bluuebunny/crossref_metadata_2025 huggingface dataset:
Validity of the I‑FEED classification in assessing postoperative gastrointestinal impairment in patients undergoing elective lumbar spinal surgery with general anesthesia: a prospective observational study
Authors: Wu Chun-Yu , Lai Chih-Jun , Xiao Fu-Ren , Yang Jen-Ting , Yang Shih-Hung , Lai Dar-Ming , Tsuang Fon-Yih
Published: June 2024

Background

The I-FEED classification, scored 0–8, was reported to accurately describe the clinical manifestations of gastrointestinal impairment after colorectal surgery. Therefore, it is interesting to determine whether the I-FEED scoring system is also applicable to patients undergoing lumbar spine surgery.

Methods

Adult patients undergoing elective lumbar spine surgery were enrolled, and the I-FEED score was measured for 4 days after surgery. The I-FEED scoring system incorporates five elements: intake (score: 0, 1, 3), feeling nauseated (score: 0, 1, 3), emesis (score: 0, 1, 3), results of physical exam (score: 0, 1, 3), and duration of symptoms (score: 0, 1, 2). Daily I-FEED scores were summed, and the highest overall score is used to categorize patients into one of three categories: normal (0–2 points), postoperative gastrointestinal intolerance (POGI; 3–5 points), and postoperative gastrointestinal dysfunction (POGD; 6 + points). The construct validity hypothesis testing determines whether the I-FEED category is consistent with objective clinical findings relevant to gastrointestinal impairment, namely, the longer length of hospital stay (LOS), higher inhospital medical cost, more postoperative gastrointestinal medical treatment, and more postoperative non-gastrointestinal complications.

Results

A total of 156 patients were enrolled, and 25.0% of patients were categorized as normal, 49.4% POGI, and 25.6% POGD. Patients with higher I-FEED scores agreed with the four validity hypotheses. Patients with POGD had a significantly longer length of hospital stay (1 day longer median stay; p = 0.049) and more inhospital medical costs (approximately 500 Taiwanese dollars; p = 0.037), and more patients with POGD required rectal laxatives (10.3% vs. 32.5% vs. 32.5%; p = 0.026). In addition, more patients with POGD had non-gastrointestinal complications (5.1% vs. 11.7% vs. 30.0%; p = 0.034).

Conclusion

This study contributes preliminary validity evidence for the I-FEED score as a measure for postoperative gastrointestinal impairment after elective lumbar spine surgery.
Emilin2 marks the target region for mesenchymal cell accumulation in bone regeneration
Authors: Qing Yifan , Ono Takehito , Kohara Yukihiro , Watanabe Atsushi , Ogiso Noboru , Ito Masako , Nakashima Tomoki , Takeshita Sunao
Published: June 2024

Background

Regeneration of injured tissue is dependent on stem/progenitor cells, which can undergo proliferation and maturation processes to replace the lost cells and extracellular matrix (ECM). Bone has a higher regenerative capacity than other tissues, with abundant mesenchymal progenitor cells in the bone marrow, periosteum, and surrounding muscle. However, the treatment of bone fractures is not always successful; a marked number of clinical case reports have described nonunion or delayed healing for various reasons. Supplementation of exogenous stem cells by stem cell therapy is anticipated to improve treatment outcomes; however, there are several drawbacks including the need for special devices for the expansion of stem cells outside the body, low rate of cell viability in the body after transplantation, and oncological complications. The use of endogenous stem/progenitor cells, instead of exogenous cells, would be a possible solution, but it is unclear how these cells migrate towards the injury site.

Methods

The chemoattractant capacity of the elastin microfibril interface located protein 2 (Emilin2), generated by macrophages, was identified by the migration assay and LC–MS/MS. The functions of Emilin2 in bone regeneration were further studied using Emilin2–/– mice.

Results

The results show that in response to bone injury, there was an increase in Emilin2, an ECM protein. Produced by macrophages, Emilin2 exhibited chemoattractant properties towards mesenchymal cells. Emilin2–/– mice underwent delayed bone regeneration, with a decrease in mesenchymal cells after injury. Local administration of recombinant Emilin2 protein enhanced bone regeneration.

Conclusion

Emilin2 plays a crucial role in bone regeneration by increasing mesenchymal cells. Therefore, Emilin2 can be used for the treatment of bone fracture by recruiting endogenous progenitor cells.
Source-independent Q-compensated viscoacoustic least-squares reverse time migration
Authors: Liu Wei , Shi Ying , Wang Ning , Wang Weihong , Fang Jinwei
Published: June 2024

The strong viscosity of the subsurface introduces amplitude absorption and phase-velocity dispersion. Incorrect compensation of the inherent attenuation (the strength of the seismic attenuation can be quantified by the inverse of the quality factor Q, which is defined as [Formula: see text] times the ratio of the stored energy to the lost energy in a single cycle of deformation) can significantly affect imaging quality. Although Q-least-squares reverse time migration ( Q-LSRTM) allows for the compensation of attenuation effects during the iterations, the traditional [Formula: see text]-norm minimization, which is highly sensitive to the source wavelet, poses a challenge in accurately estimating the source wavelet from the field data. Thus, we develop a source-independent Q-LSRTM, in which a convolutional objective function is introduced to replace the [Formula: see text]-norm constraint to mitigate the source wavelet effect. According to the Born approximation, we first linearize the constant-order decoupled fractional Laplacian viscoacoustic wave equation to derive the demigration operator and then construct the corresponding adjoint equation and gradient based on the convolutional objective function, iteratively estimating the reflectivity images. Our method relaxes the sensitivity to the wavelet compared with the conventional [Formula: see text]-norm scheme due to the convolutional objective function, which has the ability to construct the same new source for simulated and observed data. Numerical tests on a layered model, the Marmousi model, and field data demonstrate that our source-independent Q-LSRTM enables us to obtain high-quality reflectivity images even when using incorrect source wavelets.
Reviews
Authors: Aitken Julie
Published: June 2024

