Do we need reshape rTNM staging system for ipsilateral breast tumor recurrence of breast cancer? A population-based, propensity score matched cohort study.

BACKGROUND: The aim of the study was to explore the role of recurrent TNM (rTNM) staging in predicting prognosis for ipsilateral breast tumor recurrence (IBTR) and determine the optimal treatment strategy for IBTR. METHOD: IBTR cases were identified from the Surveillance, Epidemiology, and End Results (SEER) database spanning the years 2000-2018. Cox proportional hazards analysis was performed to examine factors associated with overall survival (OS) and breast cancer-specific survival (BCSS). Propensity score matching (PSM) was employed to match IBTR with primary early breast cancer (EBC) based on clinicopathological characteristics. Investigations into the impact of different therapies were also included. RESULTS: Of the 4375 IBTR cases included in the study, the 5-year OS was 87.1%, 71.6% and 58.7% in rTNM stages I, II and III, respectively. After PSM, while IBTR patients had worse survival to primary EBC patients, prognosis of IBTR for different rTNM stage always closely aligned with the corresponding stage of primary EBC. Repeat breast-conserving surgery (BCS) with radiation therapy was equivalent to mastectomy with respect to OS and BCSS. Chemotherapy was favorable for OS and BCSS in estrogen receptor (ER)-negative IBTR or IBTR occurring within a 60-month interval. CONCLUSIONS: rTNM staging system has an outstanding prognostic value for survival outcome of patients with IBTR, and IBTR and primary EBC may have potentially analogous features in the context of TNM staging. BCS plus radiation therapy may be an alternative. IBTR cases who have experienced recurrence with short intervals and with ER-negative tumors might benefit from chemotherapy.

Should Palpable Nodes Be Exclusionary in Patients Who Are Otherwise Candidates for ACOSOG Z0011-Type Trials?

BACKGROUND: Palpable nodes were exclusionary in American College of Surgeons Oncology Group (ACOSOG) Z0011, while SINODAR-ONE excluded those with positive axillary nodes by palpation and ultrasound. To determine whether clinical nodal status should be exclusionary in those fulfilling pathologic criteria for ACOSOG Z0011 and similar trials, this study analyzed the accuracy and implications of clinical nodal positivity. METHODS: Patients ≥ 18 years old with cT1-T2, cN0-cN1, M0 breast cancer were identified in the National Cancer Database between 2004 and 2019. Subset characteristics of cN1 and cN0 were compared with respect to final pathologic nodal status and overall survival (OS). RESULTS: Of 57,823 patients identified, 77.0% were cT1 and 23.0% were cT2. Of the 93.9% of patients who were staged as cN0, 16.7% were pN1; of the remaining 6.1% staged as cN1, 9.6% were found to be pN0. Among cN1/pN0 patients, 14.9% underwent axillary dissection without sentinel node biopsy. There was no difference in adjusted OS for patients staged as cN0 versus cN1 who were found to be pN1 (HR 1.13, 95% CI 0.93-1.37, p = 0.22), a finding that persisted on subset analysis in those with two positive nodes (HR 0.91, 95% CI 0.62-1.33, p = 0.63). CONCLUSIONS: Clinical nodal stage does not affect OS in pN1 patients. Clinical nodal assessment can both overstage patients and result in unnecessary axillary surgery. These data suggest that cN1 patients who are otherwise candidates for a Z0011-like paradigm should still be considered eligible. Their final candidacy should be determined by surgical lymph node pathology and not preoperative clinical status.

Clinical Staging for Personality Disorders in Older Adults.

OBJECTIVE: This scientific research aimed to investigate the feasibility of implementing a clinical staging (CS) model for personality disorders (PDs) in older adults. The CS model could provide valuable insights into the life course of personality pathology, prognosis, and treatment decisions for PDs in older adults. METHODS/DESIGN: The study employed an international Delphi methodology with three rounds and involved 21 experts. RESULTS: Consensus was achieved on 12 out of 17 statements, confirming the viability of a CS model for PDs in older adults. The proposed model incorporates the Alternative Model for PDs, criterion A, and integrates life course information, distinguishing between chronic PD, re-emergent PD, late-onset PD, and past PD. CONCLUSION: The findings suggest that international experts support the implementation of a CS model for PDs in older adults, considering both the severity of personality functioning and the retrospective life course of PD expression.

