bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and biomarker analysis of carboplatin plus taxanes neoadjuvant chemotherapy in triple-negative breast cancer: A prospective multicenter cohort study.
Authors: Chen Xi , Xiu Meng , Kang Hua , Zhang Yan , Yang Hua , Cheng Xueyan , Li Qiao , Li Qing , Wang Jiayu , Lan Bo , Chen Shanshan , Xiao Min , Qian Xiaoyan , Hua Bin , Xu Binghe , Zhang Pin
Published: July 2024

e12619

Background: The efficacy and survival data of carboplatin plus taxane (anthracycline-free) neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) was lack of a large-sample study. The predictive biomarker of efficacy based on cell-free DNA (cfDNA) whole-methylome sequencing (WMS) has not been reported yet. Methods: The prospective multi-center cohort study was conducted in four hospitals of Chinabetween 2016 and 2023. Stage II-III TNBC patients were enrolled to receive NAC of carboplatin (AUC 5) every 3 weeks or carboplatin (AUC 4) every 2 weeks plus taxane(standard dose) for 4-6 cycles. Primary study endpoint were pathological complete response (pCR) and relapse-free survival (RFS). Plasma samples were prospectively collected at baseline (T1) and after NAC(T2). Chromosomal aneuploidy of featured fragments (CAFF),fragment size index (FSI) and methylation density score (MD) of cfDNA were detected with WMS. Results: A total of 267 patients were included in the study. The median age was 49 years, 156 patients (58.4%) were stage III disease. 147 patients (55.1%) received the triweekly NAC. 263 patients underwent breast surgery after NAC and 106 patients (40.3%) achieved pCR. The pCR were similar in biweekly or triweekly groups (39.8% vs 40.7%, P=0.89). The 3-year RFS and overall survival (OS) were 77.9%, 87.6%, respectively. Patients who achieved pCR had a significant better RFS (95.5%) and OS (97.7%) than those non-pCR (76.6%, P<0.001; 81.2%, P<0.001). A total of 66 patients with 120 plasma samples (64 samples at T1, 56 samples at T2) were included in WMS analysis. Patients with CAFF, FSI or MD positive at T1 had a higher tumor burden (stage III or cN2-3, all P values <0.05). The proportion of patients with FSI negative at T2 was significantly higher in pCR group compared to non-pCR(86.2% vs 59.3%, P=0.034). There is a similar tendency in patients with CAFF negative. Patients with MD positive at T1 was significantly associated with poor RFS compared to MD negative (HR = 7.36, 95% CI: 0.93-58.75, Log-rank P=0.028). A linear SVM model based on FSI, CAFF, combining with immune cell (effector memory CD8 T cells, immature B cells) and clinical features was developed to predict pCR, with AUC = 0.90 for training dataset and AUC = 0.86 for testing data. Conclusions: Our large-sample study further confirmed that carboplatin plus taxanes (anthracycline-free) NAC in TNBC is an effective option with clinical applicability. Biomarkers based on cfDNA WMS may offer some predictive and prognostic value which needed to be further investigated.
Plasma microRNA signature as a potential early detection biomarker in breast cancer.
Authors: Simian Marina , Farré Paula Lucia , Duca Rocío , Graña Karen , Magi Gaston , Moro Juana , Scalise Georgina , Guscelli Carla , Casalnuovo Monica Lis , Bayo Sergio , Batagelj Emilio Jose , Zaslavsky Camila , Stigliano Javier , Casimo Carolina , Avila Monica , Benedetti Agustina , Lettieri Graciela , Torlaschi Megan , Diaz Bessone María Inés , De Siervi Adriana
Published: July 2024

