bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the epidemiology and perceived efficacy of cannabis use in patients with chronic musculoskeletal pain
Authors: Leroux Timothy , Ajrawat Prabjit , Sundararajan Kala , Maldonado-Rodriguez Naomi , Ravi Bheeshma , Gandhi Rajiv , Rampersaud Raja , Veillette Christian , Mahomed Nizar , Clarke Hance
Published: July 2024

Background

The belief that cannabis has analgesic and anti-inflammatory properties continues to attract patients with chronic musculoskeletal (MSK) pain towards its use. However, the role that cannabis will play in the management of chronic MSK pain remains to be determined. This study examined 1) the rate, patterns of use, and self-reported efficacy of cannabis use among patients with chronic MSK pain and 2) the interest and potential barriers to cannabis use among patients with chronic MSK pain not currently using cannabis.

Methods

Self-reported cannabis use and perceived efficacy were prospectively collected from chronic MSK pain patients presenting to the Orthopaedic Clinic at the University Health Network, Toronto, Canada. The primary dependent variable was current or past use of cannabis to manage chronic MSK pain; bivariate and multivariable logistic regression were used to identify patient characteristics independently associated with this outcome. Secondary outcomes were summarized descriptively, including self-perceived efficacy among cannabis users, and interest as well as barriers to cannabis use among cannabis non-users.

Results

The sample included 629 patients presenting with chronic MSK pain (mean age: 56±15.7 years; 56% female). Overall, 144 (23%) reported past or present cannabis use to manage their MSK pain, with 63.7% perceiving cannabis as very or somewhat effective and 26.6% considering it as slightly effective. The strongest predictor of cannabis use in this study population was a history of recreational cannabis use (OR 12.7, p<0.001). Among cannabis non-users (N=489), 65% expressed interest in using cannabis to manage their chronic MSK pain, but common barriers to use included lack of knowledge regarding access, use and evidence, and stigma.

Conclusions

One in five patients presenting to an orthopaedic surgeon with chronic MSK pain are using or have used cannabis with the specific intent to manage their pain, and most report it to be effective. Among non-users, two-thirds reported an interest in using cannabis to manage their MSK pain, but common barriers to use existed. Future double-blind placebo-controlled trials are required to understand if this reported efficacy is accurate, and what role, if any, cannabis may play in the management of chronic MSK pain.
A privacy-preserving image retrieval scheme with access control based on searchable encryption in media cloud
Authors: Tian Miao , Zhang Yushu , Zhang Yongming , Xiao Xiangli , Wen Wenying
Published: July 2024

With the popularity of the media cloud computing industry, individuals and organizations outsource image computation and storage to the media cloud server to reduce the storage burden. Media images usually contain a large amount of private information. To prevent disclosure of privacy of the image owners, media images are encrypted before uploading to the server. However, this operation will greatly limit the utilization of the image for the user, such as content-based image retrieval. We propose an efficient similarity query algorithm with access control based on Bkd-tree in this paper, in which a searchable encryption scheme is designed for similarity image retrieval, and the encrypted image is used to extract image features by a pre-trained CNN model. The Bkd-tree is utilized to generate an index tree for the image features to speed up retrieval and make it faster than linear indexing. Finally, the security performances of the proposed scheme is analyzed and the performance of this scheme is evaluated by experiments. The results show that the security of the image content and image features can be ensured, and it has a shorter retrieval time and higher retrieval efficiency.
Characterization of the fungal genus Sphaerellopsis associated with rust fungi: species diversity, host-specificity, biogeography, and in-vitro mycoparasitic events of S. macroconidialis on the southern corn rust, Puccinia polysora
Authors: Gómez-Zapata Paula Andrea , Díaz-Valderrama Jorge Ronny , Fatemi Samira , Ruiz-Castro Cristhian Orlando , Aime M. Catherine
Published: July 2024

Sphaerellopsis species are putative hyperparasites of rust fungi and may be promising biological control agents (BCA) of rust diseases. However, few detailed studies limit potential BCA development in Sphaerellopsis. Here, we explored the biogeography, host-specificity, and species diversity of Sphaerellopsis and examined the early infection stage of one species, S. macroconidialis, to infer its trophic status. We randomly screened 5,621 rust specimens spanning 99 genera at the Arthur Fungarium for the presence of Sphaerellopsis. We identified 199 rust specimens infected with Sphaerellopsis species on which we conducted morphological and multi-locus phylogenetic analyses. Five Sphaerellopsis species were recovered, infecting a total of 122 rust species in 18 genera from 34 countries. Sphaerellopsis melampsorinearum sp. nov. is described as a new species based on molecular phylogenetic data and morphological features of the sexual and asexual morphs. Sphaerellopsis paraphysata was the most commonly encountered species, found on 77 rust specimens, followed by Sphaerellopsis macroconidialis on 56 and S. melampsorinearum on 55 examined specimens. The type species, Sphaerellopsis filum, was found on 12 rust specimens and Sphaerellopsis hakeae on a single specimen. We also recovered and documented for the first time, the sexual morph of S. macroconidialis, from a specimen collected in Brazil. Our data indicate that Sphaerellopsis species are not host specific and furthermore that most species are cosmopolitan in distribution. However, S. paraphysata is more abundant in the tropics, and S. hakeae may be restricted to Australia. Finally, we confirm the mycoparasitic strategy of S. macroconidialis through in-vitro interaction tests with the urediniospores of Puccinia polysora. Shortly after germination, hyphae of S. macroconidialis began growing along the germ tubes of P. polysora and coiling around them. After 12 days of co-cultivation, turgor loss was evident in the germ tubes of P. polysora, and appressorium-like structures had formed on urediniospores. The interaction studies indicate that Sphaerellopsis species may be more effective as a BCA during the initial stages of rust establishment.
The effect of transferring a low-quality embryo along with a high-quality embryo on the pregnancy outcome
Authors: Huang Xianju , Lu Xinle , Jiang Xue , Chao Ludan , Wang Xiao
Published: July 2024

