Risk Of Relapse Research Articles

Complexity in the interpretation and application of multiple guidelines for thyroid nodules: the need for coordinated recommendations for "small" lesions.

Multiple guidelines for thyroid nodule management have been developed by endocrinologists, often in collaboration with surgeons and radiologists. While there is now a lot of scientific information available to meet the needs of healthcare providers, there is not always uniformity and standardization among recommendations. Consequently, the interpretation and application of guidelines in clinical practice remain somewhat limited. In this context, the management of "small" thyroid nodule warrants full discussion. Looking at treatment guidelines, surgery is the first-line option and the risk of cancer relapse can be assessed only after at least thyroidectomy; in addition, according to guidelines of minimally invasive treatment, thermal ablation may be considered for patients with small classical papillary carcinoma. However, the Thyroid Imaging Reporting AndData Systems do not recommend biopsy in nodules less than 1cm; and performing biopsy may yield a result that is suspicious or consistent with malignancy without specifying the cancer subtype. With these premises, facingcases of "small" nodule less than 1cm is challenging. Even if the recommendations of guidelines sound singularly appropriate, they may seem conflicting. Coordinated guidelines are needed.

Effect of an Internet-Based Pilates Telerehabilitation Intervention in People With Multiple Sclerosis: Protocol for a Randomized Controlled Trial.

Physical activity (PA) has been recommended in multiple sclerosis (MS) to maintain good physical fitness and mental health, reduce the severity of symptoms and risk of relapse, and improve quality of life. Pilates has been suggested as an ideal PA to manage physical, cognitive, and psychological symptoms of MS and a useful method to maintain and improve balance and gait. This paper presents the protocol for a study that aims to evaluate the efficacy on the physical domain (specifically balance and gait) of a home-based, self-managed PA intervention delivered through the MS-FIT exergame (HELAGLOBE Società a responsabilità limitata). In addition, measures of cognitive performance, quality of life, and well-being will be considered. This is a 2-arm, multicenter, randomized controlled trial with 3 assessment points (baseline, 12 weeks postintervention, and 6 weeks follow-up). People with MS with mild disability, low risk of falling, preserved cognitive functions, and low anxiety and depression are potential eligible participants. The experimental group (MS-FIT) will self-administer the MS-FIT exergame at home in addition to their leisure-time physical activities. MS-FIT is an internet- and Pilates-based tool that uses the Microsoft Kinect Sensor V2. Participants in the control group will only have access to their leisure-time physical activities. Participants in the MS-FIT group will train at home with MS-FIT for 12 weeks and will be required to perform the exercises for a total of 30 minutes/day for at least 3 days/week. The primary outcome is the Timed Up and Go, a test designed to assess walking. We will also administer additional tests for motor function (visual analog scale 0-10, Timed 25-Foot Walk, Ambulation Index, 2-minute walk test, Twelve Item Multiple Sclerosis Walking Scale, Nine-Hole Peg Test), cognition (Brief International Cognitive Assessment for Multiple Sclerosis), fatigue (Modified Fatigue Impact Scale), quality of life (Multiple Sclerosis Quality of Life-54), well-being (Psychological Well-Being Scales), and PA (International Physical Activity Questionnaire and Minnesota Leisure Time Physical Activity Questionnaire). Acceptance and satisfaction with the intervention received (Client Satisfaction Questionnaire and an adapted version of the Tele-healthcare Satisfaction Questionnaire - Wearable Technology) and subjective impressions of changes in performance (Patients' Global Impression of Change) will also be assessed. Recruitment for the trial started on March 16, 2022, and the first participant was randomized the same day. Data analysis and results are expected to be published in 2025. Pilates has proven beneficial in several neurological diseases such as MS. With this study, we will provide evidence for the use in clinical practice of a digital tool for self-administered Pilates exercises at home as a complement to rehabilitation and for the continuity of care in MS. ClinicalTrials.gov NCT04011579; https://tinyurl.com/2p9n4d2t. DERR1-10.2196/58026.

Analysis of prognostic factors and establishment of a recurrence risk prediction model for papillary thyroid carcinoma based on BRAF stratification.