World Atlas of Submarine Gas Hydrates in Continental Margins, edited by Jürgen Mienert et al., 2022
Geoscientists Around the Globe
Authors:   The SEG JEDI Committee
Published: June 2024

Coordinated by members of SEG's Justice, Equity, Diversity, and Inclusion (JEDI) Committee, TLE's Geoscientists Around the Globe department features geoscientists from technically, geographically, and culturally diverse backgrounds. In this installment, JEDI Committee member Ellie Ardakani interviews Teyyuba Adigozalova, a geophysicist at bp.
Unlocking the Potential: Biomarkers of Response to Antibody-Drug Conjugates
Authors: Ascione Liliana , Guidi Lorenzo , Prakash Ajay , Trapani Dario , LoRusso Patricia , Lou Emil , Curigliano Giuseppe
Published: June 2024

Antibody-drug conjugates (ADCs) have reshaped the cancer treatment landscape across a variety of different tumor types. ADCs' peculiar pharmacologic design combines the cytotoxic properties of chemotherapeutic agents with the selectivity of targeted therapies. At present, the approval of many ADCs used in clinical practice has not always been biomarker-driven. Indeed, predicting ADCs' activity and toxicity through the demonstration of specific biomarkers is still a great unmet need, and the identification of patients who can derive significant benefit from treatment with ADCs may often be uncertain. With the lack of robust predictive biomarkers to anticipate primary, intrinsic resistance to ADCs and no consolidated biomarkers to aid in the early identification of treatment resistance (ie, acquired resistance), the determination of precise biologic mechanisms of ADC activity and safety becomes priority in the quest for better patient-centric outcomes. Of great relevance, whether the target antigen expression is a determinant of ADCs' primary activity is still to be clarified, and available data remain quite controversial. Antigen expression assessment is typically performed on tissue biopsy, hence only providing information on a specific tumor site, therefore unable to capture heterogeneous patterns of tumor antigen expression. Quantifying the expression of the target antigen across all tumor sites would help better understand tumor heterogeneity, whereas molecularly characterizing tumor-intrinsic features over time might provide information on resistance mechanisms. In addition, toxicity can represent a critical concern, since most ADCs have a safety profile that resembles that of chemotherapies, with often unique adverse events requiring special management, possibly because of the differential in pharmacokinetics between the small-molecule agent versus payload of a similar class (eg, deruxtecan conjugate–related interstitial lung disease). As such, the identification of robust predictive biomarkers of safety and activity of ADCs has the potential to improve patient selection and enrich the population of patients most likely to derive a substantial clinical benefit, especially in those disease settings where different ADCs happen to be approved in competing clinical indications, with undefined biomarkers to make precise decision making and unclear data on how to sequence ADCs. At this point, the identification of clinically actionable biomarkers in the space of ADCs remains a top research priority.
RMS13: A phase II trial using risk adapted focal proton beam radiation and/or surgery with the addition of maintenance chemotherapy in intermediate risk rhabdomyosarcoma.
Authors: Gartrell Jessica , Pappo Alberto S. , Li Yimei , Patni Tushar , Indelicato Daniel J. , Federico Sara Michele , Stewart Elizabeth , Tinkle Christopher L , Helmig Sara , Lucas John Thomas , Bishop Michael W. , McCarville Mary B , Albritton Karen H. , Krasin Matthew J.
Published: June 2024