Background

Previous evidence suggests that low-quality embryos may send negative signals to the endometrium and affect the receptivity of the endometrium. This study aimed to evaluate the influence of transferring an additional low-quality embryo with a high-quality embryo on the pregnancy outcome.

Methods

A total of 1506 fresh embryo transfer cycles between January 2018 and June 2020 were included. The patients were separated into two groups: a single embryo transfer group (SET, patients receiving a single high-quality embryo) and a double embryo transfer group (DET, patients receiving a high-quality embryo and a low-quality embryo). Main outcome measures including multiple pregnancy rate and live birth rate were discussed.

Overall, in the primary analysis, patients who receive an additional low-quality embryo improved the live birth by 8.7% and multiple pregnancy rate by 10.0%. In women aged less than 35 years, compared with SET, DET increased the birth rate by 6.0% but resulted in a 13.5% increase in multiples. Women of 35 years above, adding a low-quality embryo increased the live birth rate by only 2.2% but increased multiples by 14.7%. In patients with one cycle of ET, the same results were obtained. In patients with multiple cycles of ET and adding a low-quality embryo, the live birth rate was similar to SET but with a 14.7% increase in multiples.

Conclusions

Compared to DET, we prefer to transfer a high-quality embryo. Nevertheless, in women 35 years or older or in patients with multiple cycles of embryo transfer, adding a low-quality embryo did not significantly improve live birth but increased the multiple rate.
Revealing complex subsurface dynamics with continuous seismic monitoring: Observations using distributed acoustic sensing and surface orbital vibrators during hydraulic fracturing
Authors: Correa Julia , Glubokovskikh Stanislav , Nayak Avinash , Luo Linqing , Wood Todd , Zhu Xiaoyu , Ajo-Franklin Jonathan , Freifeld Barry
Published: July 2024

Understanding hydraulic fracturing is crucial to improving the stimulation of unconventional reservoirs and increasing fluid production. This study develops a novel seismic monitoring technology using distributed acoustic sensing (DAS) and surface orbital vibrators (SOV) to capture fracture seismic response and mechanical properties at high temporal intervals. We analyze continuous time-lapse vertical seismic profiling (VSP) data acquired every hour during the first nine days of treatment of an unconventional reservoir in the Austin Chalk/Eagle Field Laboratory. The VSP data contain clear seismic signals scattered from the activated fractures. The spatiotemporal changes of the fracture reflectivity revealed by the SOV/DAS data correlate well with the observations of fracture locations inferred from low-frequency DAS data. These results capture the fracture opening and closure processes, as well as highlight potential prestage activations of the fractures due to hydraulic connectivity with preexisting fracture systems. Therefore, analysis of the presented data set provides a unique opportunity to understand fracture initiation and subsequent evolution, not only in the context of unconventional resources but also in enhanced geothermal systems.
Prevalence of recreational and medical cannabis products in Veterans and their interactions with cancer directed pharmacological treatment.
Authors: Todorova Tsvetelina V , John Elizabeth , Sareen Srishti , Tandra Vaishnavi , Davis Jessica Daune Rich , DiLoreto Nicholas A , Weir Alva Bowen
Published: July 2024

3089

Background: There is proliferation of literature about the medical uses of cannabis products in patients with malignancies. However, research is lacking as to how cannabis use is affecting the efficacy and toxicity of anti-neoplastic regimens It is known that cannabis is metabolized by the cytochrome p450 pathway, the same as many anti-neoplastic agents and thus there are concerns for potential interactions. Methods: We report an observational study to identify cannabis users in veterans receiving anti-neoplastic therapy in the Memphis VA health system, and to then analyzed for potential interactions between cannabis product and the antineoplastic agent/s they were receiving. Data was collected via voluntary surveys. We then reviewed their charts, recorded the anti- neoplastic medications they were receiving, and evaluated for potential interactions with cannabis, based on a literature review of potential interactions. Results: In this study, 132 veterans agreed to participate. 50 of them acknowledged recent use of cannabis products within the last 90 days. Thus, the prevalence of cannabis use amongst those who participated is 37.87%. Demographically, 10% of the cannabis users were female, and 90% were male, with the majority aged 60-65 (range 46-85). Predominantly, patients inhaled cannabis once daily (38%) as opposed to using a different formulation. The patients who admitted cannabis use were primarily on chemotherapy (42%), while 38% were on immunotherapy, 24% were on targeted therapy and 20% were on endocrine therapy. Some were on multiple drugs. Based on this data and a literature search for interactions, we found that a significant number of the patients in our Veteran’s oncology clinic have a potential increase in toxicity or decreased efficacy from their ant-neoplastic therapy due to CYP interactions with cannabis use. Conclusions: In this exploratory study, we discovered a notable prevalence of patients concurrently using cannabis products while on anti-neoplastic treatment. Given that many anti-neoplastic agents undergo metabolism via the CYP450 pathway, our data suggest that a moderate number of patients in our clinic risk less than optimal outcomes due to concurrent cannabis and anti-neoplastic therapy. To delve deeper, we intend to conduct a follow-up study, focusing on specific adverse effects, hospitalizations, and the subsequent need for 2nd and 3rd line treatments in patients using cannabis. A much larger multi-institutional study should be considered to provide statistically relevant data on true outcomes. [Table: see text]
A phase 2 study of de-escalation in resectable, locally advanced cutaneous squamous cell carcinoma (cSCC) with the use of neoadjuvant pembrolizumab: De-Squamate.
Authors: Ladwa Rahul , Lee Jenny HJ , Porceddu Sandro V , McGrath Margaret Louise , Cooper Caroline , Liu Howard , Gupta Ruta , Cuscaden Claire , Nottage Michelle K. , Clark Jonathan , Le Dieu , Pauley Marketa , Gonzalez-Cruz Jazmina , Frazer Ian , Hughes Brett Gordon Maxwell , Panizza Benedict J
Published: July 2024