Predicting the likelihood of papillary thyroid carcinoma (PTC) recurrence is crucial for improving patient outcomes. The association between the BRAF V600E (BRAF) mutation and PTC recurrence remains controversial. Our goal was to determine prognostic features of PTC patients and construct models for predicting recurrence risk according to BRAF mutation status. A total of 811 PTC patients whose clinical information and survival data were available were included in this study. Independent prognostic variables of PTC identified by screening via LASSO-Cox regression analysis were then used to construct nomograms. The performance of the predictive models was assessed according to the C-index, ROC curve, validation curve, and decision curve analyses. Kaplan-Meier curves were used to analyze differences between patients grouped according to prognostic factors and relapse risk. Multivariate Cox regression analysis demonstrated that extrathyroidal extension (ETE), vascular tumor thrombus, and lymph node yield (LNY) were correlated with recurrence-free survival (RFS) in the BRAF mutation-negative group, while extranodal extension (ENE), number of metastatic lymph node (NMLN), pathological stage, and vascular tumor thrombus were correlated with RFS in the BRAF mutation-positive group. The mutation-stratified predictive models demonstrated better performance than the model without stratification, as indicated by the greater C-index values (0.880 vs. 0.859 vs. 0.753), AUC values (1-year AUC: 0.946 vs. 0.947 vs. 0.758; 3-year AUC: 0.889 vs. 0.871 vs. 0.760; 5-year AUC: 0.845 vs. 0.793 vs. 0.758), and net clinical benefit. The calibration curves at 1 year, 3 years, and 5 years showed good consistency. The bootstrap internal validation had good AUC values exceeding 0.8 and showed a well-fitting calibration curve. Significant differences in RFS were observed between the low-risk and high-risk groups (P < 0.001). Stratifying patients based on their BRAF mutation status can facilitate the development of better and more targeted postoperative management strategies. Nomograms for BRAF mutation positive and negative patients were developed to precisely and consistently predict recurrence risk in PTC patients.

Genotype 3 is linked to worse liver disease progression in hepatitis C patients even after SVR following DAA therapy

Background and aimsHCV genotype (GT) 3 is associated with rapid liver disease progression. However, the liver disease progression and its risk factors in patients with HCV GT 3 infection after sustained virological response (SVR) following direct-acting antivirals (DAAs) remain unclear. Therefore, we aimed to investigate the liver disease progression of patients with GT 3 after SVR.MethodsThis was a retrospective cohort study of patients with HCV infection who achieved SVR by DAAs. The clinical outcome was overall liver disease progression (OLDP), defined as newly diagnosed compensated liver cirrhosis, decompensated liver cirrhosis, or hepatocellular carcinoma. The incidence of OLDP was evaluated by Kaplan−Meier analysis. Cox regression analysis identified the risk factors for OLDP.ResultsA total of 409 patients (46.9% GT3) were followed for 43.7 (32.9, 58.7) months. The incidence of OLDP was higher in patients with GT 3 (4.63/100PY) than non-GT 3 (0.60/100PY; P &amp;lt; 0.001). According to Cox multivariate analysis, GT 3 was significantly associated with OLDP (HR 6.41, 95% CI 1.82 - 22.56; P=0.004). The predictors of OLDP in patients with GT 3 were HCV recurrence (HR 12.15, 95% CI 3.18 - 46.46; P &amp;lt; 0.001) and FIB-4 &amp;gt; 3.25 (HR 16.40, 95% CI 1.03 - 39.81; P = 0.046) at baseline.ConclusionHCV GT 3-infected patients remain at a higher risk of OLDP even after achieving SVR by DAAs, especially patients with advanced liver fibrosis and at high risk for reinfection or virological late relapse.

Comparative effectiveness of antipsychotic treatment strategies for relapse prevention in first-episode schizophrenia in Finland: a population-based cohort study.