10008

Background: European trials have demonstrated improved outcomes in SIOP high-risk/COG intermediate risk (IR) rhabdomyosarcoma (RMS) when 6 months of maintenance therapy (MTC) was added to ifosfamide, vincristine (VCR), dactinomycin (DAC) +/-doxorubicin chemotherapy. The effectiveness of MTC integrated with VCR, DAC and cyclophosphamide (CYC), standard North American chemotherapy, remains unclear. Methods: RMS13 is a phase II multicenter trial evaluating the safety and efficacy of risk adapted proton radiation therapy (RT) and the addition of MTC in patients with IR RMS (embryonal stage 1, Group III non-orbit, and stage 3 Group I, II were not eligible for MTC). Patients received 12 cycles of VCR (1.5mg/m2 weekly), DAC (0.045mg/kg q3weeks), and CYC (1200mg/m2 q3weeks) (VAC) followed by MTC with 4 cycles of oral CYC (50mg/m2 daily), bevacizumab (15mg/kg) q3wks, and sorafenib (90mg/m2 bid) (CBvSor). RT was prescribed based on local tumor status at the time of RT (Table 1). Five-year disease-free survival (DFS) using the Kaplan-Meier method and the cumulative incidence (CI) of primary site local failure (LF) was described. Results: 46 patients were enrolled (Table 1). One patient refused further therapy and was removed from the analysis. 5-year DFS for the entire cohort was 67.5% with a median follow up of 54 mo. The trial was halted since < 75% of enrolled patients received all prescribed CBvSor MTC. Of the 35 who were eligible for MTC, 24 initiated MTC and 18 completed protocol-directed MTC. Three pts received vinorelbine/CYC MTC after enrollment was stopped. Reasons for not completing CBvSor MTC included: progression prior (6), toxicity (5), refusal (3). The 5-year DFS for the 24 patients that started cycle 3 was 70.3%. When limited to patients classified as high-risk in RMS2005 trial, the 5-year DFS was 81.4%. No patients experienced LF after margin negative surgery. The CI of LF was: 0% following 36GyRBE RT for microscopic residual disease, 8% for patients with unresected tumors < 5cm receiving standard dose RT (50.4GyRBE), and 10% for patients with unresected tumors > = 5cm receiving dose escalated RT (59.4GyRBE). 5/6 patients with alveolar N1 disease recurred. Conclusions: Local control with risk adapted dose-escalated RT was excellent in IR patients. Those with nodal involvement fared poorly. While 4-cycles of MTC with CBvSor was not feasible, those who underwent at least 3 cycles experienced enhanced DFS outcomes, aligning with the positive results seen in other trials incorporating MTC. Clinical trial information: NCT01871766 . [Table: see text]
Efficacy and safety of the use of dinutuximab in newly diagnosed or relapse high risk neuroblastoma: Single arm systematic review and meta-analysis.
Authors: Escalante Romero Lorena , Celso Davi Said Gonçalves , Silva Isadora Mamede Mendes da , Reis Pedro Cotta Abrahão , Dacoregio Maria Inez , Stecca Carlos , Monteiro Caran Eliana Maria
Published: June 2024

10044

Background: Patients with high-risk Neuroblastoma have a poor prognosis, with 43% experiencing a 3-year survival rate in newly diagnosed cases and a 21% 1-year event-free survival in relapsed patients. Dinutuximab, an immunotherapy targeting anti-disialoganglioside (GD2), emerges as a promising treatment for high-risk Neuroblastoma. This single arm meta-analysis aims to assess the efficacy and safety of dinutuximab, providing insights into its impact on survival rates among neuroblastoma patients. Methods: We systematically searched Pubmed, Cochrane and EMBASE for clinical trials between 1988 to 2023 utilizing Dinutuximab (ch14.18 or ch14.18/CHO) in patients with newly diagnosed or relapsed/refractory high-risk neuroblastoma. We pooled the prevalence and the 95% confidence intervals (CI) for the outcomes of interest: overall survival (OS), event-free survival (EFS) and progression-free survival (PFS), objective response rate (ORR), and treatment-emergent adverse events (TEAE). Heterogeneity was assessed using I² analysis and all statistical analyses were employed using R software version 4.3.2 and a random-effects model. Results: The analysis included 2214 patients from 13 clinical trials, comprising four phase III trials and six phase II. Six studies included Interleukin 2 (IL-2). Among the patients, 364 (16.5%) had relapsed or refractory disease. Dinutuximab was applied as post-consolidation treatment in 1809 patients (81.1%). The age of patients ranged from 1 to 21 years. In a pooled analysis, the 3-year OS rate was 69% (CI 0.62-0.76; I² = 85%), and the 3-year EFS rate was 61% (CI 0.52-0.69; I² = 77%). In the group of newly diagnosed patients, the 3-year EFS rate was 62% (CI 0.58-0.66; I² = 52%) and 3-year OS rate of 74% (CI 0.69-0.79; I² = 71%). Among patients with relapse, there was a 3-year OS rate of 57% (CI 0.50-0.64; I² = 0%). The overall ORR was 47% (CI 0.37-0.57; I² = 69%), of which 38 newly diagnosed patients using Dinutuximab during induction chemotherapy showed an ORR of 86%. TEAEs of grade ≥ 3 were 70% (CI 0.44-0.88; I² = 94%), and in the subgroup without IL-2 use, it was 43% (CI 0.29-0.57; I² = 85%). Conclusions: This single-arm meta-analysis suggests that both newly diagnosed or relapsed/refractory high-risk Neuroblastoma patients benefit from Dinutuximab, with a promising impact on 3-year OS and EFS. Dinutuximab appears to be a safer option; however, concomitant use of IL2 is associated with a higher rate of adverse effects.
Evaluation of kidney function and body composition in adult survivors of unilateral, non-metastatic, non-syndromic Wilms tumor: A report from the St. Jude Lifetime Cohort Study.
Authors: Green Daniel M. , Li Kendrick , Kaste Sue C. , Ness Kirsten K. , Krasin Matthew J. , Xie Lu , Wilson Carmen L , Srivastava Deo Kumar , Davidoff Andrew M. , Zahr Rima S , Taneja Siddhant , Shelton Kyla C. , Lanctot Jennifer Q. , Dixon Stephanie B , Ehrhardt Matthew J. , Mulrooney Daniel A. , Goodenough Chelsea Goodliffe , Armstrong Gregory T. , Robison Leslie L. , Hudson Melissa M.
Published: June 2024