Characterising illness stages and recovery trajectories of eating disorders in young people via remote measurement technology (STORY): a multi-centre prospective cohort study protocol.

BACKGROUND: Eating disorders (EDs) are serious, often chronic, conditions associated with pronounced morbidity, mortality, and dysfunction increasingly affecting young people worldwide. Illness progression, stages and recovery trajectories of EDs are still poorly characterised. The STORY study dynamically and longitudinally assesses young people with different EDs (restricting; bingeing/bulimic presentations) and illness durations (earlier; later stages) compared to healthy controls. Remote measurement technology (RMT) with active and passive sensing is used to advance understanding of the heterogeneity of earlier and more progressed clinical presentations and predictors of recovery or relapse. METHODS: STORY follows 720 young people aged 16-25 with EDs and 120 healthy controls for 12 months. Online self-report questionnaires regularly assess ED symptoms, psychiatric comorbidities, quality of life, and socioeconomic environment. Additional ongoing monitoring using multi-parametric RMT via smartphones and wearable smart rings ('Oura ring') unobtrusively measures individuals' daily behaviour and physiology (e.g., Bluetooth connections, sleep, autonomic arousal). A subgroup of participants completes additional in-person cognitive and neuroimaging assessments at study-baseline and after 12 months. DISCUSSION: By leveraging these large-scale longitudinal data from participants across ED diagnoses and illness durations, the STORY study seeks to elucidate potential biopsychosocial predictors of outcome, their interplay with developmental and socioemotional changes, and barriers and facilitators of recovery. STORY holds the promise of providing actionable findings that can be translated into clinical practice by informing the development of both early intervention and personalised treatment that is tailored to illness stage and individual circumstances, ultimately disrupting the long-term burden of EDs on individuals and their families.

Factors Associated with Transition to Serious Mental Illness.

OBJECTIVE: There is increasing interest in early intervention and detection strategies for youth at-risk of developing a serious mental illness (SMI). Little is known about early factors that may be related to the later development of a SMI; thus, the aim of this study was to determine what clinical factors might relate to the development of in this study psychosis, bipolar disorder and severe or recurrent major depression in at-risk youth. METHOD: The sample consisted of 162 youth aged 12-26 years at different stages of risk. Thirty-one participants developed a SMI during the study. Those who made a transition were compared on a range of baseline clinical and functional measures with those who did not make the transition. A Cox regression model was used to assess the association between measures and later development of a SMI. RESULTS: Female sex, attenuated psychotic symptoms as assessed with the Scale of Psychosis-Risk Symptoms (SOPS) and ratings on the K-10 Distress Scale, were found to be significantly associated with the later transition to mental illness. Females were 2.77 times more likely to transition compared to males. For the SOPS and K-10 scales, there is a 14% increase in the transition rate relative to a one-scale increase in SOPS and a 7% increase in the transition rate relative to a one-point increase in the K-10. CONCLUSIONS: Results from these longitudinal data provide further insight into the specific clinical measures that may be pertinent in early detection of mental illnesses.

Diagnostic Potential of miR-143-5p, miR-143-3p, miR-551b-5p, and miR-574-3p in Chemoresistance of Locally Advanced Gastric Cancer: A Preliminary Study.