The best pharmacological treatment practices for relapse prevention in patients with first-episode schizophrenia are unclear. We aimed to assess different treatment strategies used before and after the first relapse, and their associations with subsequent relapse risk. In this population-based cohort study, we enrolled individuals (aged ≤45 years) with first-episode schizophrenia who were hospitalised and subsequently relapsed between 1996 and 2014 from the nationwide Finnish Hospital Discharge Register. Individuals who had not been taking antipsychotics within the year preceeding initial hospitalisation and who had a relapse within 5 years of discharge were included in the analyses. Treatment strategies were assessed during the 30 days before hospitalisation for the first relapse and 30 days after discharge and were categorised as either long-acting injectable, clozapine, non-clozapine oral antipsychotic monotherapy, non-clozapine oral antipsychotic polypharmacy, and antipsychotic non-use. Adjusted hazard ratios (aHRs) of the risk of second relapse based on treatment type were analysed with Cox regression models for 2 years after the first relapse, or until death or end of data linkage (Dec 31, 2017). People with lived experience of schizophrenia were not involved in the research and writing process. Between Jan 31, 1996 and Dec 31, 2017, 3000 individuals had their first psychosis relapse and were eligible for analysis. Mean age was 30·0 years (SD 7·6), 1069 (35·6%) of patients were women and 1931 (64·4%) men. No ethnicity data were available. 2148 (71·7%) had a second relapse within 2 years. Before first relapse, most individuals were either not using antipsychotics (n=1366 [45·5%]), or were using non-clozapine oral antipsychotic monotherapy (n=973 [32·4%]). Compared with continuing the same treatment strategy used before the first relapse, switching to clozapine was associated with the lowest risk of second relapse compared with continuing any non-clozapine oral antipsychotic monotherapy (aHR 0·66, 95% CI 0·49-0·89; relapse rate 73·2% with oral non-clozapine antipsychotic monotherapy continuation vs 57·1% with switch to clozapine). Switching to another non-clozapine oral antipsychotic monotherapy (0·99, 0·76-1·28) was approximately as unhelpful in preventing the next relapse as switching to antipsychotic non-use (1·07, 0·80-1·42). In patients with first-episode schizophrenia having their first psychosis relapse despite use of non-clozapine oral antipsychotics, continuation with the same antipsychotic modality or switch to another non-clozapine oral antipsychotic did not show evidence of being beneficial in relapse prevention, suggesting that clozapine should be started instead. This finding, together with existing knowledge of decreased risk of mortality associated with clozapine, challenges current treatment guidelines that recommend clozapine as a third-line treatment, resulting in treatment practices characterised by long delays to clozapine initiation. Sigrid Jusélius Foundation.

Development of a Novel Oral Therapeutic With a First-In-Class Mechanism Targeting Substance Addiction and Reduction in Risk of Relapse

Development of a Novel Oral Therapeutic With a First-In-Class Mechanism Targeting Substance Addiction and Reduction in Risk of Relapse

Use of pathological response versus RECIST assessment in predicting relapse-free survival following neoadjuvant immunotherapy for hepatocellular carcinoma.

633 Background: Immune checkpoint inhibitors (ICI) administered prior to liver resection (LR) lead to pathological responses in patients with hepatocellular carcinoma (HCC). However, the relative value of pathological versus radiological response in predicting relapse-free survival (RFS) remains unclear. Methods: We pooled patient-level data from 111 patients (pts) with HCC receiving ICI prior to LR as part of 5 phase I/II trials and observational clinical studies conducted in 12 centres in the United States, United Kingdom and Asia, as part of an academic consortium (NeoHCC). Pathological response was measured as the percentage of non-viable tumour in the resected specimen, with major (pMR) and complete pathological response (pCR) corresponding to ≥70% and 100% tumour regression. Radiological overall response rate (ORR) was assessed by RECIST v1.1 and modified RECIST (mRECIST) criteria. We correlated pathological response and ORR with RFS using Cox regression. Results: Pts received preoperative ICI between Oct 5, 2017, and Nov 15, 2023, mostly ICI combinations (69%, n=76). Most pts were male (78%, n=87) with viral chronic liver disease (66%, n=73), BCLC stage A HCC (55%, n=61). ORR was 28% per RECIST v1.1 and 32% per mRECIST criteria (available for n=81). Out of the 104 pathologically evaluable pts, pMR and pCR rates were 32% (n=33) and 18% (n=19). Radiological response by RECIST v1.1 showed a significant correlation with pathological response (R 2 = 0.43, p&lt;0.001). When using RECIST v1.1, 74% of pts with ORR achieved pMR vs 14% of those without ORR (n=23/31 vs 10/73, p&lt;0.001). However, 30% of pMR were not predicted by ORR (n=10/33). The discrepancy between pMR and ORR decreased using mRECIST. ORR per mRECIST was 83% in pMR pts (n=19/23), whereas it was 10% in non-pMR (n=5/51). After a median follow-up of 27.2 mos (95%CI 22.3-32.1), median RFS for the whole cohort was 43.6 mos (95%CI 28.3-NE). Achievement of pMR, pCR and ORR was associated with improved RFS (Table). However, reduction in the risk of relapse and/or death was higher in pts achieving pMR or pCR than ORR, regardless of the use of RECIST v1.1 or mRECIST. Conversely, pts without pMR had a lower mRFS than pts without ORR (28.3 mos [95%CI 12.8-43.8] and 32.8 mos [95%CI 13.7-51.9], respectively). Conclusions: Whilst radiological responses to neoadjuvant ICI are associated with improved RFS in pts with HCC, achievement of pMR is more accurate than RECIST and mRECIST-based responses in predicting for RFS, with lack of pMR identifying pts at a higher risk of relapse or mortality. Cox regression for RFS HR (95% CI) p value pCR 0.19 (0.05-0.78) 0.02 pMR 0.25 (0.10-0.66) 0.005 RECIST 1.1 0.34 (0.13-0.86) 0.02 mRECIST 0.38 (0.13-1.11) 0.08 RFS, relapse-free survival; HR, hazard ratio; CI, confidence interval; pCR, complete pathological response; pMR, major pathological response; mRECIST, modified RECIST.