9514

Background: Neoadjuvant anti-Programmed Death therapy has shown a 64% complete or major pathological response rate in patients (pts) with resected stage II-IV(M0) cSCC. The De-Squamate study (NCT05025813) evaluated the feasibility of a risk adapted surgical de-escalation approach guided by clinical, radiological and pathological response in resectable cSCC pts of all sites receiving neoadjuvant pembrolizumab. Methods: This multi-centre, open-labelled, non-randomised, single-arm phase 2 study evaluated the response of neoadjuvant Pembrolizumab for 4 cycles administered IV 200mg Q3W in immunocompetent pts with Stage II-IV (M0) resectable cSCC. Pts underwent CT/MRI and 18F-FDG-PET imaging at baseline and following completion of neoadjuvant pembrolizumab. In those with a complete metabolic response, mapping biopsies of target site(s) were performed and if negative for residual SCC (clinical complete response [CCR]), surgery and post operative radiation therapy (PORT) were omitted. Patients with clinical or radiological residual disease/ positive mapping biopsy underwent surgical resection. PORT was de-escalated if there was a pathological complete response (PCR - no residual tumour cells) or major pathological response (MPR - less than or equal to 10% viable tumour cells). Pts proceeded to 13 cycles of maintenance Pembrolizumab. The primary endpoint was the combined rate of PCR, MPR and CCR following neoadjuvant Pembrolizumab and secondary endpoint includes treatment de-escalation and safety. Results: All 27 patients were enrolled and received a minimum of 2 cycles of neoadjuvant Pembrolizumab. The primary endpoint was observed in 17 patients (63%, 95% CI: 42-80), comprised of PCR (15%), MPR (0%) and CCR (48%). De-escalation of both surgery and PORT was achieved in 48% and a further 15% avoided PORT alone. With a minimum follow up of 6 months, no pts with PCR/MPR/CCR recurred. Investigator assessed treatment-related adverse events ≥ grade 3 was seen in 2 patients (7%). Conclusions: Pembrolizumab led to a high rate of PCR and CCR in resectable cSCC. The de-squamate study design effectively selected pts for surgical and PORT de-escalation and demonstrated a sustained response in this cohort. Clinical trial information: NCT05025813 .
Prediction of CCL2 in breast cancer based on enhanced MRI radiomics model with integrated bioinformatics analysis and machine learning.
Authors: Fu Chen , Chen Qiuchen
Published: July 2024

e12509

Background: Breast cancer is the most common malignant tumor in women. According to the 2023 Cancer Statistics Report, breast cancer has surpassed lung cancer to become the most common malignant tumor. Its incidence and mortality both rank first among female malignant tumors. This study proposes non-invasive prediction of CCL2 mRNA expression in breast cancer tissue through enhanced MRI radiomics, while integrating bioinformatics analysis to explore the underlying molecular mechanisms and their association with the immune microenvironment. Methods: Excluding criteria were applied to select primary solid tumor samples with RNA-seq data (n = 840) from the TCGA-BRCA database. Enhanced MRI imaging data (n = 98) intersecting with the TCGA-BRCA data were obtained from TCIA-BRCA. The imaging data were randomly divided into training (n = 70) and testing sets (n = 28) in a 7:3 ratio. A feature subset was selected, and a model was constructed using the support vector machine (SVM) algorithm in the training set. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and the Hosmer-Lemeshow goodness-of-fit test. The calibration of the radiomics prediction model was assessed using the Brier score, and the clinical utility of the radiomics prediction model was demonstrated by drawing decision curves (DCA). External validation of the model was performed using a validation set. The radiomics score (RS) was calculated using the LR radiomics model and categorized as a binary variable (Low/High RS). Subsequently, KEGG pathway, immune-related genes, and gene mutation analysis were conducted based on the CCL2 high and low expression levels. Results: A total of 1810 radiomic features were obtained with ICC values ≥ 0.75. Subsequently, the mRMR (Maximum relevance, minimum redundancy) method, and the optimal 7 feature subsets were further identified using the RFE (Recursive feature elimination) algorithm. The SVM model demonstrated favorable predictive performance, with an AUC value of 0.822 for the training set and 0.779 for the validation set, as indicated by the ROC curve. Calibration curve and Hosmer-Lemeshow goodness-of-fit test revealed good consistency between the radiomic predictive model for the probability of high gene expression and the actual values (P > 0.05). Additionally, the decision curve analysis (DCA) demonstrated high clinical utility of the model. The TNF-α signaling pathway was found to influence the occurrence and development of breast cancer. Furthermore, the degree of Plasma Cell infiltration was observed to be highest in breast cancer. Conclusions: The CCL2 model constructed using a combination of machine learning and radiomic features, can non-invasively predict the prognosis of breast cancer treatment and exhibits good generalizability.
Efficacy of a combined diet and exercise intervention in patients with breast cancer undergoing chemotherapy: A meta-analysis of randomized controlled trials.
Authors: Roca Mora Maria Meritxell , Marin Cunha Luisa , Kozhokar Mikhaylovskaya Angelina , Afzal Farhan , Godoi Amanda
Published: July 2024