Gastric cancer (GC) is one of the most frequently diagnosed cancers in the world. Although the incidence is decreasing in developed countries, the treatment results are still unsatisfactory. The standard treatment for locally advanced gastric cancer (LAGC) is gastrectomy with perioperative chemotherapy. The association of selected microRNAs (miRNAs) with chemoresistance was assessed using archival material of patients with LAGC. Histological material was obtained from each patient via a biopsy performed during gastroscopy and then after surgery, which was preceded by four cycles of neoadjuvant chemotherapy (NAC) according to the FLOT or FLO regimen. The expression of selected miRNAs in the tissue material was assessed, including miRNA-21-3p, miRNA-21-5p, miRNA-106a-5p, miRNA-122-3p, miRNA-122-5p, miRNA-143-3p, miRNA-143-5p, miRNA-203a-3p, miRNA-203-5p, miRNA-551b-3p, miRNA-551b-5p, and miRNA-574-3p. miRNA expression was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The response to NAC was assessed using computed tomography of the abdomen and chest and histopathology after gastrectomy. The statistical analyses were performed using GraphPad Prism 9. The significance limit was set at p < 0.05. We showed that the expression of miR-143-3p, miR-143-5p, and miR-574-3p before surgery, and miR-143-5p and miR-574-3p after surgery, decreased in patients with GC. The expression of miR-143-3p, miR-143-5p, miR-203a-3p, and miR-551b-5p decreased in several patients who responded to NAC. The miRNA most commonly expressed in these cases was miRNA-551b-5p. Moreover, it showed expression in a patient whose response to chemotherapy was inconsistent between the histopathological results and computed tomography. The expression of miR-143-3p, miR-143-5p, miR-203a-3p, and miR-551b-5p in formalin-fixed paraffin-embedded tissue (FFPET) samples can help differentiate between the responders and non-responders to NAC in LAGC. miR-143-3p, miR-143-5p, and miR-574-3p expression may be used as a potential diagnostic tool in GC patients. The presence of miR-551b-5p may support the correct assessment of a response to NAC in GC via CT.

The dynamic relationship between sleep and psychotic experiences across the early stages of the psychosis continuum.

BACKGROUND: Psychotic disorders develop gradually along a continuum of severity. Understanding factors associated with psychosis development, such as sleep, could aid in identification of individuals at elevated risk. This study aimed to assess (1) the dynamic relationship between psychotic experiences (PEs) and sleep quality and quantity, and (2) whether this relationship differed between different clinical stages along the psychosis continuum. METHODS: We used daily diary data (90 days) of individuals (N = 96) at early stages (i.e. before a first diagnosis of psychosis) along the psychosis continuum. Multilevel models were constructed with sleep quality and sleep quantity as predictors of PEs and vice versa. Post-hoc, we constructed a multilevel model with both sleep quality and quantity as predictors of PEs. In addition, we tested whether associations differed between clinical stages. RESULTS: Within persons, poorer sleep predicted next day PEs (B = -0.02, p = 0.01), but not vice versa. Between persons, shorter sleep over the 90-day period predicted more PEs (B = -0.04, p = 0.002). Experiencing more PEs over 90-days predicted poorer (B = -0.02, p = 0.02) and shorter (B = -1.06, p = 0.008) sleep. We did not find any significant moderation effects for clinical stage. CONCLUSIONS: We found a bidirectional relationship between sleep and PEs with daily fluctuations in sleep predicting next day PEs and general patterns of more PEs predicting poorer and shorter sleep. Our results highlight the importance of assessing sleep as a risk marker in the early clinical stages for psychosis.

The inaccuracies of gastric adenocarcinoma clinical staging and its predictive factors.

INTRODUCTION: Accurate clinical staging (CS) of gastric adenocarcinoma is important to guide treatment planning. Our objectives were to (1) assess clinical to pathologic stage migration patterns for patients with gastric adenocarcinoma, (2) identify factors associated with inaccurate CS, and (3) evaluate the association of understaging with survival. METHODS: The National Cancer Database was queried for patients who underwent upfront resection for stage I-III gastric adenocarcinoma. Multivariable logistic regression was used to detect factors associated with inaccurate understaging. Kaplan-Meier analyses and cox proportional hazards regression were performed to assess overall survival (OS) for patients with inaccurate CS. RESULTS: Of 14 425 analyzed patients, 5781 (40.1%) patients were inaccurately staged. Factors associated with understaging included treatment at a Comprehensive Community Cancer Program, presence of lymphovascular invasion, moderate to poor differentiation, large tumor size, and T2 disease. Based on overall CS, median OS was 51.0 months for accurately staged patients and 29.5 months for understaged patients (<0.001). CONCLUSION: Clinical T-category, large tumor size, and worse histologic features lead to inaccurate CS for gastric adenocarcinoma, impacting OS. Improvements to staging parameters and diagnostic modalities focusing on these factors may improve prognostication.

Radiologic Extranodal Extension of Metastatic Lymph Nodes in Patients With Non-Small Cell Lung Cancer: Prognostic Utility and Diagnostic Performance.