A Comparison of Australian Oncology Clinicians' Smoking Cessation Care Practices for People Who Currently Smoke Versus Those Who Report Recently Stopping Smoking.

Smoking is a chronic relapsing condition that is under-reported in oncology settings. People who report current smoking (CS) and those who report recently quitting smoking (RQ) should receive cessation support when they are diagnosed with cancer. The study aimed to identify whether differences exist in the smoking cessation support given to CS and RQ in oncology and what advice is given regarding the benefits of cessation. A survey exploring smoking cessation practices was completed by oncology clinicians (medical, nursing, and allied health) at nine cancer centers in Australia. Data were analyzed using mixed-effects ordinal regression modeling. Across the 177 clinicians completing the survey, the reported provision of smoking cessation care was significantly higher for CS than for RQ in relation to asking about smoking status (odds ratio [OR] 3.03, p = 0.001), advice on the benefits of quitting (OR 2.86, p = 0.001), and advice to call the Quitline (OR 5.08, p < 0.001). Exploratory analyses indicated doctors and nurse specialists were four times more likely to report referring CS to a Quitline compared to RQ (OR 4.38, p = 0.001; OR 4.29, 95%, p = 0.005, respectively). The cessation benefits that clinicians most often cited to their patients was that quitting "can reduce the chance of developing treatment complications and side effects". The relative lack of smoking cessation care provided to RQ in oncology suggests that the high risk of smoking relapse is not well-recognized. Greater awareness and training are needed regarding advising RQ about the survival-specific benefits of continuing to not smoke, offering referrals, and offering follow-up support.

Multifaceted functions of the Wilms tumor 1 protein: From its expression in various malignancies to targeted therapy.

Wilms tumor 1 (WT1) is a multifaceted protein with dual functions, acting both as a tumor suppressor and as a transcriptional activator of oncogenes. WT1 is highly expressed in various types of solid tumors and leukemia, and its elevated expression is associated with a poor prognosis for patients. High WT1 expression also indicates a greater risk of refractory disease or relapse. Consequently, targeting WT1 is an effective strategy for disease prevention and relapse mitigation. Substantial information is available on the pathogenesis of WT1 in various diseases, and several WT1-targeted therapies, including chemical drugs, natural products, and targeted vaccines, are available. We provide a comprehensive review of the mechanisms by which WT1 influences malignancies and summarize the resulting therapeutic approaches thoroughly. This article provides information on the roles of WT1 in the pathogenesis of different cancers and provides insights into drugs and immunotherapies targeting WT1. The goal of this work is to provide a systematic understanding of the current research landscape and of future directions for WT1-related studies.

Region-specific neuroadaptations of CRF1 and CRF2 expression following heroin exposure in female rats

While stress increases vulnerability to development of addiction, the recruitment of corticotropin releasing factor (CRF) with excessive drug use heightens the risk of stress-induced relapse. CRF signaling is transmitted via CRF1 and CRF2 receptors, but the roles of these receptors in heroin self-administration and related neuroadaptations of the CRF system within mesolimbic brain loci are not well understood. In this study, we first investigated the causal role of CRF1 and CRF2 receptors in heroin self-administration. Intracerebroventricular (ICV) microinjections of antalarmin (a CRF1 antagonist) or astressin-2B (a CRF2 antagonist) caused brief, dose-dependent reductions in heroin self-administration in female rats, suggesting that these receptors play a critical role in heroin-motivated behaviors. We then used western blotting to examine neuroadaptive changes to CRF1 and CRF2 receptor expression in key forebrain and midbrain regions associated with opioid addiction. Female Long Evans rats treated with escalating doses of heroin for 16 days demonstrated significantly higher naloxone-precipitated withdrawal symptoms than saline-treated rats. Heroin-treated rats showed a significant decrease in CRF1 receptor protein expression in the ventral tegmental area (VTA) and an increase in the nucleus accumbens (NAc) but no changes in the prefrontal cortex (PFC), insula, dorsal striatum (dSTR), dorsal hippocampus (dHippo), anterior hypothalamus (HYPTH), amygdala, or substantia nigra (SN) as compared to saline-treated rats. After chronic heroin exposure, CRF2 receptor expression was significantly downregulated in the dHippo, VTA and HYPTH but not in the other brain regions we investigated. The results of this study suggest that: (1) CRF1 and CRF2 receptors play an important role in self-administration and (2) heroin exposure may lead to region-specific neuroadaptation of CRF1 and CRF2 receptors. Such neuroadaptations might in part contribute to the continuation of drug use and stress-induced relapse.