e12517

Background: Breast cancer treatment presents challenging side effects that may compromise patients’ health and quality of life (QoL). While exercise programmes have been shown to improve survival, the impact of combined exercise and dietary interventions compared to usual practices alongside chemotherapy remains controversial. Methods: PubMed, Embase, Cochrane Central, and ClinicalTrials.gov were systematically searched up to October 2023. We included randomized controlled trials (RCTs) involving adult breast cancer patients undergoing chemotherapy and comparing combined diet and exercise interventions with usual care. Outcomes of interest included weight change, relative dose intensity (RDI), and Functional Assessment of Cancer Therapy-General scale (FACT-G) score for QoL. Statistical analysis was performed using Review Manager 5.4.1 and RStudio version 4.1.2. The protocol was registered on PROSPERO (ID: CRD42023463543). Results: Seven RCTs with 960 patients undergoing breast cancer therapy were included, of whom 506 (53%) were assigned to combined exercise and dietary interventions. Participants had a mean BMI of 26.6 kg/m2, and approximately 52% were postmenopausal. Combined exercise and dietary interventions resulted in significant reductions in weight loss (MD -1.06 kg, 95% CI -1.68 to -0.44; p<0.01), BMI (MD -0.44; 95% CI -1.76 to -0.13; p<0.01), body fat (MD -2.12%; 95% CI -3.99 to -0.26; p=0.03), and FACT-G (MD -3.40; 95% CI -6.25 to -0.55; p=0.02) compared to usual care. No significant differences were observed in waist circumference (p=0.05), RDI (p=0.23), or fatigue levels (p=0.98) between groups. Conclusions: In this meta-analysis of randomized trials, combined exercise and dietary interventions improved weight management in breast cancer patients undergoing chemotherapy but did not significantly impact chemotherapy completion, fatigue levels, and worsened FACT-G score (QoL). Findings can help to further holistic cancer care, taking into account both physical and psychosocial dimensions of patient health.
Clinical outcomes and prognostic factors in epithelial-myoepithelial carcinoma (EMC) of the breast.
Authors: Joshi Utsav , Budhathoki Pravash , Gaire Suman , Niu Chengu , Neupane Niraj , Agrawal Vishakha , Soliman Hatem Hussein
Published: July 2024

e12529

Background: EMC is a biphasic neoplasm of the breast and comprises of malignant components derived from both luminal epithelium and myoepithelium. Most of the published data on EMC consists of individual case reports, and hence survival outcomes and prognosis are not clearly defined to guide evidence‐based management. We aimed to evaluate the clinical characteristics, survival outcomes, and prognostic factors in patients with EMC. Methods: All women with a histologic diagnosis of EMC irrespective of age and stage at diagnosis till 2018 in the National Cancer Database (NCDB) were included (N=111). Overall survival (OS) was assessed utilizing the Kaplan–Meier method and compared among groups using the log-rank test. Results: The median age at diagnosis was 67 years, and 101 (88.6%) were greater than 50 years of age. Most women were white (84.7%), non-Hispanic (91.9%), had a Charleston-Deyo score of 0-1 (95.5%), and treated at an academic or comprehensive community cancer programs (70.2%). Ten percent of patients were ER+/Her2-, 29.7% were ER-/Her2-, 0.9% were Her2+, 5.4% were ER+/Her2 unknown, 24% were ER-/Her2 unknown, and 29.7% had no data on ER status. Almost one-third of the women had poorly differentiated or undifferentiated tumors. Of the patients with available data, 46.7% had tumor ≤2 cm and more than 97% had no lymph node involvement or metastases. Most underwent surgical resection- radical mastectomy (16.2%), total mastectomy (18.9%), and partial mastectomy (56.8%). Chemotherapy and radiation were utilized in 35.2% and 40.6% of the women, respectively. At a median follow up of 67.6 months, the 3-year and 5-year OS was 81.6% and 74.3% respectively. The 5-year OS was 82.7%, 76.5%, and 50% for tumor ≤2 cm, 2-5 cm, and >5 cm respectively (p=0.009). Details on 5-year OS based on chemotherapy, radiation, and tumor size are shown in the table below. Among women who underwent lumpectomy (N=35), the 5-year OS for those who received adjuvant radiation vs surgery alone was 81.9% vs 76% (p=0.4). Conclusions: EMC demonstrates distinctive clinicopathologic features and receptor status. Administration of chemotherapy or radiation was associated with improved OS in tumors >5 cm, although small sample size and lack of recurrence data may limit this conclusion. Further studies using larger cohorts are needed to demonstrate objective efficacy of systemic treatment in lymph node positive and metastatic EMC. [Table: see text]
Risk factors for positive margin in breast conservation surgery for localized breast cancer.
Authors: Ferrick James P , Zubair Hina , Salvi Sumeet , Davis Elaine A , Welch Christine A , Kamran Amir Shahzad
Published: July 2024

