T-cell therapy; and 232 (78%) pivotal-trial ineligible. 7 patients died before treatment initiation, 1 patient was yet to start treatment, of 324 treated patients, 28% had cytokine release syndrome (CRS), predominately grade 1/2 (82/90). Overall response rate (ORR) and complete response rate (CRR) were 43% and 24%, respectively, while for trialeligible patients the CRR was 43%. At a median 10.0 months follow-up (IQR 5.3-15.0), median progression-free survival (PFS) was 3.1 months (95% confidence interval [CI], 2.5-4.2), median overall survival (OS) was 6.9 months (95% CI, 4.9-10.8). For patients not completing cycle 2, 6-month OS was 4% (95% CI 1-11%). Median duration of complete response was not reached. Refractoriness to prior line of treatment (HR 2.89, 95% CI 1.73-4.81, p=0.007), elevated LDH (HR 2.62, 95% CI 1.74-3.93. p=0.001), bendamustine exposure within 6 months (HR 1.62, 95% CI 1.14-2.30, p=0.007) and ECOG 1 (HR 2.70, 95% CI 1.52-4.79, p=0.001) or 2 (HR 6.49, 95% CI 3.47-12.01, p.
Cancer care in conflict-affected settings represents a growing yet underrecognized global health crisis, disproportionately affecting populations in low- and middle-income countries, particularly in Africa. With over 130 million people forcibly displaced worldwide, conflict-driven disruptions to health systems have created profound gaps across the cancer care continuum, from prevention and diagnosis to treatment and palliative care. In these settings, cancer is often deprioritized in favor of acute and communicable diseases, resulting in delayed diagnosis, treatment interruptions, and poor outcomes. This review examines the impact of conflict on cancer care delivery, highlighting structural disruptions, including infrastructure destruction, workforce displacement, and supply chain collapse. Drawing on case studies from Sudan, Somalia, Burkina Faso, and Kenya, it presents exploratory, field-informed strategies to sustain care. In Sudan, telehealth, primarily through WhatsApp and mobile communication, has enabled continuity of care, real-time triage, and cross-border clinical collaboration despite severe connectivity challenges, supported by emerging hybrid digital platforms. In Burkina Faso, the collapse of surgical oncology capacity has led to predominantly late-stage, palliative interventions; however, adaptive responses such as mobile clinics, tele-oncology, and decentralized service delivery have partially mitigated these gaps. The manuscript further emphasizes the potential role of mobile oncology units in delivering cancer medicines, basic surgical care, and palliative services, alongside context-adapted training for health care workers in crisis settings. It highlights the need for coordinated safe cross-border referral systems, interoperable digital health platforms, and the establishment of safe humanitarian corridors for patient transfer. Addressing cancer care in conflict settings requires integrating oncology into humanitarian responses, strengthening decentralized and resilient systems, and fostering regional collaboration to ensure equitable access for vulnerable populations.
Childhood cancer survivors are at high risk for treatment-related chronic health conditions. How much of this risk can be attributed to lifestyle is not known. In this study, we assess associations between lifestyle and a range of chronic health conditions and estimate lifestyle-specific population attributable fractions for chronic health conditions in survivors and compare them to those of radiotherapy and chemotherapy. Here we show that unhealthy lifestyle is associated with higher risk for subsequent hypertension, dyslipidemia, diabetes, heart attack, heart failure, valvular disease, joint replacement, anxiety, depression, and impaired physical and mental quality of life. Disease proportions attributed to unhealthy lifestyle exceed those of chemotherapy and radiotherapy for hypertension, diabetes, joint replacement, anxiety, depression, and impaired physical and mental quality of life. Unlike previous cancer treatment exposures, lifestyle can be modified. We need to further develop and implement effective lifestyle interventions in childhood cancer survivors, promoting healthy weight and physical activity.
Pancreatic adenocarcinoma remains highly lethal. How modern chemotherapy reshapes the full mortality profile, including competing non‑cancer deaths, is incompletely defined. Using Surveillance, Epidemiology, and End Results (2010-2021), we identified 9624 adults (20-89 years) with primary pancreatic adenocarcinoma who received systemic chemotherapy. Cause of death (International Classification of Diseases, Tenth Revision) was classified as pancreatic cancer, other cancers, or non‑cancer causes. Stage-stratified analyses characterized mortality heterogeneity. Standardized mortality ratios (SMRs) versus the general US population were calculated in SEER*Stat; multivariable Poisson regression assessed risk factors. Temporal patterns were examined across ≤1 year, 1 to 5 years, and >5 years from diagnosis. Over a median follow-up of 14.2 months, 8218 deaths occurred. Pancreatic cancer accounted for 90.6% (n = 7448); non‑cancer causes accounted for 6.1% (n = 498), and other cancers accounted for 3.3% (n = 272). Non-cancer mortality comprised 7.8% of stage I/II deaths versus 5.1% in stage III/IV, reflecting longer survival enabling competing risks. Overall, non‑cancer mortality was markedly elevated (SMR 15.38, 95% confidence interval: 14.06-16.79), peaking in year 1 (SMR 96.10) and declining thereafter (1-5 years, SMR 13.63; >5 years, SMR 3.19). Cardiovascular deaths carried the greatest non‑cancer burden (heart disease SMR 9.96; cerebrovascular disease SMR 12.7). Infectious causes showed the highest relative risks (septicemia SMR 20.3; pneumonia/influenza SMR 88.69), concentrated in the first year. Chronic obstructive pulmonary disease (SMR 17.57) and diabetes (SMR 19.3) were additional contributors. Older patients (70-89 years) experienced the steepest early mortality. Suicide risk was strikingly increased (SMR 113.68), underscoring substantial psychological distress. In chemotherapy‑treated pancreatic cancer, non‑cancer mortality is substantial, time‑dependent, and dominated by cardiovascular and infectious causes in the first year after diagnosis. These data support integrated cardio‑oncology pathways, aggressive infection prevention, metabolic and pulmonary co‑management, and early psychosocial interventions to reduce preventable deaths and improve outcomes.