What is the relationship between exposure to environmental pollutants and severe mental disorders? A systematic review on shared biological pathways.

Severe mental disorders are multi-dimensional constructs, resulting from the interaction of genetic, biological, psychosocial, and environmental factors. Among the latter, pollution and climate change are frequently being considered in the etiopathogenesis of severe mental disorders. This systematic review aims to investigate the biological mechanisms behind the relationship between environmental pollutants, climate change, and mental disorders. An extensive literature search was performed on PubMed, Scopus, and APA PsycInfo databases according to the PRISMA guidelines. Articles were considered eligible if they involved humans or animals examining the association between exposure to environmental pollutants and if the resulting biological mechanisms that may have an impact on mental health and may support or even cause severe mental disorders (SMD) are assessed. For this reason, only studies dealing with biomarkers or biological pathways were taken into account. The 47 papers included in the review were divided into two groups: those conducted on human participants (15 studies) and those utilizing animal models (31 studies); one study included both humans and animals. Studies carried out with humans, which are mainly focused on measuring the impact of particulate matter (PM2.5 and PM10) exposure on mental health, showed an increased risk of depression or psychotic relapses through the inflammation and oxidative stress pathways, or through the alteration of the hypothalamic-pituitary-adrenal (HPA) axis. Animal models showed the potential impact of pollution on brain functioning through increased inflammatory responses, oxidative stress, HPA axis disruption, hippocampal damage, and neurotransmitters dysregulation. Our findings show that environmental pollutants have an impact on human mental health through different biological pathways. The biological mechanisms by which environmental pollution and climate change influence the onset and exacerbation of severe mental disorders are complex and include gene expression, inflammation, oxidative stress, and anatomical brain changes. A better understanding of those pathways is important for the progress of knowledge on the pathophysiology of severe mental disorders according to the one health model, that promotes a collaborative, multisectoral, and transdisciplinary approach across various levels to optimize health outcomes by recognizing the interconnectedness of humans, animals, plants, and their shared environment.

A first-in-human phase I trial with antibody drug conjugate ADCT-701 in neuroendocrine tumors and carcinomas.

TPS672 Background: Neuroendocrine neoplasms (NENs) consist of neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs), which are rare malignancies found in various anatomical sites, including the gastrointestinal tract, pancreatic islets, lungs, and adrenal glands. Poorly differentiated NECs are classified as high-grade carcinomas that bear resemblance to small-cell lung cancer (SCLC). Treatment for poorly differentiated NECs typically follows small-cell carcinoma guidelines, utilizing platinum-based regimens; however, these patients experience a high risk of relapse and demonstrate a limited response to additional systemic therapies. Adrenocortical carcinoma (ACC) is another rare malignancy associated with a median survival of approximately 14.5 months post-diagnosis, and advanced disease management options show limited efficacy. Currently, no targeted therapies have demonstrated significant effectiveness for this condition. Preclinical investigations have indicated that Delta-like non-canonical notch ligand 1 (DLK1) is expressed in various neuroendocrine neoplasms, including ACC, SCLC, neuroblastoma, pheochromocytoma, and paraganglioma. ADCT-701, a humanized antibody targeting DLK1, has shown potential in suppressing tumor growth and enhancing survival across multiple cancer models expressing this marker. Methods: This Phase I dose escalation study (NCT06041516) aims to enroll adult patients with histologically or cytologically confirmed neuroendocrine neoplasms or malignant ACC with evaluable disease, as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Participants will be part of a dose-finding trial. A 3+3 design is utilized to assess up to ten different dose levels of ADCT-701. Dose escalation continues unless dose-limiting toxicities occur, the maximum tolerated dose (MTD) is reached, or an optimal dose is established. The primary endpoint of the study is to ascertain the recommended phase 2 dose of ADCT-701 in patients with neuroendocrine neoplasms or malignant adrenocortical carcinoma. Secondary endpoints will assess safety, preliminary tumor activity, response rate, overall survival, pharmacokinetics, and the immunogenicity profile of ADCT-701. The trial aims to enroll up to 70 evaluable patients across a maximum of 10 dose levels. For further details, please refer to clinical trial information NCT06041516. Clinical trial information: NCT06041516 .