e13780

Background: The 5-year survival rate for women with stage I breast cancer (BC) is 99%, falling to 27% if the disease is diagnosed in stage IV. This demonstrates the importance of early detection for the effectiveness of BC treatment. Among the new diagnostic strategies, the use of liquid biopsies is emerging as a promising alternative for early cancer detection and patient follow-up. miRNAs are small non-coding RNA molecules useful as biomarkers, since they can be found in body fluids. Oncoliq’s approach focuses on the relative quantification of a panel of circulating miRNA biomarkers for the early detection of BC using predictive models built with machine learning techniques. Methods: The aim of this work was to identify a highly sensitive miRNA combination based on liquid biopsies together with predictive models, to generate an assay for BC early detection which we named Oncoliq breast. Human plasma samples (n=239) from BC patients and healthy donors (HD) were divided into two cohorts: exploratory (n=66) and validation (n=173). The exploratory cohort was used for the identification of miRNAs using expression microarrays and miRNA-seq. The validation cohort was used for the analytical validation of potential candidates by RT-qPCR. Results: Using ROC curve analysis, 11 miRNAs were identified as potential biomarkers. By RT-qPCR, we validated the expression of the 11 miRNAs. All of them were significantly increased in BC patient samples (n=100) compared to HD (n=73), in accordance with expression microarrays and miRNA-seq results. Using machine learning we established 7 predictive models that combine these miRNAs. After running all the predictive models using logistic regression, the metrics associated with each one were calculated. From these, model 7 showed a sensitivity of 90%, a specificity of 73% and an accuracy of 83%. Conclusions: MiRNAs show satisfactory advantages as biomarkers as they can circulate in body fluids, such as blood and urine. In the presence of diseases such as BC, the level of some specific miRNAs might be altered and this change can be harnessed for detection, diagnosis and prognosis. Here, we generated a panel of 11 miRNAs that showed increased expression in plasma samples from women diagnosed with BC. Oncoliq breast is a promising low cost and highly sensitive novel liquid biopsy test based on circulating miRNAs for BC screening.
The feasibility and preliminary efficacy of a locally developed digital health intervention in improving breast cancer survivor’s quality of life (QOL): Qualitative and quantitative analysis result.
Authors: Bin Ramlee Mohd Hanafi , Abdul Satar Nur Fadhlina
Published: July 2024

e13803

Background: Breast cancer is the most prevalent cancer type amongst females of all ages and the highest reported cancer cases in Malaysia. Breast cancer survivors may have distinctive struggles. Inadequate recovery preparation can have a detrimental effect on the quality of life of breast cancer survivors. Digital health interventions (DHI) can enhance patient rehabilitation. Methods: This is an open-label feasibility study conducted at the University of Malaya Medical Center. The study involved 40 patients diagnosed with stage I-III breast cancer. They were randomly assigned to either the intervention group (12-week program with DHI) or the control group (follow-up at UMMC). Unfortunately, 3 patients withdrew from the intervention group during the study. This resulted in a study size of 17 in the intervention group and 20 in the control group. At the end of the 12-week period, we conducted individual interviews to explore the experiences of DHI users. The primary endpoint of this study was to evaluate the feasibility and acceptability of the smartphone application in enhancing the quality of life for breast cancer survivors. Secondary objectives included estimating the variability of body mass index, health, and physical and psychological status. Results: The study showed the engagement of breast cancer survivors with our Digital Health Intervention (DHI), indicating a 100% retention rate over a 12-week period. This emphasizes the accessibility of DHI, as shown by users logging in at least once within 12 weeks. Quantitative data analysis reveals that the DHI app's engagement rates are 53%, implying that users are logging in at least once a week and over 30% throughout the study period. Farago's study shows a 27-30% user retention rate for medical and health apps within 90 days. (5) Clinical outcome for both control and experimental shown not significant result with p>0.05, however we can appreciate absolute changes in intervention arm BMI. Qualitatively, we are able to code to utility and usability of the DHI apps. Users enjoyed the exercise module, valued admin support, and found the app intuitive. Users were engaged in exercise, diet, and psychology, while disengagement was associated with other social media platforms and personal motivation levels. Conclusions: Study showed a 100% retention rate and a promising 53% engagement rate, showing success in health app engagement. The feasibility study intentionally used a small sample for specific disease and patient demographics. Users reflect on app relevance in exercise, diet, and psychology. In summary, assessing the effectiveness of DHI in providing comprehensive support to cancer survivors requires larger-scale studies.
Remote patient monitoring for early detection of immune checkpoint inhibitor therapy-related pneumonitis in high-risk patients: A pilot-feasibility study.
Authors: Hazim Antonious Ziad , Ruan Gordon , Pritchett Joshua , Anderson Bobby , Leventakos Konstantinos , Egan Ashley
Published: July 2024