BACKGROUND. Pathologic extranodal extension (ENE) in metastatic lymph nodes (LNs) has been associated with unfavorable prognosis in patients with non-small cell lung cancer (NSCLC). OBJECTIVE. The purpose of this article was to evaluate the prognostic utility of radiologic ENE and its diagnostic performance in predicting pathologic ENE in patients with NSCLC. METHODS. This retrospective study included 382 patients (mean age, 67 ± 10 [SD] years; 297 men, 85 women) diagnosed with NSCLC and clinical N1 or N2 disease between January 2010 and December 2016. Two thoracic radiologists reviewed staging chest CT examinations to record subjective overall impression for radiologic ENE (no ENE, possible/probable ENE, or unambiguous ENE), reviewing 30 examinations in consensus and the remaining examinations independently. Kaplan-Meier survival analysis and multivariable Cox proportional hazards model were used to evaluate the utility of radiologic ENE in predicting overall survival (OS). Prognostic utility of radiologic ENE was also assessed in patients with clinical N2a disease. In patients who underwent surgery, sensitivity and specificity were determined of radiologic unambiguous ENE in predicting pathologic ENE. RESULTS. The 5-year OS rates for no ENE, possible/probable ENE, and unambiguous ENE were 44.4%, 39.1%, and 20.9% for reader 1 and 45.7%, 36.6%, and 25.6% for reader 2, respectively. Unambiguous ENE was an independent prognostic factor for worse OS (reader 1: adjusted HR, 1.72, p = .008; reader 2: adjusted HR, 1.56, p = .03), whereas possible/probable ENE was not (reader 1: adjusted HR, 1.18, p = .33; reader 2: adjusted HR, 1.21, p = .25). In patients with clinical N2a disease, 5-year OS rate in patients with versus without unambiguous ENE for reader 1 was 22.2% versus 40.6% (p = .59) and for reader 2 was 27.6% versus 41.0% (p = .49). In 203 patients who underwent surgery (66 with pathologic ENE), sensitivity and specificity of radiologic unambiguous ENE for predicting pathologic ENE were 11% and 93% for reader 1 and 23% and 87% for reader 2. CONCLUSION. Radiologic unambiguous ENE was an independent predictor of worse OS in patients with NSCLC. The finding had low sensitivity but high specificity for pathologic ENE. CLINICAL IMPACT. Radiologic ENE may have a role in NSCLC staging workup and treatment selection.

The efficacy and safety of cariprazine in the early and late stage of schizophrenia: a post hoc analysis of three randomized, placebo-controlled trials.

BACKGROUND: The aim of the post hoc analysis was to better understand the efficacy and safety of cariprazine in patients with schizophrenia for less than 5 years (early stage) and for more than 15 years (late stage). METHODS: Data from three phase II/III randomized, double-blind, placebo-controlled trials with similar design in patients with acute exacerbation of schizophrenia were pooled and patients with early and late stage of schizophrenia were determined. A mixed-effects model for repeated measures approach was applied and least square (LS) mean changes from baseline to week 6 on the Positive and Negative Syndrome Scale (PANSS) total and factor scores were reported. Descriptive statistics were used for safety analyses including treatment emergent adverse events (TEAEs) and discontinuation rates. RESULTS: Overall, 460 patients were identified as being in the early and 414 in the late stage of schizophrenia. The pooled analysis evaluating mean change from baseline to week 6 in the PANSS total score indicated statistically significant difference between cariprazine and placebo in favor of cariprazine in both the early (LS mean difference [LSMD] -7.5 P < .001) and late stage (LSMD -6.7, P < .01) subpopulation. Early stage patients experienced similar amount of TEAEs (CAR 67.3%, PBO 54.1%) as patients in the late stage (CAR 69.6%, PBO 65.6%). CONCLUSION: In conclusion, cariprazine, a potent D3-D2 partial agonist has been found to be safe and effective in the treatment of early and late stage schizophrenia.

Impact of the preoperative clinical N stage on the prognosis of patients with colon cancer.