De-Escalation of Disease-Modifying Therapy in Multiple Sclerosis-A Danish Nationwide Cohort Study.

High-efficacy (HE) disease-modifying therapies (DMT) are increasingly used to treat multiple sclerosis (MS). Concerns arise when considering the decreasing efficacy and increasing risk of adverse events in aging patients. We aimed to describe disease activity and treatment trajectories in patients with MS who de-escalated from an HE DMT to an moderate-efficacy (ME) DMT. We performed a cohort study based on data from the Danish Multiple Sclerosis Registry (DMSR) including patients with relapsing-remitting MS (RRMS), who switched from an HE DMT to an ME DMT as defined by Danish authorities. We included patients from October 2007 to July 2023. Median follow-up time was 0.8 years (IQR 0.3-2.5). In total 333 patients (76.0% females, mean age: 45.1 years) de-escalated for various reasons. Most patients de-escalated from natalizumab or fingolimod (43.8% and 42.0%, respectively) to dimethyl fumarate (47.5%). At 2 years after de-escalation, the cumulative risk of relapse was 38% (95% CI 31-44) and 53% (95% CI 46-60) for inflammatory disease activity (relapses and/or radiological disease activity). Age (HR 0.96, 95% CI 0.94-0.98) and inflammatory disease activity prior to de-escalation (HR 2.05, 95% CI 1.45-2.91) were associated with inflammatory disease activity post de-escalation. De-escalation from primarily natalizumab and fingolimod did not effectively ensure disease stability in this cohort. Younger age and inflammatory disease activity prior to de-escalation were risk factors for inflammatory disease activity post de-escalation, which can help guide future studies on de-escalation.

Association of pre-surgical circulating tumor DNA detection, use of sublobar resection with risk of recurrence in stage I non-small cell lung cancer.

Sublobar resection is increasingly recognized as an effective treatment for early-stage NSCLC. However, no studies to date have investigated the potential role of preoperative ctDNA detection in guiding surgical decisions, such as opting for sublobar resection, in stage I NSCLC. Patients with solid-dominant (CTR>0.5), clinical stage I NSCLC were prospectively recruited between March 2014 and December 2020. Pre-surgical plasma samples were analyzed using a tumor-naïve, methylation-based cell-free DNA assay. The impact of sublobar resection versus lobectomy on recurrence-free survival (RFS) was assessed according to pre-surgical ctDNA status. Associations between pre-surgical ctDNA detection and clinicopathologic factors were also investigated. The analysis included 544 patients (178 women [33 %]; median age 66 [IQR, 60-71] years). Pre-surgical ctDNA was detected in 188 (35 %) patients. In patients without presurgical ctDNA, sublobar resection did not significantly increase the risk of relapse (adjusted HR, 1.01, p = 0.98). However, among ctDNA-positive patients, sublobar resection was associated with an increased risk of relapse (adjusted HR, 2.25; 95 % CI, 1.12-4.54; p = 0.024). Patients with presurgical ctDNA had higher rates of nodal upstaging (OR, 3.58; p < 0.001) and exhibited higher pathologic grade (p = 0.021), perineural invasion (p < 0.001), and lymphovascular invasion (p < 0.001). Pre-surgical tumor-naïve ctDNA analysis holds promise in identifying patients with aggressive tumors that may not be sufficiently managed with sublobar resection. This approach can help personalize treatment strategies, potentially improving outcomes for patients with early-stage NSCLC.

Prevalence, clinicopathologic features and long-term overall survival of early breast cancer patients eligible for adjuvant abemaciclib and/or ribociclib.