e12539

Background: Breast cancer is an evolving global concern due to its increasingly high morbidity and mortality rates. This is, in part, due to health care disparities in breast cancer patients that have been a problem for screening, diagnosis, and treatment. Breast-conservation surgery (BCS) is defined as the removal of breast tumor tissue surrounded by a margin of normal tissue and includes lumpectomy, partial mastectomy, wide excision, and segmental mastectomy. Negative margins post-BCS are necessary to avoid any breast cancer recurrence. A negative margin is defined as no gross or microscopic disease, also known as no tumor on ink. Positive margins are associated with patients who may have to undergo re-excisions with larger margins or total mastectomy, exposing patients to greater morbidity and delaying the start of adjuvant therapy. Methods: This was a retrospective cohort study designed to examine factors associated with positive margins (PM) in breast cancer patients undergoing breast-conserving surgery. The Charleston Area Medical Center cancer registry was queried from 2009-2022 for females diagnosed with invasive breast cancer who had surgery for localized disease (TxN0M0), excluding those with previous malignancies. Data were analyzed with SAS 9.4 using student’s t-test for continuous variables, Chi-square or Fisher’s exact for categorical variables, and multivariate analysis to identify factors predictive of positive margins. Results: In total, 1133 female patients with mean age of 64±11 met inclusion criteria. The positive margin group (PMG) made up 10.2% of the population while the negative margin group (NMG) was 89.8%. The PMG had significantly (p < .0001) larger tumors than the NMG, 19.7±12 and 13.8±9, respectively. Multifocal tumors made up 18% of the PMG compared to 4.4% of the NMG (p < .0001). Invasive lobular carcinoma made up 20% of the PMG compared to 7.2% of the NMG (p = .003). Recurrence was significantly (p = .030) higher in the PMG compared to the NMG, 7.4% and 3.2%, respectively; however, 5-year survival showed no difference. Regression modeling showed that multifocal tumors were 4.4 times (95% CI: 2.4-8; p < .0001) more likely to be associated with PM, lobular carcinoma was 2.8 times (95% CI: 1.6-4.8; p = .0003) more likely to be associated with PM, and stage II patients were 2.4 times (95% CI: 1.5-3.7; p = .0002) more likely to have PM. Conclusions: Univariately, tumor size, multifocality, lobular carcinoma, stage II, and local/distant recurrence were all associated with positive margins. This finding was re-demonstrated with respect to multifocality, lobular carcinoma, and stage II following multivariate analysis. The results of this study may help to guide surgeons and oncologists in the management of localized, invasive breast cancer, especially in emphasizing the importance of timely follow-up in patients at higher risk and in the education of patients regarding their care.
Intraoperative ultrasound guided wire (IOUS-wire) localization biopsy with frozen section versus preoperative fine needle aspiration cytology (FNAC) for the evaluation of clinically positive nodes in patients with early breast cancer in China real-world clinical practice.
Authors: Song Xue , Chen Qianjun , He Jiafa , Xu Rui , Tan Shijun , Dai Yan , Ye Lingling , Lin Xiaojie
Published: July 2024

e12600

Background: Appropriate biopsy procedure for clinically positive (suspicious) lymph nodes (LN) plays a key role in accurate axillary staging of early breast cancer. Fine needle aspiration (FNA) is a recommended method for clinically suspicious nodes in the National Comprehensive Cancer Network (NCCN) guidelines. However, the false negative rate (FNR) of FNA remains too high. Therefore, it is valuable to explore an alternative and appropriate procedure in clinical practice. We conducted a retrospective review to compare the feasibility and diagnostic efficiency of using a novel procedure, the intraoperative ultrasound guided wire (IOUS-wire) localization biopsy with frozen section, to FNA for assessment of clinically positive nodes in patients with early breast cancer. Methods: Data on consecutive primary breast cancer patients with documented axillary ultrasound results who had clinically positive lymph nodes (cN1) between January 2015 and September 2023 either utilization of IOUS-wire localization or ultrasonography-guided fine-needle aspiration cytology (US-FNAC) for clinically positive lymph nodes were retrospectively analyzed. Sentinel lymph node biopsy (SLNB) was performed in patients with negative histopathological or cytological results. The false negative rate (FNR) of histopathology between two groups was calculated. Results: Eligible patients (n=198) referred to axillary biopsy by IOUS-wire localization biopsy(n=100) and US-FNAC(n=98) in this study. The FNR of clinically positive lymph nodes biopsy was 12.8 percent in the IOUS-wire localization group and 87.5 percent in the US-FNAC group.IOUS-wire failed in 5 patients. Among the remaining 32 successful identifications, 26 were IOUS-wire-node positive by intraoperative frozen section. 42 patients with additional lymph node metastases were found in FNAC-LN-negative patients by SLNB. The accuracy rate was respectively 95% and 57.1%. No significant difference was observed in complications and median number of SLNs harvested (5.3 versus 5.5; P=0.631) between the groups. Sufficient tissue samples can be obtained for intraoperative frozen pathology so the FNR is potentially reduced. In addition, the interval of waiting time for pathological results is reduced. Conclusions: Intraoperative US-guided wire localization biopsy is a feasible and alternative procedure compared to preoperative FNA for clinically node-positive patients with early breast cancer. This novel method is suitable for China's national conditions and should be further pursued as a potential biopsy method for evaluation of axillary node status in clinical practice.
Current trends in lung cancer brain metastases trials.
Authors: Petrosyan Edgar , Fares Jawad , Fernandez Luis G. , Oyon Daniel E. , Gibson William S. , Sonabend Adam M. , Lesniak Maciej S.
Published: July 2024