AIM: Although preoperative clinical staging (cStage) is performed for most cancer patients, limited information is currently available on the relationship with postoperative prognosis. We herein investigated the relationship between cStage and prognosis of colon cancer (CC) patients, particularly focusing on the presence or absence of clinical lymph node (LN) metastasis. METHOD: This was a retrospective study on 840 consecutive patients with colon adenocarcinoma who underwent radical resection at our institution between January 2007 and December 2018. A Kaplan-Meier curve was used to analyse the prognosis of two groups: cN(+)pN(-); a group preoperatively diagnosed with clinical LN metastasis positive, but with no pathological LN metastasis postoperatively, and cN(-)pN(-); a group without clinical and pathological LN metastasis. We also investigated whether a clinical diagnosis is a more accurate prognostic factor than other clinical factors. RESULTS: Among pN(-) cases, the 5-year recurrence-free survival rate was significantly lower in preoperatively diagnosed cN(+) cases than in cN(-) cases (79.4% vs. 95.6%, 3.04 years vs. 3.85 years, p < 0.01). In a multivariate analysis of various preoperative clinical factors in pStage II cases, including high risk factors for pStage II CC, cN(+) was identified as an independent prognostic factor (hazard ratio: 2.06, 95% CI: 1.02-4.27, p = 0.04). CONCLUSION: Preoperatively over-staged cN cases had a poorer prognosis than cases without over-staging, indicating its potential as a prognostic factor. In addition to already known high risk factors in pStage II cases, the preoperative cStage may be an indication for adjuvant chemotherapy.

Examining the psychobiological response to acute social stress across clinical stages and symptom trajectories in the early psychosis continuum.

The stress-vulnerability model has been repeatedly highlighted in relation to the risk, onset and course of psychosis, and has been independently studied in clinical high-risk (CHR) and first-episode psychosis (FEP) populations. Notable in this literature, however, is that there are few studies directly comparing markers of stress response across progressive stages of illness. Here we examined the psychobiological response to the Trier Social Stress Test in 28 CHR (mean age 19.1) and 61 FEP (age 23.0) patients, in order to understand the stage(s) or trajectories in which differences in subjective stress or physiological response occur. The overall clinical sample had greater perceived stress and blunted cortisol (FEP + CHR, n = 89, age 21.7) compared with healthy controls (n = 45, age 22.9). Additional analyses demonstrated elevated heart rate and systolic blood pressure in FEP compared with CHR, but there were no further differences in physiological parameters (cortisol, heart rate, or blood pressure) between stage- or trajectory-based groups. Together, this suggests that individual stress response markers may differentially emerge at particular stages en route to psychosis - and demonstrates how stage-based analyses can shed light on the emergence and evolution of neurobiological changes in mental illness.

The therapeutic utility of combining dynamic contrast-enhanced magnetic resonance imaging with arterial spin labeling in the staging of nasopharyngeal carcinoma.

BACKGROUND: To research the pathological and clinical staging uses of arterial spin labeling (ASL) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: 64 newly diagnosed nasopharyngeal carcinoma (NPC) patients were enrolled from December 2020 to January 2022, and 3.0 T MRI (Discovery 750W, GE Healthcare, USA) were used for ASL and DCE-MRI scans. The DCE-MRI and ASL raw data were processed post-acquisition on the GE image processing workstation (GE Healthcare, ADW 4.7, USA). The volume transfer constant (Ktrans), blood flow (BF), and accompanying pseudo-color images were generated automatically. Draw the region of interest (ROIs), and the Ktrans and BF values for each ROI were recorded separately. Based on pathological information and the most recent AJCC staging criteria, patients were divided into low T stage groups = T1-2 and high T stage groups = T3-4, low N stage groups = N0-1 and high N stage groups = N2-3, and low AJCC stage group = stage I-II and high AJCC stage group = stage III-IV. The association between the Ktranst and BF parameters and the T, N, and AJCC stages was compared using an independent sample t-test. Using a receiver operating characteristic (ROC) curve, the sensitivity, specificity, and AUC of Ktranst, BFt, and their combined use in T and AJCC staging of NPC were investigated and assessed. RESULT: The tumor-BF (BFt) (t = - 4.905, P < 0.001) and tumor-Ktrans (Ktranst) (t = - 3.113, P = 0.003) in the high T stage group were significantly higher than those in the low T stage group. The Ktranst in the high N stage group was significantly higher than that in the low N stage group (t = - 2.071, P = 0.042). The BFt (t = - 3.949, P < 0.001) and Ktranst (t = - 4.467, P < 0.001) in the high AJCC stage group were significantly higher than those in the low AJCC stage group. BFt was moderately positively correlated with the T stage (r = 0.529, P < 0.001) and AJCC stage (r = 0.445, P < 0.001). Ktranst was moderately positively correlated with T staging (r = 0.368), N staging (r = 0.254), and AJCC staging (r = 0.411). There was also a positive correlation between BF and Ktrans in gross tumor volume (GTV) (r = 0.540, P < 0.001), parotid (r = 0.323, P < 0.009) and lateral pterygoid muscle (r = 0.445, P < 0.001). The sensitivity of the combined application of Ktranst and BFt for AJCC staging increased from 76.5 and 78.4 to 86.3%, and the AUC value increased from 0.795 and 0.819 to 0.843, respectively. CONCLUSION: Combining Ktrans and BF measures may make it possible to identify the clinical stages in NPC patients.