10064

Background: The relationships among treatment exposures, body composition and estimated glomerular filtration rate (eGFR) in adult survivors of childhood have not been well studied. Methods: We evaluated body composition with dual energy x-ray absorptiometry (DXA) and eGFR with the Kidney Disease International Global Outcomes (KDIGO) 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) in 149 adults previously treated for non-syndromic, non-metastatic, unilateral Wilms tumor at St. Jude Children’s Research Hospital between 1964 and 2004 with chemotherapy and with [(whole abdomen (WA) radiation therapy (RT) – 41 patients; median dose 12.5 Gray (Gy), Interquartile Range (IQR) 12.5 – 20.0 Gy); (hemiabdomen (HA) RT – 30 patients; median dose 12.0 Gy, IQR 10.8 – 20.1 Gy)] or without (78 patients) RT. z-scores for DXA variables were calculated using data from the National Health and Nutrition Survey (1). Results: The study population [56 males (37.6%), 109 whites (73.2%)] was a median of 3.1 years of age at diagnosis (IQR: 1.7-4.3) and 23.4 years at evaluation (IQR: 23.4-35.5). Relative total and relative trunk lean mass, and eGFR were significantly decreased among those who received WART compared to unirradiated patients. Linear regression demonstrated that WART was significantly associated with a lower eGFR (p = 0.012) and higher value of creatinine (p = 0.013). Conclusions: Relative total and relative trunk lean mass, and eGFR are decreased in survivors of unilateral, non-metastatic, non-syndromic WT following WART. Although eGFR was in the normal range, eGFR may be inaccurate due to loss of lean mass. Assessments using non-secreted molecules may more accurately measure the magnitude of kidney function loss among WART treated WT survivors. 1. PLoS ONE 2009;4(9):e7038. [Table: see text]
Mapping aging phenotypes in childhood cancer survivors: A report from the St. Jude Lifetime Cohort.
Authors: Ness Kirsten K. , Mirzaei Salehabadi Sedigheh , Webster Rachel T , Jacola Lisa M , Salerno Elizabeth A , Huang I-Chan , Brinkman Tara M. , Ehrhardt Matthew J. , Krull Kevin R. , Mori Motomi , Srivastava Deokumar , Armstrong Gregory T. , Wang Zhaoming , Hudson Melissa M.
Published: June 2024

10069

Background: Childhood cancer survivors experience accelerated aging manifest as physical, cognitive and/or emotional impairments. Aging populations respond to behavioral interventions that address impairment combinations. We aimed to identify and characterize phenotypes (classes) of physical, cognitive and emotional impairments in childhood cancer survivors to inform targets for future intervention. Methods: Factor analysis using St. Jude Lifetime Cohort data (N=4051, 52.2% male, mean [SD] age at diagnosis 8.7 [5.7], assessment 33.9 [10.1] years) generated 9 impairment domains (Table) using 40 items from the Neurocognitive Questionnaire, Brief Symptom Inventory 18 and NHIS Health Status/Limitation of Activities. Latent class analysis estimated impairment patterns and class membership probabilities. Descriptive statistics characterized survivors by class for deficit accumulation index (DAI) score (range 0-1, >0.25 frail), Fried Frailty (FF) score (range 0-5, ≥3 frail), diagnosis and treatment exposures. Logistic regression comparing emotional or cognitive impairment class to the physical impairment class examined associations between survivor characteristics and class membership, adjusting for diagnosis and assessment ages, sex and race/ethnicity. Results: Three classes (phenotypes) differentiated survivors reporting only physical from those reporting both physical and cognitive or emotional impairments. Mean [SD] DAI (cognitive 0.40 [0.10], emotional 0.56 [0.16], physical 0.16 [0.11]) and FF scores (cognitive 1.5 [1.0], emotional 1.8 [1.0], physical 0.9 [0.9]) were highest in the emotional impairment class. Compared to solid tumor survivors (17.1%), brain tumor (33.7%, OR 3.5; 95% CI 2.7-4.4) and leukemia (21.7%, OR 1.5; 95% CI 1.2-1.8) survivors were more likely to be in the cognitive impairment class. Leukemia (OR 1.4; 95% CI 1.1-1.7) and lymphoma (OR 1.4; 95% CI 1.1-1.9) diagnoses increased risk for emotional impairment class membership. Cranial radiation was associated with cognitive (OR 1.8; 95% CI 1.5-2.2) or emotional (OR 1.3; 95% CI 1.1-1.6) impairment class membership. Chest radiation (1.4; 95% CI 1.2-1.7) was associated with emotional impairment class membership. Conclusions: These data provide foundational information for development and testing of targeted behavioral interventions to remediate accelerated aging in survivors. [Table: see text]
Social support dynamics within parent-AYA cancer survivor dyads in a rural, socioeconomically disadvantaged, majority Hispanic/Latino region.
Authors: Lewinsohn Rebecca M. , Benedict Catherine , Smith Mary , Boynton Heidi , Schapira Lidia , Smith Stephanie M
Published: June 2024