e14006

Background: Brain metastases are the predominant central nervous system malignancy, primarily originating from lung cancer. In the era of precision medicine, enhanced control of extracranial disease is increasing the incidence of brain metastases, underscoring their status as a growing unmet need in modern Neurooncology. Methods: On December 12, 2023, we searched ClinicalTrials.gov for interventional and therapeutic clinical trials focusing on lung cancer brain metastases (LCBM). We gathered information on trial characteristics, including phase, study design, primary and secondary endpoints, status, enrollment criteria, size, duration, and results. Subsequently, the collected data was subjected to systematic analysis. Results: Among 198 identified trials, the majority were in early phases: 12% in phase I, 6% in phase I/II, and 60% in phase II. Only 27% of trials in phase II & II/III were randomized, with 92% lacking blinding. Trials were concentrated in North America (36%) and Asia/Africa/Australia (33%), predominantly targeting non-small cell lung cancer (NSCLC) (82%). Patients with leptomeningeal metastases were included in only about 10.5% of the trials. Out of 44 completed trials, only 21 resulted in published original articles. Termination occurred in 38 trials, primarily due to insufficient participant enrollment. Tyrosine kinase inhibitors emerged as promising treatments for brain parenchymal and leptomeningeal NSCLC metastases. Conclusions: This study highlights critical deficiencies in LCBM trials, ranging from inadequate trial numbers and recruitment difficulties to the overwhelming focus on NSCLC trials, insufficient randomization and blinding, and a marked scarcity of trials involving patients with leptomeningeal metastases. Addressing these issues is pivotal for advancing the understanding and treatment of LCBM.
HLA class-I antigen presentation machinery (APM) alterations mediate immune evasion in lung cancer brain metastases.
Authors: Vilariño Noelia , Lopez De Rodas Miguel , Ranjan Kishu , Costantini Adrien , Villalba Maria , Lu Benjamin Y. , Kravitz Caro , Nadal Ernest , Goldberg Sarah B. , Nguyen Don , Schalper Kurt A.
Published: July 2024

e14014

Background: Although ~30% of patients with lung cancer brain metastasis (LBM) achieve intracranial response with immune checkpoint inhibitors (ICI), most have primary resistance, and those who initially respond develop rapid disease progression. The biological factors contributing to this unfavorable clinical scenario are poorly understood and could include distinct immunologic properties of tumors colonizing the brain. Using annotated tumor/patient cohorts, spatially resolved protein analysis, and in vitro models, we investigated the role of HLA class-I APM defects and interferon (IFN)-γ pathway in LBM. Methods: Using multiplex quantitative immunofluorescence, we measured the levels and spatial distribution of HLA class-I APM markers (β2M, tapasin, calreticulin, ERp57, TAP1, and TAP2), IFN-γ signaling (pSTAT1 and IRF-1), and tumor-infiltrating lymphocytes (TILs) (CD8, CD4, and FOXP3) in 56 LBM, 41 primary lung tumors (PLT), and 10 lung-extracranial metastases (ECM) represented in tissue microarrays. A subset of paired LBM/PLT samples from the same patients were also included (n=8). The spatial analysis of the markers was conducted using fluorescence co-localization and single-cell segmentation strategies. Associations between the markers, clinicopathological characteristics, and survival were studied. Protein expression of β2M and IFN-γ-sensitive markers (total STAT1, pSTAT1, IRF1, and PD-L1) before and after treatment with human recombinant IFN-γ was assessed using Western blot in cultured primary lung H2030 adenocarcinoma cells and their in vivo selected brain metastatic counterpart H2030-BrM3. Results: LBM showed significantly lower β2M, TAP2, and tapasin protein levels than PLT. However, LBM also showed higher expression of pSTAT1 and comparable levels of IRF-1 relative to PLT. Similar results were seen in paired LBM/PLT samples, but not in ECM samples. Tumors with low β2M showed reduced CD8+, CD4+, and FOXP3+ TILs. In LBM no significant association between β2M and IFN-γ pathway markers or major clinicopathologic and molecular patient/tumor features were found. LBM samples from patients progressing after radiotherapy and/or chemotherapy showed significantly lower β2M levels. Reduced β2M expression was associated with shorter overall survival in PLT but not in LBM. The brain metastatic H2030-BrM3 cell line showed lower β2M expression both at baseline and after IFN-γ treatment compared with their parental H2030 counterpart. Conclusions: HLA class-I APM downregulation is a prominent feature of LBM, is independent of local adaptive/inducible IFN-γ stimulation, and is associated with unfavorable clinical features. These findings support that HLA class-I APM deficiency plays a major role in immune evasion and immunotherapy resistance in patients with LBM.
Deep learning for 4D modeling of glioblastoma multiforme with tumor treating fields (TTFields) therapy.
Authors: Guerrero Ramirez Andres Felipe , Tang Cynthia Crystal , Kong Xiao-Tang , Bota Daniela Annenelie , Chang Peter D.
Published: July 2024