Effectiveness of a transdiagnostic emotion regulation training in an at-risk sample: a randomized-controlled trial of group-based training versus self-help bibliotherapy.

OBJECTIVES: Subclinical psychotic, depression, and anxiety symptoms form a transdiagnostic 'at-risk state' for the development of mental disorders. Emotion regulation has been identified as a transdiagnostic factor relevant to the formation of these symptoms that can be successfully addressed in clinical interventions. Here, we tested whether a group-based emotion regulation training would be effective in reducing distress and at preventing the transition to mental disorders in an at-risk sample. METHODS: Participants with distressing subclinical psychotic, depression, or anxiety symptoms (n = 138) were randomly allocated to either the 8-week group-based affect regulation training (ART; Springer, New York) or an 8-week self-help bibliotherapy (BT). They underwent biweekly measurements during the intervention, as well as at a six- and 12-month follow-up. In an exploratory analysis, we tested whether the ART would be superior to BT in preventing the transition to any mental disorder at 12-month follow-up. We also tested for differences in trajectories of psychopathology and emotion regulation (via questionnaires) and emotion regulation in daily life (via the experience-sampling method). RESULTS: Participants in the ART condition showed a greater improvement of emotion regulation in daily life than those with BT, but the ART was not superior over BT in preventing the transition to mental disorders. There were significant longitudinal reductions from pre- to post-intervention for general psychopathology and symptoms but no superiority of the ART over BT. CONCLUSIONS: Despite its efficacy in improving emotion regulation skills, the ART does not produce effects on psychopathology that justify its recommendation over self-help approaches.

The full spectrum of clinical stages of psychosis among mentally ill prisoners in New South Wales (NSW), Australia.

Research on the association between psychosis and criminal offending has typically focused on violent offenders with chronic psychotic illness. This stages of psychosis in prison (SOPP) study used a clinical staging approach to identify adult men referred to prison mental health services who had an at-risk mental state (ARMS), first episode of psychosis (FEP) or an established psychotic illness. Of the 105 participants included, 6% were determined to have FEP, 6% met ARMS criteria and the remainder had an established psychotic illness. Compared to a prison control sample, individuals on the psychosis spectrum were found to have higher levels of social disadvantage and other co-occurring mental health and substance use problems but were not more likely to have committed a violent offence. These findings support the notion that risk of criminal justice contact and complex illness burden exist across the full spectrum of psychotic illness.

Higher accuracy of [68 Ga]Ga-DOTA-FAPI-04 PET/CT comparing with 2-[18F]FDG PET/CT in clinical staging of NSCLC.