e13806

Background: Immune checkpoint inhibitor therapy-related (ICI) pneumonitis poses a significant challenge for patients with cancer. It is associated with increased clinical morbidity and mortality, often resulting in prolonged hospital stays and delays and/or discontinuation of cancer-directed treatment. Early detection and prompt treatment of ICI pneumonitis is critical to improve patient outcomes. Therefore, our institution implemented a remote patient monitoring (RPM) program leveraging in-home, electronic health record-integrated technology and virtual centralized nursing to monitor vital signs and patient symptoms in “high-risk” patients treated with immunotherapy. Methods: Patients receiving immunotherapy deemed to be “high-risk” for ICI pneumonitis seen at Mayo Clinic Rochester, Minnesota were offered enrollment in the RPM program beginning in June 2023. High-risk patients included those with pre-existing lung disease (chronic obstructive pulmonary disease, interstitial lung disease); those with a history of resolved ICI pneumonitis being rechallenged with immunotherapy; and those with grade 1 ICI pneumonitis continuing immunotherapy. Eligible patients who agreed to participate in the program were provided a kit consisting of RPM technology and electronic symptom questionnaires. The kit included an armband for continuous vital sign monitoring, a blood pressure monitor, a scale to measure weight, and a pre-connected cellular-enabled tablet for questionnaire answering. RPM data utilized real-time electronic health system integration and predetermined parameters to alert RPM nurses. Pre-specified escalation care pathways were then used to respond and escalate care, as necessary. The primary outcome of this pilot study was to assess the feasibility of implementing an RPM program in this patient population with a secondary outcome to determine the ability to detect ICI pneumonitis before significant clinical symptoms. Results: Sixteen patients were enrolled of whom 5 declined participation (2 due to inconvenience and 3 for unclear reasons) resulting in 11 patients who underwent monitoring. Five patients graduated monitoring without detection of ICI pneumonitis within a 4-month timeframe. Six patients are currently undergoing RPM. 372 alerts occurred of which 8 (2%) were escalated to physician review. These alerts included elevated heart rate in 4, shortness of breath in 3, and elevated blood pressure in 1. One patient was triaged to an emergency department and diagnosed with grade 2 ICI pneumonitis. Conclusions: We show that RPM in patients who are at high-risk for developing ICI pneumonitis can be effectively integrated into a care model and monitor pneumonitis related symptoms. Further studies are needed to prove whether RPM is beneficial in this population including other ICI toxicities.
Efficacy of next-generation genomic sequencing (NGS) applied to cerebrospinal fluid (CSF) in the identification of actionable mutations in Mexican patients.
Authors: González Espinoza Iván Romarico , Sánchez-Sosa Sergio , Castro-Ponce Abraham , Sandoval-Amaro Gabriela , Juárez-Salazar Gabriela , Nieva Ana Isabel , Íñiguez López Galo Ismael , Acosta Ponce de León Eric , Aranda Jorge Esteban , Garibay Diaz Julio Cesar , Chiquillo-Domínguez Mariana
Published: July 2024

e14000

Background: Among the benefits offered by NGS from liquid biopsy are the molecular classification of neoplasms as well as the identification of therapeutic targets, without the need to obtain a biopsy of the tumor when it is not feasible. Since 2016, the World Health Organization has included these biomarkers as part of its classification for better management. Additionally, in the case of metastatic tumors, it allows the identification of therapeutic targets as well as resistance mutations and even driver mutations to better understand their biology. In this study, we evaluated the efficacy of CSF NGS in the identification of actionable mutations in patients with CNS neoplasms, and its potential impact on the personalization of cancer treatments for patients in our center. Methods: A retrospective analysis of nine cases was performed in which CSF was used to identify NGS-actionable mutations, collecting, and descriptively analyzing clinical and molecular data from these patients. Results: Mean age was 51.89 years; 55.56% were men and 44.44% women; 66.67% had family history of cancer, of which 83.33% were first-degree relatives; 88.89% had neurological symptoms prior to the study; 33.33% were primary CNS tumors; 55.56% were secondary tumors metastatic to the CNS; 11.11% were indicated due to suspected CNS metastasis. At least 1 genomic alteration was found in 89% of the cases; the most frequently altered gene in primary tumors was TP53 (66.67%). In secondary tumors, the most frequently altered genes were AR and EGFR with 40% incidence each; Approved therapies were found in 55.56% of the cases, therapies approved in other neoplasms in 44.44%, and phase 2 or 3 clinical trials were available in 88.89%. Specific alterations found in are listed in the table. Survival rate at 6-month follow-up was 55.56%. Conclusions: In our patients, the study of CSF through NGS effectively identified actionable mutations with approved treatment in the analyzed neoplasms, other neoplasms, or clinical trials available for enrollment in most cases. In one case, it was possible to rule out the presence of metastasis in CNS, avoiding unnecessary toxicity. To our knowledge, this is the first study in our country that reports the findings of this technique in medical practice, however, more research is needed in bigger populations to optimize and validate the implementation of this study as part of the approach to patients with CNS tumors. [Table: see text]
Descriptive analysis of brain metastases (BM) of solid neoplasms in an academic hospital from a low- and middle-income country (LMIC) with a Hispanic population.
Authors: Dominguez-Porras Victor Antonio , De La Pena Lopez Ildefonso Roberto Roberto , Flores-Balcázar Christian Haydeé
Published: July 2024