e14032

Background: Prediction of future tumor growth and recurrence are critical in the management of patients with glioblastoma multiforme (GBM). This study develops a deep learning method for estimating future areas of GBM spread across multiple timepoints using MRI in patients receiving tumor treating fields (TTFields) therapy. Methods: A single institutional database was queried to identify adult patients with histologically confirmed newly diagnosed and/or recurrent GBM undergoing TTFields therapy. For newly diagnosed GBM, patients received TTFields with temozolomide after maximal debulking surgery and chemoradiation therapy. For recurrent GBM, patients received TTFields as monotherapy. For each patient, all serial follow-up MRI exams were obtained, including T1 (pre-/post-contrast), T2, and T2/FLAIR sequences. On each exam, all regions of enhancing tumor core (excluding peritumoral edema, necrotic core, or resection cavity) were delineated and aligned across time points using nonlinear deformable registration. For any given pair of serial exams, a convolutional neural network (CNN) was designed to predict future GBM tumor on the follow-up exam given the precursor exam and time interval between the studies. The model is implemented as a 3D encoder-decoder architecture yielding a dense per-voxel prediction of future tumor probability optimized using a binary cross-entropy loss function. Class weights were used to develop high sensitivity and high positive predictive value (PPV) model variants. To generate final logit scores, time information is concatenated to the penultimate feature map as an additional feature channel, allowing the model to calibrate each estimate based on elapsed time between any pair of exams. Upon convergence, a 4D learned representation allows for prediction of spatial distribution of GBM tumor at any future time point. Results: A total of 123 patients (1112 total MR exams) were identified. For any given single patient, a median of 6 follow-up exams (IQR 2.5-12.5) at a median interval follow-up time of 46 days (IQR 15.75-63 days) between exams was observed. Upon five-fold cross-validation, the model demonstrated a 0.44 Dice score overlap between predicted and true areas of future GBM tumor growth. The high sensitivity model yielded a per-voxel sensitivity of 0.91 (IQR 0.77-0.99) and PPV of 0.26 (IQR 0.17 to 0.32), while the high PPV model yielded a per-voxel sensitivity of 0.14 (IQR 0.00 to 0.46) and PPV of 0.75 (IQR 0.56 to 0.94). Upon visual confirmation, model predictions across incremental time values for any given exam yielded expected gradual growth of tumor over time. Conclusions: A deep learning model can accurately predict future areas of GBM tumor growth in patients receiving TTFields therapy, with optimal performance that may be calibrated for high sensitivity or high PPV based on clinical use case.
Schwannomas: Experience from a single center reference in Peru.
Authors: Galecio Viera Jianmartin , Paitan Amaro Victor , Castro Oliden Victor
Published: July 2024

e14043

Background: Schwannomas are nerve sheath tumors that originate in Schwann cells. They are usually solitary and sporadic and manifest on peripheral, spinal or cranial nerves. It is the most common type of benign peripheral nerve tumor in adults. These tumors represent a diagnostic challenge due to their rarity and difficult differential diagnosis. Our objective was to determine the clinical and pathological characteristics, as well as the therapeutic management of patients with Schwannoma admitted to our institution over a period of time. Methods: A retrospective, cross-sectional and descriptive study was carried out on the cases of patients with Schwannoma over 14 years of age, diagnosed at the National Institute of Neoplastic Diseases from 2009 to 2023. Medical records and pathology reports were reviewed. Results: A total of 225 patients were diagnosed with schwannoma on anatomopathology. Median age was 44 years, with a range of 15 to 92 years. 135 (60%) patients were female and 90 (40%) male, with a ratio of 1.5:1. 19 (8.4%) patients had a second cancer before or after the diagnosis of schwannoma. 6 (2.66%) patients were previously diagnosed with neurofibromatosis. According to anatomical origin: 27 (12%) patients had schwanommas of the abdominal region, 36 (16%) of the head and neck, 42 (18.66%) of the spinal cord, 17 (7.55%) of the extremities, 83 ( 36.88%) of the intracranial region and 20 (8.88%) of the thorax. At the intracranial level, 71 patients had location at the cerebellopontine angle, 5 at the orbital level, 2 at the level of the cerebellum and 5 in another location. At the abdominal level, 13 patients had a retroperitoneal location, 8 at the gastric level, 2 at the renal level and 4 in another location. In 130 patients we can obtain the ki67, median score was 2% (1-50%). Regarding treatment, 156 (69.33%) patients underwent surgery, and 42 (18.66%) patients received radiation treatment. During their follow-up, only 5 (2.22%) patients had local recurrence. Conclusions: Schwannomas are rare benign tumors. In many cases, its suspected diagnosis is difficult due to its similarity to other tumors that must be part of the differential diagnosis. Its treatment is surgical, with the objective of complete macroscopic resection. Radiotherapy is a complementary treatment in case of residual disease.
Clinical and molecular mechanisms for predicting the efficacy of immunotherapy for hepatocellular carcinoma based on gut microbiome.
Authors: Zhu Wenwen , Zhang Ningning , Yu Yuexi , Huo Yiming , Lu Wei
Published: July 2024