PURPOSE: This study aimed to explore the clinical staging performance of [68 Ga]Ga-DOTA-FAPI-04 PET/CT compared with that of 2-[18F]FDG PET/CT in non-small cell lung cancer (NSCLC) patients lesion by lesion. METHODS: A total of 134 diagnosed or suspected NSCLC patients were enrolled in the prospective study (ChiCTR2000038080); they received paired 2-[18F]FDG PET/CT and [68 Ga]Ga-DOTA-FAPI-04 PET/CT. Of these patients, the retrospective analysis of 74 NSCLC patients with pathological results was conducted from primary tumor (T) diagnosis, lymph node (N), and metastatic lesion (M) staging. The imaging characteristics of the lung nodules and suspected metastases were obtained and analyzed, and the staging performance of 2-[18F]FDG PET/CT and [68 Ga]Ga-DOTA-FAPI-04 PET/CT was compared. RESULTS: For T diagnosis, [68 Ga]Ga-DOTA-FAPI-04 showed better diagnostic performance than 2-[18F]FDG in 79 lung nodules of 72 patients, especially for nonsolid and small-dimension adenocarcinoma nodules. For N staging, 98 lymph nodes (LNs) with pathological results in 37 patients were analyzed. The SUVmax of [68 Ga]Ga-DOTA-FAPI-04 in the nonmetastatic LNs was significantly lower than that in the metastatic LNs. Regarding metastatic LN identification, the calculated optimum cut-off value of [68 Ga]Ga-DOTA-FAPI-04 SUVmax was 5.5, and the diagnostic accuracy using [68 Ga]Ga-DOTA-FAPI-04 and 2-[18F]FDG criteria was 94% and 30%, respectively (P < 0.001). For M staging, [68 Ga]Ga-DOTA-FAPI-04 identified more lesions than 2-[18F]FDG (257 vs. 139 lesions) in 14 patients with multiple metastases. Overall, the staging accuracy of [68 Ga]Ga-DOTA-FAPI-04 was better than that of 2-[18F]FDG in 52 patients with different pathological stages [43/52 (82.7%) vs. 27/52 (51.9%), P = 0.001]. CONCLUSION: Compared with 2-[18F]FDG PET/CT, [68 Ga]Ga-DOTA-FAPI-04 PET/CT demonstrated better staging performance in NSCLC patients with different pathological stages, especially those with localized disease.

Clinical Understaging, Treatment Response, and Survival Among Esophageal Adenocarcinoma Patients.

INTRODUCTION: Selecting appropriate management for patients with esophageal adenocarcinoma (EA) is predicated on accurate clinical staging information. Inaccurate information could lead to inappropriate treatment and suboptimal survival. We investigated the relationship between staging accuracy, treatment, and survival. METHODS: This was a national cohort study of EA patients in the National Cancer Data Base (2006-2015) treated with upfront resection or neoadjuvant therapy (NAT). Clinical and pathological staging information was used to ascertain staging concordance for each patient. For NAT patients, Bayesian analysis was used to account for potential downstaging. We evaluated the association between staging concordance, receipt of NAT, and survival through hierarchical logistic regression and multivariable Cox regression. RESULTS: Among 7635 EA patients treated at 877 hospitals, 3038 had upfront resection and 4597 NAT followed by surgery. Relative to accurately staged patients, understaging was associated with a lower likelihood (odds ratio [OR] 0.04 95% confidence interval [CI] 0.02-0.05) while overstaging was associated with a greater likelihood of receiving NAT (OR 1.98 [1.53-2.56]). Relative to upfront surgery, treatment of cT1N0 patients with NAT was associated with a higher risk of death (HR 3.08 [2.36-4.02]). For accurately or overstaged cT3-T4 patients, NAT was associated with a lower risk of death whether downstaging occurred (ypN0 disease-HR 0.67 [0.49-0.92]; N+ disease-HR 0.55 [0.45-0.66]) or not (ypN + disease-HR 0.78 [95% CI 0.65-0.93]). CONCLUSIONS: Clinical understaging is associated with receipt of NAT which in turn may have a stage-specific impact on patients' survival regardless of treatment response. Guidelines should account for the possibility of inaccurate clinical staging.

Understanding the association between clinical staging accuracy, treatment response, and survival among gastric cancer patients through Bayesian analysis.

BACKGROUND: Neoadjuvant therapy (NAT) improves survival among patients with locally advanced gastric cancer (GC), but it remains unclear whether its benefit is contingent on treatment response. METHODS: This is a national cohort study of stage Ib-III GC patients in the National Cancer Data Base (2006-2015) treated with upfront resection or NAT followed by surgery. Bayesian analysis was used for NAT patients to ascertain staging concordance and to account for down-staging. We used multivariable Cox regression to evaluate the association between staging concordance, treatment, response to NAT, and survival. RESULTS: The cohort included 13 340 patients treated at 1124 hospitals. Staging concordance ranged from 86.1% for cT3-4N+ to 34.7% for cT2N0 patients. Relative to accurately staged patients treated with upfront surgery, NAT was associated with a decreased risk of death if there was disease down-staging among those with cT1-2N+ (hazard ratio [HR]: 0.43 [0.30-0.61]), cT3-4N0 (HR: 0.69 [0.54-0.88]), and cT3-4N+ (HR: 0.51 [0.48-0.58]) tumors, and in the absence of down-staging among cT3-4N+ patients (HR: 0.83 [0.74-0.92]). Conversely, NAT without down-staging increased the risk of death among those with intermediate-stage disease. CONCLUSIONS: NAT is associated with improved survival for GC, but it seems to be contingent on treatment response among patients with intermediate-stage disease.