Adjuvant CDK4/6 inhibitors (abemaciclib and ribociclib) associated with endocrine therapy reduced the risk of relapse for HR+/HER2- early breast cancer (eBC) patients in the monarchE and NATALEE trials. In this population-based study, we assess the real-life proportion, and long-term prognosis of patients treated for HR+/HER2- eBC between 2005 and 2015, and eligible for adjuvant CDK4/6 inhibitors according to these trial inclusion criteria. Among 3,103 patients, N = 440 (14.2%) would have been eligible for adjuvant abemaciclib, and N = 1068 (34.4%) for ribociclib. Node-negative patients who would have been eligible for adjuvant ribociclib represent 10.9% of the eligible population. 21.7% of patients now eligible for adjuvant abemaciclib, and 32.1% for ribociclib did not receive (neo)adjuvant chemotherapy. After a median follow-up of 144.7 months, 10-year overall survival confirms the prognostic relevance of the inclusion criteria used in pivotal trials. This study provides real-life insights into the prevalence, clinicopathological characteristics and long-term prognosis of HR+/HER2- eBC patients now eligible for adjuvant CDK4/6 inhibitors.

The Role of Candidate Polymorphisms in Drug Transporter Genes on High-Dose Methotrexate in the Consolidation Phase of the AIEOP-BFM ALL 2009 Protocol.

High-dose methotrexate (HD-MTX) infusions are commonly used to consolidate remission in children with acute lymphoblastic leukemia (ALL). We investigate the potential role of candidate polymorphisms in SLCO1B1 (rs4149056 and rs2306283), ABCB1 (rs1045642), ABCC2 (rs717620), ABCC3 (rs9895420), and ABCC4 (rs7317112) drug transporters genes on HD-MTX pharmacokinetics and patients' outcome (meant both as relapse and drug-related toxicities) in an Italian cohort of 204 ALL pediatric patients treated according to the AIEOP-BFM ALL 2009 protocol. TaqMan SNP genotyping assays determined patient's genotypes. Measurements of HD-MTX plasma concentration were available for 814 HD-MTX courses in 204 patients; MTX clearance was estimated by a two-compartmental linear pharmacokinetic model with first-order elimination and a Bayesian approach, via ADAPT. Independent contributions of age and ABCC4 SNP rs7317112 (A>G, intronic) on MTX clearance were detected in a multivariate analysis (p = 1.57 × 10-8 and p = 2.06 × 10-5, respectively), suggesting a delayed elimination of the drug in older patients and an accelerated one in carriers of the variant GG genotype. After multiple corrections, the association between ABCC2 SNP rs717620 (-24 C>T) and severe hematological toxicity was found (p < 0.005). Moreover, SLCO1B1 SNP rs4149056 (c.521T>C, p.V174A) affected patients' outcomes: carriers of the variant C allele presented a reduced risk of relapse compared to wild-type TT (hazard risk: 0.27, 95% confidence interval [CI]: 0.08-0.90, p = 0.037). Taken together, these data highlighted the importance of variants in drug transporters genes on HD-MTX disposition in the AIEOP-BFM ALL 2009 protocol consolidation phase, and their putative role as predictive markers of outcome.

Hypoalbuminemia and Nutritional Status in Children With Cancer.

In children with cancer, poor nutritional status adversely affects outcomes. Hypoalbuminemia is common in pediatric oncology patients, and in some groups is associated with inferior survival rates. We sought to determine if serum albumin associates with body mass index (BMI) percentile and if combining serum albumin and BMI is associated with survival. We performed a single institution, retrospective review of pediatric oncology patients and collected data regarding baseline BMI, serum albumin, and survival outcome. Combining baseline BMI and serum albumin, we classified patients' nutritional status as adequately nourished, mildly/moderately depleted, and severely depleted. In a cohort of 490 pediatric oncology patients, hypoalbuminemia prevalence was 49%. Serum albumin did not associate with BMI percentile for age. Overall, those defined as severely depleted had an increased risk of relapse or death at 3 and 6 months from chemotherapy initiation compared with those defined as adequately nourished (hazard ratio [HR]=2.37, 95% CI 1.29-4.37 at 3 months, p=0.006; HR=1.77, CI 1.11-2.82 at 6 months, p=0.017). Statistical analyses suggest the inferior survival in those deemed severely depleted was primarily driven by hypoalbuminemia rather than BMI. In this cohort of pediatric oncology patients, serum albumin did not correlate with BMI. Severe hypoalbuminemia is an adverse prognostic factor. Baseline BMI had a minimal impact on relapse-free survival and overall survival, independently or in combination with hypoalbuminemia.