10071

Background: Childhood cancer survivors and their parents often face psychological, financial, and informational challenges as survivors transition to adolescent/young adult (AYA) age, which can be exacerbated by socioeconomic disparities. Social support can positively impact the trajectory of AYA survivors and their parents by facilitating post-traumatic growth and wellbeing and reducing psychological distress. The aim of this study was to examine social support dynamics within AYA-parent dyads by comparing their support needs and gaps. Methods: This qualitative study was conducted in collaboration with a community-based organization (CBO) serving a predominately socioeconomically disadvantaged, Hispanic/Latino (H/L), and rural population of families affected by childhood cancer in California. English- and Spanish-speaking AYA childhood cancer survivors (≥15 years old, ≥5 years from diagnosis) and parents were interviewed. Transcripts were analyzed qualitatively using applied thematic analysis. Results: Seven AYA-parent dyads (6 H/L) participated in the study. AYAs (6 male, 1 female) were median (min-max) age 19 (16-23) and 14 years post diagnosis (6-17). Parents (1 male, 6 female) were predominantly Spanish-speaking (5/7). Forms of social support fell into emotional, instrumental (i.e. tangible assistance such as financial help), and informational domains. Although family and faith were shared sources of emotional support for parents and AYAs, parents were more likely to discuss fractured family support structures and unmet emotional needs. In contrast AYAs universally identified their parents as consistent sources of emotional support. Parents also more commonly discussed gaps in instrumental support, which were exacerbated by being a single parent and lacking a local extended family network after immigrating to the United States. Parents were frequently the primary source of informational support for their children and AYAs often lacked knowledge regarding their cancer diagnosis and treatment course. Two AYAs expressed ambivalence about receiving more survivorship-focused information due to it bringing up negative emotions around fear of recurrence. Parents frequently expressed worry about their child’s readiness to transition to adult care. Conclusions: Parents experienced gaps in emotional and instrumental social support that were not noted by AYAs, suggesting that parents protected their children from these experiences. Parents continued to serve as primary sources of informational support for AYAs even as they transitioned out of pediatric care. Our findings demonstrate the opportunity to build upon supportive parent-AYA relationships through dyad-focused education and counseling, which may improve readiness to transition to adult-focused survivorship care.
Cost-effectiveness of single-day intravenous fosaprepitant versus three-day oral aprepitant anti-emetic regimen in pediatric patients receiving highly-emetogenic chemotherapy.
Authors: Sra Manraj Singh , Abdul Rasheed Azgar , Ganguly Shuvadeep , Kumar Santosh , Sharma Priya , Pillai Ashwati S , Sharma Swetambri , PUSHPAM DEEPAM , Bakhshi Sameer
Published: June 2024

10075

Background: The non-inferiority of single-dose fosaprepitant to a three-day oral aprepitant-based anti-emetic regimen for pediatric patients receiving high emetogenic chemotherapy (HEC) has not been demonstrated. The cost-effectiveness of these regimens with respect to each other in India and the United States (US) is unknown. Methods: Individual patient data from an investigator-initiated, open-label, non-inferiority randomized control trial was used to estimate health states. The total costs and quality-adjusted life years (QALY) were calculated from the patient's perspective in India and the US. The incremental-cost utility ratio (ICUR) and net-monetary benefit (NMB) were calculated. One-way sensitivity analysis was done by varying the cost of medications, hospitalization and utility values by ±25%. Results: The fosaprepitant arm had a total QALY of 0.0116 compared to 0.0118 in the aprepitant arm. The use of fosaprepitant led to an incremental cost of $14.21 in India and a cost reduction of $193.81 in the US. The total cost of medication in the fosaprepitant arm was higher in India and lower in the US compared to the aprepitant arm. The cost of hospitalisation was lower in the fosaprepitant in both India and the US. The ICUR was -$59,974.86/QALY in India and $817,737.23/QALY in the US. The ICUR for India was located in the north-west quadrant of the cost-effectiveness plane, for the US it was located in the south-west quadrant below the willingness the pay threshold for the US. The ICUR estimate was most sensitive to the cost of fosaprepitant in India and the utility value of the complete protection health state in the US. Conclusions: Fosaprepitant was not found to be cost-effective versus aprepitant in India, comparatively it was cost-saving and cost-effective in the US. These findings highlight the necessity of region-specific considerations when evaluating the cost-effectiveness of anti-emetic regimens. [Table: see text]
Effects of HPV vaccination on the development of HPV-related cancers: A retrospective analysis of a United States-based cohort.
Authors: DeKloe Jefferson , Urdang Zachary David , Martinez Outschoorn Ubaldo E. , Curry Joseph M.
Published: June 2024

10507

Background: Several studies have shown the efficacy of the Human Papillomavirus (HPV) vaccine in reducing the risk of cervical cancer. Given the recent introduction of the HPV vaccine, there has been limited evidence linking vaccination to a decreased likelihood of developing other HPV-related cancers. Methods: A retrospective cohort study was conducted using a patient population selected from the TriNetX United States Collaborative Network. Patients 9-39 years old attending medical encounters where any vaccine was administered between 1/1/2010 and 12/31/2023 were divided into two cohorts: patients vaccinated for HPV at least five years prior and those no history of HPV vaccination. Outcomes were malignancies at the following sites: Head and Neck (HNC), Cervix, Anus & Anal Canal, Penis, Vulva, and Vagina. Patients with no prior history of cervical dysplasia undergoing Pap smear were observed for atypical cytology. Propensity score matching was performed to match cohorts for age, race/ethnicity, tobacco use, and BMI. Results: Males vaccinated for HPV (n = 760,540) were at decreased odds for HPV-related cancers (odds ratio (OR) = 0.46, 95 % confidence interval (CI) = 0.29-0.72, p-value = 0.001). This finding was primarily driven by a significant reduction in HNC (OR = 0.44, CI = 0.26-0.73, p = 0.0016). Females vaccinated for HPV (n = 945,999) had lower odds for cervical (OR = 0.71, CI = 0.52-0.96, p-value = 0.027) cancers and HPV-related cancers overall (OR = 0.73, CI = 0.57-0.94, p = 0.013). Odds of HNC (OR = 0.67, CI = 0.42-1.1, p = 0.10) and Vulvar/Vaginal cancer (OR = 1.67, CI = 0.81-3.41, p = 0.16) were not significantly different in vaccinated females compared to controls. Vaccinated females were less likely to develop High Grade Squamous Intraepithelial Lesions (HGSIL), (OR = 0.44, CI = 0.30-0.65, p < 0.0001), and Carcinoma In-Situ(OR = 0.422, CI = 0.25-0.72, p = 0.002). Conclusions: These results suggest early evidence of efficacy in the vaccine in preventing the development of several types of malignancies and pre-malignant dysplasia caused by HPV. [Table: see text]
Incidence trends of advanced breast cancer in an era of its routine screening in the United States: A population-based study.
Authors: Ilerhunmwuwa Nosakhare Paul , Uche Ifeanyi , Wasifuddin Mustafa
Published: June 2024