e16222

Background: Hepatocellular carcinoma (HCC) is an aggressive malignant tumor, ranking as the fifth most common cancer and the third leading cause of cancer-related deaths globally, posing a significant global health issue. Increasing evidence suggests that the gut microbiome and their metabolites play a crucial role in the development and therapeutic processes of cancer. Immune checkpoint inhibitors (ICIs) have recently become a treatment option for unresectable advanced HCC. To further guide the selection of immunotherapy for clinical HCC patients, it is necessary to further elucidate the prediction of immunotherapy efficacy for HCC based on the microbiome. Methods: The study enrolled 26 unresectable advanced HCC patients and collected baseline clinical laboratory data. We administered ICIs therapy to HCC patients every three weeks. After 6 months of treatment, patients were divided the responsive group (R group) and the non-responsive group (NR group) based on imaging evaluation according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Prior to the application of anti-tumor treatment, fecal samples were collected from the patients for 16S rRNA microbiome sequencing analysis. Immunofluorescence was used to detect the expression of PD-L1 in tumor tissue, and immunohistochemistry was used to assess changes in lymphocyte subsets CD3+T cells, CD4+T cells, CD8+T cells and Treg cells, as well as the expression of TNF-α, γ-IFN, and GZMB. Additionally, the peripheral blood lymphocyte subsets CD3+T cells, CD4+T cells and CD8+T cells were analyzed by flow cytometry. Results: In our study, R group showed higher taxa richness and more gene counts than those of NR group. Comparing with NR group, the relative abundance of Firmicutes were significantly increased, whereas Proteobacteria and Bacteroidota were significantly decreased in R group at phylum level (all P < 0.05). Our study showed that R group had high level of lymphocyte subsets CD3+T cells and CD8+T cells and low level of CD4+T cells and Treg cells compared to NR group (all P < 0.05). And the expressions of PD-L1, TNF-α,γ-IFN and GZMB were upregulated in R group(all P < 0.05). Conclusions: These findings suggested that the characteristics of gut-microbial diversity and composition at the early treatment period of ICIs therapy in HCC may have distinct implications on drug efficacy and disease prognosis. ICIs therapy reshaped HCC tumor microenvironment in parallel with regulating the gut microbiome and lymphocyte subsets immunity.
The efficacy and safety study of thymosin α1 combined with PD-1 antibodies as adjuvant therapy in patients with hepatocellular carcinoma with high-risk recurrence factors after radical resection.
Authors: RongHua Zhu , Zhiyong Huang
Published: July 2024

e16226

Background: Anti-PD-1 immunotherapy has revolutionized unresectable hepatocellular carcinoma (HCC) treatment. The efficacy of postoperative adjuvant therapy (PAT) using anti-PD-1 in treating HCC is currently the subject of extensive research. This study explored the efficacy and safety of anti-PD-1 antibodies combined with thymosin alpha-1 (Tα1) for patients with HCC and high-risk recurrent factors (HRRFs) post-hepatectomy. Methods: Data from 273 patients with HCC and HRRFs who underwent hepatectomy at Tongji Hospital (January 2019 to July 2022) were prospectively collected. Patients were nonrandomly divided into Tα1+ anti-PD-1 antibodies (65, 23.8%), anti-PD-1 antibodies (84, 30.8%), and control (no adjuvant therapy, 124, 45.4%) groups based on finances and willingness. After propensity score matching (PSM), recurrence-free survival (RFS) and overall survival (OS) were compared. Cox regression analysis identified the RFS- and OS-related prognostic factors, followed by subgroup analysis. Results: After PSM, 65 patients were matched. The anti-PD-1 antibodies + Tα1 group exhibited longer RFS than the anti-PD-1 antibodies (P = 0.014) and control (P < 0.0001) groups. The anti-PD-1 antibodies group had longer RFS than the control group (P < 0.0001). The anti-PD-1 antibodies + Tα1 (P = 0.00049) and anti-PD-1 antibodies groups (P = 0.0041) demonstrated longer OS than the control group. The 1- and 2-year RFS rates in the Tα1 + anti-PD-1 antibodies, anti-PD-1 antibodies, and control groups were 98.4%, 86.2%, and 49.2% (P < 0.001), and 80.2%, 65.8%, and 24.6% (P < 0.001), respectively. The corresponding 1-, 2-, and 3-year OS rates were 100.0%, 100.0%, and 84.6% (P < 0.001), 98.0%, 91.4%, and 69.0% (P < 0.001), and 91.3%, 86.8%, and 57.4% (P < 0.001), respectively. Multivariable analyses suggested that the Tα1 + anti-PD-1 antibodies treatment improved the RFS and OS more than the non-anti-PD-1 antibodies + Tα1 treatment (hazard ratio (HR): 0.174, 95% confidence intervals (CI): 0.089–0.340, P < 0.001 and HR: 0.240, 95% CI: 0.084–0.683, P = 0.008, respectively). Subgroup analysis demonstrated significant RFS and OS benefits for patients with HCC and vascular invasion treated with Tα1 + anti-PD-1 antibodies. Grade 1 and 2 toxicities included rash/pruritus (21.5%), diarrhea (18.5%), and reactive cutaneous capillary endothelial proliferation (RCCEP)(15.4%). Grade 3 toxicities included RCCEP (1.5%), diarrhea (1.5%), rash/pruritus (0.8%), edema (0.8%), hepatitis (0.8%), nausea/vomiting (0.8%), and hypothyroidism (0.8%). No grade 4/5 toxicities or severe adverse events were detected. Conclusions: Combining anti-PD-1 antibodies with Tα1 as adjuvant therapy is safe, improving postoperative prognosis in patients with HCC and HRRFs after hepatectomy, proving more effective than anti-PD-1 antibodies alone.