Use of 18F-fluorodeoxyglucose Positron Emission Tomography to Monitor Disease Activity in Patients With Giant Cell Arteritis on Tocilizumab.

The objective of this study was to assess the value of 18F-fluorodeoxyglucose (FDG)- positron emission tomography (PET) scans to monitor disease activity in patients with giant cell arteritis (GCA) on tocilizumab. Patients with GCA were recruited into a prospective cohort in which they underwent clinical, laboratory, and imaging assessments, including FDG-PET. FDG-PET scans were interpreted as active or inactive based on global impression by two independent readers. The PET Vascular Activity Score (PETVAS) was calculated to quantify arterial FDG uptake (scale 0-27). Vascular FDG-PET findings were described in patients with GCA on tocilizumab for at least six months. For patients in established clinical remission, FDG-PET findings were compared between those treated with tocilizumab versus glucocorticoid monotherapy. A total of 36 patients with GCA underwent FDG-PET imaging on tocilizumab. Five patients had active clinical symptoms, and FDG-PET scans were active in all cases (PETVAS range: 20-27). For the 31 patients in clinical remission on tocilizumab, FDG-PET was active in 16 of these patients (52%) across a wide range of PETVAS (range 11-27). There were no associations between FDG-PET activity during remission and historical clinical features or longitudinal outcomes, including relapse risk or angiographic progression of disease. PETVAS was significantly lower during clinical remission in patients treated with tocilizumab compared to an additional 12 patients treated with glucocorticoid monotherapy (PETVAS 18 vs 24; P = 0.02). FDG-PET has limited value to guide management decisions or inform prognosis when obtained during remission in patients with GCA on tocilizumab. Compared to glucocorticoid monotherapy, tocilizumab significantly reduces, but often does not eliminate, vascular inflammation in GCA.

Treatment of high-risk myelodysplastic syndromes.

Myelodysplastic syndrome (MDS) is considered to be a heterogeneous myeloid malignancy with a common origin in the hematopoietic stem cell compartment and is generally divided into lower- and higher-risk forms. While the treatment goals for lower-risk MDS are to decrease transfusion requirements and transformation into acute leukemia, the major aims for higher-risk MDS are to prolong survival and ultimately cure the patient. Although novel agents such as luspatercept and imetelstat have recently been approved as new treatment options for lower-risk MDS, hypomethylating agents currently remain the only approved non-transplant option for higher-risk MDS and are the standard of care for patients not eligible for allogeneic hematopoietic stem cell transplantation (HSCT). Combinations with other drugs as first-line treatment have to date not proven more efficacious than monotherapy in higher-risk MDS, and outcome after the failure of treatment with hypomethylating agents is poor. The only potential cure and standard of care for eligible patients is HSCT and even though the number of transplanted - especially older - MDS patients has increased over time due to better management and greater donor availability, the majority of MDS patients will not be eligible for this curative approach. Current challenges include decreasing the relapse risk, the main cause of HSCT failure. This review summarizes current knowledge on the options of transplant and non-transplant treatment approaches for these patients and demonstrate the unmet clinical need for more effective therapies.

Relapse detection in the Danish surveillance program of patients with clinical stage I seminoma: a nationwide study.

Active surveillance is a recommended management strategy for patients with clinical stage I (CSI) seminoma. This study aims to identify patterns of relapse detection methods in an unselected population-based cohort of CSI patients and provide evidence for a risk-adapted follow-up program. A total of 924 patients with CSI seminoma were identified in the prospective Danish Testicular Cancer database. Retrospectively collected clinical data were used for descriptive analyses of patterns in detection methods. Additionally, we explored a risk-adapted surveillance approach based on recently identified risk factors for relapse, classifying patients into low- and non-low-risk groups. At 60 months, the 5-year cumulative relapse risk was 16%, with 146 relapses during surveillance. Relapses were detected by imaging alone in 71% of cases, imaging combined with elevated serum tumor markers (STMs) in 18%, isolated elevation of STMs in 8%, and by self-referral due to symptoms in 3%. No relapses were detected by abnormal findings at a physical examination. In total, 134 (92%) relapses were localized to retroperitoneal lymph nodes, primarily without additional spread. The 5-year relapse risk in patients with low risk of relapse was 9% compared to 28% in patients in the non-low-risk group. This study highlights that the surveillance program can detect relapses at an early stage. Reduction of visits and omission of routine physical examinations can safely be considered for patients with a low risk of relapse, while further research is needed to optimize follow-up and treatment for patients at higher risk of relapse.