10523

Background: One of the purposes of routine screening for cancers is to delay the time of diagnosis of the late or advanced stages of the disease. Breast cancer screening is recommended for women aged 40 years and above. Over 70% of women reported receiving mammograms in the last two years between 2001 and 2020. Despite widespread screening, the impact on incidence trends of advanced breast cancer (aBC) in real-world settings in the last two decades is largely unknown. Methods: This population-based study identified adults aged 40–74 with regional/distant stage breast cancer (advanced) diagnosed between 2004 and 2020, using the Surveillance, Epidemiology, and End Results, 17 Research Plus registries. Age-adjusted incidence rates (AAIR) per 100,000 persons were extracted for aBC, with rates age-adjusted to the US standard population. The annual percentage change (APC) of the age-standardized incidence rate was estimated with the Joinpoint regression program. The APC was used to compare incidence trends stratified by age (40-54 vs. 55-74 years), race/ethnicity, and area of residence. Results: A total of 194,946 cases of aBC were diagnosed between 2004 and 2020; 120 257 (61.7%) were Non-Hispanic White (NHW), 28 585 (14.7%) were Hispanics, 25 691 (13.2%) were Non-Hispanic Black (NHB), 18 192 (9.3%) were Non-Hispanic Asian or Pacific Islander (NHAPI), 1326 (0.7%) were Non-Hispanic American Indians/Alaska Natives (NHAIA), and 895 (0.5%) were of unknown race/ethnicity. From 2004 to 2020, the overall AAIR of aBC showed an increase (APC, 0.2%: 0.00 – 0.40), with a notable rise in NHAPI (APC, 1.43%: 1.00 – 1.90) and Hispanics (APC of 0.66% (0.24 – 1.15), while remaining stable in other racial groups. Additionally, the AAIR increased among individuals aged 40-54 years (APC, 0.58%: 0.38 – 0.79) but was stable in those between 55-74 years. Regarding the area of residence, there was a significant increase in non-metropolitan areas (APC, 0.65%: 0.38 – 0.93), contrasting with no significant change in metropolitan areas. Conclusions: Despite widespread breast cancer screening, the occurrence of aBC has persistently increased, especially among individuals aged 40 to 54 years, NHAIA, and in non-metropolitan areas. Further studies are needed to establish the underlying reasons for these observed trends.
Differences in shared decision-making and prostate cancer screening by sexual orientation and race/ethnicity.
Authors: Nguyen Kirsten , Gonzales Gilbert
Published: June 2024

10525

Background: There are well-documented disparities among racial and sexual minorities in prostate cancer screening uptake and shared-decision making (SDM) conversations. However, it is unclear how racial/ethnic identity and sexual orientation interact to affect prostate-specific antigen (PSA) testing uptake. Methods: Data came from the 2018-2022 Behavioral Risk Factor Surveillance Survey (BRFSS). Outcomes were survey responses to questions about engagement in SDM and PSA testing uptake. The sample included 88,365 heterosexual (HS) men and 2,562 sexual minority (SM) men ages 55 to 69. Data were stratified by race/ethnicity and survey-weighted logistic regression models analyzed the association between sexual orientation and outcomes. Models controlled for age, relationship status, education, household income, insurance status, having a usual source of care, and region. Results: White SM men were more likely to have discussed disadvantages of PSA testing with their healthcare provider [odds ratio (OR)=1.407; p<0.001] and to have undergone PSA testing [OR=1.320; p<0.001] compared to White HS men. Asian SM men were more likely to have had discussions about PSA testing [OR=4.470; p<0.05]; to have discussed advantages [OR=4.596; p<0.05]; to have been recommended PSA testing [OR=4.836; p<0.05] and to have undergone PSA testing [OR=4.401; p<0.001] compared to Asian HS men. Black SM men were more likely to undergo screening because of an issue or a reason besides routine screening [OR=1.073, p<0.05] compared with Black HS men. Hispanic SM men were more likely to have undergone screening as part of a routine checkup [OR=4.2, p<0.001] compared with Hispanic HS men. There were no sexual orientation differences in PSA screening or SDM among American Indian or Native Alaskans. Conclusions: Differences in PSA testing uptake and SDM by sexual orientation vary by race/ethnicity. Further research is needed to study the factors affecting PSA testing uptake and SDM among sexual minority men of different racial/ethnic groups. [Table: see text]
Association of polygenic-based breast cancer risk prediction with patient management.
Authors: Johansen Taber Katie , Hughes Elisha , Gutin Alexander , DeHart Brady , Becker Laura , Jasper Jeff , Ratzel Sarah , Miller Claire , Chawla Devika , Morin Pamela , Certa Julia M , Kurian Allison W.
Published: June 2024