Prolonged grief disorder in DSM-5-TR: Early predictors and longitudinal measurement invariance.

OBJECTIVE: The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Text Revision includes prolonged grief disorder as a novel disorder. Prolonged grief disorder can be diagnosed when acute grief stays distressing and disabling, beyond 12 months following bereavement. Evidence indicates that elevated prolonged grief disorder symptoms in the first year of bereavement predict pervasive grief later in time; targeting early elevated grief may potentially prevent symptoms getting chronic. There is limited knowledge about the characteristics of people in the first year of bereavement who have an elevated chance of developing full prolonged grief disorder beyond the 12-month time point. This study examined these characteristics. METHODS: We used self-reported data from 306 adults who all completed questions on socio-demographic and loss-related characteristics plus a measure of prolonged grief disorder within the first year of bereavement (Wave 1; time since loss: M = 4.97, SD = 3.13 months) and again 1 year later (Wave 2; time since loss: M = 17.84, SD = 3.38 months). We examined the prevalence rates of probable prolonged grief disorder (Wave 2), measurement invariance of prolonged grief disorder symptoms between waves, and associations of socio-demographic and loss-related variables, and Wave 1 prolonged grief disorder with probable prolonged grief disorder at Wave 2. RESULTS: Regarding prevalence, 10.1% (n = 31) met criteria for probable prolonged grief disorder (Wave 2). Multigroup confirmatory factor analysis supported longitudinal measurement invariance of prolonged grief disorder symptoms. People meeting criteria at Wave 1 (except the time criterion) had a significantly increased risk of meeting criteria at Wave 2. Variables best predicting probable prolonged grief disorder at Wave 2 were prolonged grief disorder at Wave 1, lower education, loss of a child and loss to unnatural/violent causes (sensitivity = 56.67%, specificity = 98.12%, 93.92% correct classifications). CONCLUSION: People meeting criteria for prolonged grief disorder (except the time criterion) before the first anniversary of the death are at risk of full-blown prolonged grief disorder beyond this time point, particularly those who have lower education, confronted the death of a child and confronted unnatural/violent loss. Findings may inform advances in preventive bereavement care.

The accuracy of clinical neck staging for p16-positive and negative oropharyngeal cancer and its therapeutic implications.

PURPOSE: Oropharyngeal squamous cell carcinoma (OPSCC) may be treated with primary surgery or primary (chemo)radiation. While surgery with concurrent neck dissection provides definitive pathological staging of the neck, non-surgical treatment relies on clinical staging for treatment planning. To assess the accuracy of clinical neck staging, we compared clinical to surgical staging after primary surgery in patients with p16-negative and p16-positive OPSCC. METHODS: Retrospective analysis of clinical, pathological, and oncologic outcome data of patients with OPSCC treated with primary surgery and bilateral neck dissection. Clinical and pathological nodal status were compared for p16-negative and p16-positive patients. Patients with occult metastatic disease were analyzed in detail. RESULTS: 95 patients were included. 60.5% of p16-negative patients and 66.6% of p16-positive patients had pathologically confirmed metastatic neck disease. p16-positive patients had improved 24-month recurrence-free survival compared to p16-negative patients at 93.3% vs. 69.6%. Pathological N-status differed from clinical N-status in 36.8% of p16-negative patients vs. 31.6% of p16-positive patients. Occult metastatic disease was more common in p16-negative patients at 18.4% vs. 8.8% for p16-positive patients. Clinical detection sensitivity for extranodal extension was low overall; sensitivity was 27.3% and specificity was 91.6% for p16-negative patients vs. 61.5% and 80.0% for p16-positive patients, respectively. CONCLUSION: Our data show a considerable degree of inaccuracy of clinical neck staging results in all OPSCC patients which needs to be taken into consideration during therapy planning. For p16-positive patients, these findings warrant attention in the context of therapy deintensification to avoid undertreatment.