10527

Background: Guidelines recommend individuals with ≥20% lifetime risk of breast cancer (BC) undergo enhanced management, including annual screening mammography (SM) as early as age 30, annual breast MRI, and genetic counseling (GC). Lifetime BC risk can be estimated using a validated risk model, such as Tyrer-Cuzick (TC). A risk predictor that combines TC with a polygenic risk score (“combined risk score” or CRS) significantly improves risk prediction over TC alone. Little is known about how clinicians manage patients based on CRS. Here, we describe management following receipt of CRS results. Methods: De-identified administrative claims data from the Optum Labs Data Warehouse were linked with de-identified TC and CRS results originally provided to ordering clinicians. Patients were divided into four subgroups based on their lifetime risk predicted by CRS and by TC alone (high risk: ≥20%, average risk: <20%): A (CRS-high/TC-high), B (CRS-high/TC-avg), C (CRS-avg/TC-high), and D (CRS-avg/TC-avg). Patient management claims were compared 360 days before and after the CRS test date and differences evaluated with McNemar’s test. Differences in post-test management were analyzed using multivariable logistic regression with adjustment for clinical factors. Results: Before receiving risk results, 11.9%, 7.7%, 8.8%, and 5.0% of patients in A, B, C, and D received a SM before age 40, respectively; 3.4%, 2.6%, 2.3%, and 0.9% received an MRI, respectively; and 4.3%, 4.7%, 6.0%, and 3.6% received GC, respectively. After receiving risk results, SM in those under age 40 significantly increased 1.6-2.2-fold in A, B, and C; MRI significantly increased 4.7-5.6-fold in A, B, and C; and GC significantly increased 1.9-2.3-fold in A and B. SM, MRI, and GC did not increase in D. Prophylactic mastectomy occurred in only 0.17% of all patients after receiving results. After adjustment for confounders, those in A, B, and C were 3.8-5.2 times more likely to undergo SM; 11.6-23.1 times more likely to undergo MRI; and 2.0-2.9 times more likely to undergo GC, compared to those in Group D (all p<0.001). Conclusions: Patients with a ≥20% lifetime risk for BC were more likely to undergo enhanced management compared to those with a lifetime risk <20%, regardless of whether their risk was based on the CRS or on TC. These results suggest that clinicians recommended management aligned with guidelines for those with ≥20% lifetime risk, even when such risk was predicted by the CRS. [Table: see text]
Are cancer screening recommendations from top US cancer centers concordant with the USPSTF guidelines?
Authors: Wright Kristin , Shkabari Brian , Booth Christopher M. , Knopf Kevin B. , Gyawali Bishal
Published: June 2024

10535

Background: The USPSTF is an independent volunteer organization of multi-disciplinary national experts in disease prevention that publishes evidence-based non-binding recommendations for screening diseases, including cancer. Herein we assessed the congruence of cancer screening recommendations between the USPSTF and the Top 10 US Cancer Centers (as per the U.S News and World Report). Methods: This cross-sectional study compared the published screening recommendations from the Top 10 US Cancer Centers for colorectal (CRC), lung (LC), cervical (CC), prostate (PC), and breast cancers (BC) in average risk patients, to those of the USPSTF. The variables of interest included: screening tests, recommendation direction (for/against), strength, frequency, age of start, age of end, and discussion about risks and benefits. Data extraction was done by 2 authors and discrepancies resolved by mutual consensus and discussion with a third author. Results: We demonstrate the differences between the screening recommendations from the Top 10 Cancer Centers relative to those from the USPSTF (Table). Conclusions: Our study found significant variability between the screening recommendations from the 2022-2023 USNWR top 10 cancer centers and the evidence-based USPSTF guidelines for BC, PC, CC, and CRC. The recommendations for LC were overall in line with those of the USPSTF. The discordance was almost always in the direction of the cancer centers recommending more screening beyond the USPSTF’s recommendations, and often without discussion of potential risks and harms. This inconsistency could create confusion to the public, and therefore, a consistent messaging across the cancer centers congruent with the USPSTF recommendations and including a nuanced discussion of benefits and risks may be in the best public health interest.[Table: see text]
Evaluation of cost-effective multiple cancer early detection with extremely low coverage whole genome sequencing from plasma.
Authors: Wu Wendy , Bai Jian , Wang Siqi , Yang Hao , Sun Fuming , Zheng Lu , Lu Di , Dong Xiaoying , Feng Siyang , Cai Kaican , Chen Kezhong , Yang Fan , Wang Hongyang , Chen Lei
Published: June 2024

10538

Background: Cancer continues to be a significant global health concern, with approximately 19.3 million new cases diagnosed and 10.0 million cancer-related deaths reported in 2020. Multi-cancer early detection (MCED) test using the peripheral blood offers a great opportunity to improve the current cancer screening tests with better performance and benefit-to-harm balance. Methods: Here we introduce a novel MCED test called HIFI-PROF, which utilizes extremely low pass whole-genome sequencing (median coverage of 0.6X) to create a multi-dimensional fragmentation signatures model through machine learning approach. HIFI-PROF was developed to detect and localize six types of cancer (colorectal, pancreas, liver, lung, esophagus and gastric cancer). Results: The study included a total of 1,487 participants, comprising 235 colorectal cancers, 227 pancreatic cancers, 150 liver cancers, 125 lung cancers, 107 esophageal cancers, 106 gastric cancers and 537 healthy volunteers. Most of the cancer cases were I/II stage patients (stage I: 38%, stage II: 35%, stage III: 23%, stage IV: 4%). The participants, stratified by age and clinical status, were divided into two sets: a training set (n=1,079) and a validation set (n=408).HIFI-PROF exhibited an excellent performance in the early detection of multiple cancer types, achieving a sensitivity of 87.58% at a specificity of 99.09% and identifying the tissue of origin (TOO) with an accuracy of 81.99%. The sensitivity rates for detecting cancer at different stages were also promising, with a sensitivity of 84.62% for stage I, 85.59% for stage II, 89.61% for stage III and 92.86% for stage IV. Conclusions: These results highlight the high sensitivity and specificity of HIFI-PROF in identifying cancer cases while maintaining a low rate of false-positive results. The use of HIFI-PROF offers a cost-effective MCED test with excellent performance. Such advancements will contribute to improve strategies for multi-cancer early detection, leading to more effective clinical interventions and better outcomes.
Significant results from a major multi-year, multi-cancer follow-up study with an enrollment of over 19,000 individuals.
Authors: Yu Chris Chang , Du Xuedong , Lin Yue , Tang Xing
Published: June 2024

10539

Background: Multi-cancer screening has become a major approach for early stage cancer screening and prevention. However, there has been very few reported multi-year, multi-cancer follow-up studies to validate the effectiveness of multi-cancer screening. We report a number of significant, major findings from what we believe the first large scale, multi-year, multi-cancer follow-up study. Methods: In this study, cancer differentiation analysis (CDA) technology, a bio-physics based detection platform, has been used to screen over 200,000 individuals in a general population. Based on the CDA test values, individuals have been classified into high risk, medium risk and low risk (for cancer) groups. Up to January 31, 2024, a total of 19,141 individuals have been enrolled, with 1,122 in high risk, 15,784 in medium risk, and 2,235 in low risk group. In this follow-up study, enrolled individuals were initially contacted within 6 months (high risk individuals were contacted within 15 days after the test report became available) and subsequently on an annual basis, and their health conditions were recorded. Results: Up to January 31, 2024, 256 individuals have been confirmed with cancer, 1,607 confirmed with pre-cancer diseases and benign tumors, and finally, 1,378 confirmed with diseases. When enrollment is normalized (number of individuals enrolled into each group is equal), for confirmed cancer group, 91.4% is in high risk group, 7.5% in medium risk group and only 1.1% in low risk group. The above result is very significant, indicating that multi-cancer screening using CDA technology is very effective. As shown, there are 23 types of cancer (Table). There are close to 30 types of pre-cancer diseases and benign tumors confirmed. Above results showed that CDA technology is indeed very effective in screening out multiple cancer types (including some cancer types which do not yet have other effective IVD tests such as thyroid cancer and esophageal cancer). The results also show that this approach is very helpful for cancer prevention as it screened out large number of pre-cancer diseases and benign tumor types. Conclusions: A large scale, multi-year, multi-cancer follow-up study has been carried out. Results showed that CDA technology is effective for multi-cancer screening in a general population.[Table: see text]
Estimating risk for pancreatic cancer among 9.4 million veterans in care.
Authors: Wang Louise , Rahimi Larki Navid , Skanderson Melissa , Tate Janet , Hauser Ronald G , Brandt Cynthia , Yang Yu-Xiao , Justice Amy C.
Published: June 2024

10544

Background: Screening for pancreatic ductal adenocarcinoma (PDAC) has focused on individuals with a hereditary component, accounting for only 10% of PDAC events. Using the electronic health record, we developed a PDAC risk prediction model in a general population in the Veterans Health Administration (VA), the largest integrated health system in the US. Methods: We included all individuals from 2002- 2021 with ≥1 inpatient or outpatient VA encounter and recorded race, starting follow-up 1.5 years after first VA encounter. We excluded those who developed PDAC before start of follow-up. We used the multivariable Cox proportional hazards model in the derivation dataset (random 70% of cohort) to estimate the coefficients associated with each predictor for our outcome, time to PDAC (3 and 10 years), censoring at loss to follow-up or 12/31/2021. Candidate predictors included age, gender, race/ethnicity, sex, BMI, smoking status, alcohol use (alcohol use/related disorders and AUDIT-C), diabetes, pancreatitis, Hepatitis C, HIV, liver disease, cholecystectomy, pancreatic cysts, Charlson comorbidity index and common laboratory values. Selection of predictors was based on clinical reasoning, extent of missing values and model fit (Akaike Information Criterion and Harrell’s c–statistic). We evaluated model discrimination using c – statistic and model calibration comparing observed Kaplan – Meier estimated incidence vs. predicted risk score. Results: Among 9.4 million individuals, we observed 19,839 cases of PDAC within 10 years (6,022 cases within 3 years). Median baseline age was 58.5 years, 75.0% were White, and 16.3% were Black. Final predictors included age, gender, smoking, alcohol use (alcohol use/related disorders and AUDIT-C), BMI, diabetes, pancreatitis, pancreatic cyst, and history of cancer (Table, c-statistic in the derivation cohort 3 years: 0.79; 10 years: 0.77). Ten-year risk ranged maximally from 0-5.5%. Preliminary studies suggest labs do not clinically improve model performance. Conclusions: We developed a novel prediction model using available clinical data in a general population that identifies PDAC with high accuracy. Future work will try to identify additional predictors to improve the range of risk predicted. We will validate our findings in the testing set and in external cohorts. [Table: see text]