e14015

Background: Multidisciplinary management of BM of solid cancers integrates different combinations of treatment modalities. The scarcity of SRS centers has prevented widespread adoption of this therapy for appropriately selected patients. Methods: One-hundred eighteen (51.7% female, 48.3% male, median age 59 years) BM patients from a National Health Institute from Mexico (INCMNSZ) were included and analyzed. Results: The most common primary tumors were lung and breast cancers (25 cases each, representing 21% of the whole cohort), kidney cancer (14%), male germ cell tumors (10%), metastatic carcinoma of unknown primary (CUP) (5%), upper- and lower- gastrointestinal cancers (5%), thyroid differentiated cancers (5%), followed by melanoma, prostate, ovarian, hepatobiliary cancers and sarcoma (3% each of them) and urothelial carcinoma (2%) being the least common. No biopsy was reported for only one case. The most common histomolecular tumors were adenocarcinoma of the lung (17 cases), renal cell carcinoma (17), triple negative (TN) breast cancer (BC) (9), HER-2+ BC (7), Nonseminomatous germ cell tumor (7), CUP (6), ER+/HER-2+ BC (5), Germ cell tumor with choriocarcinoma (5), small-cell lung cancer (SCLC) (5), melanoma (5), prostate adenocarcinoma (5), thyroid differentiated cancer not otherwise specified (NOS) (5). Rectal adenocarcinoma, high-grade serous ovarian cancer, ER+/PR+ BC, sarcomas and NSCLC (3 cases, each) and urothelial carcinoma (2). Rare tumor subtypes, with one case, each included hepatocellular carcinoma, PR+/HER2+ BC, follicular thyroid cancer, esophageal, gastric and colonic adenocarcinomas, neuroendocrine prostate, neuroendocrine gallbladder, endometrial, large cell neuroendocrine lung carcinomas and cholangiocarcinoma. A solitary BM was present in 44 patients (37.3%), 2-3 BM in 30 (25.4%) and >3 BM in 44 patients (37.3%). 18 patients (15.2%) were not symptomatic at the time of diagnosis. 79 patients were treated with Whole-Brain Radiotherapy (WBRT), ten with a combination of surgery and adjuvant WBRT, seven with surgical resection without radiotherapy, only five included SRS as part of their treatment and seventeen received only supportive care. There was no difference in overall survival (OS) between treatment modalities excluding supportive care (p=0.05). Conclusions: Our experience from a LMIC with Hispanic population highlights that more than 50% of BM metastasize from solid tumors different from lung and breast cancers. Even though SRS has been included in recent guidelines from ASCO and ESMO, WBRT is the option most commonly included in multimodality treatments.
Immunological profiling of glioblastoma cellular composition to predict response to dendritic cell vaccination.
Authors: Lepski Guilherme , Peres Nataly , Santos Patricia Bergami , Pinho Mariana , Chauca-Torres Nadia , Evangelista Gabriela Coeli , Teixeira Sarah , Flatow Elizabeth , de Oliveira Jaqueline Vaz , Fogolin Carla , Arévalo Analía Leonora , Alves Venâncio A , Barbuto Alexandre
Published: July 2024

e14037

Background: Glioblastomas are the most common primary malignant brain tumors, comprising 2% of all adult cancers. Despite recent advancements in genetic classification and targeted therapies for specific mutations, there has been no significant improvement in overall life expectancy for the majority of patients. Last year, our research group reported promising results from a phase II prospective trial involving allogeneic dendritic cell vaccination. To date, six out of 37 reported cases remain alive without tumor recurrence, exhibiting a performance status of 90 to 100% according to the Karnofsky Performance Scale (KPS) three years after the initiation of vaccination. Methods: In this study, we focused on the immune cell infiltration observed at the time of tumor excision in enrolled patients. We utilized flow cytometry to quantify cells expressing membrane CD86, CD45, HLA-DR, PD-L1, CD11b, and CD14, in addition to assessing IDH-1 status, age, gender, KPS, gender, ECOG, symptomatology, and the number of vaccines administered during the trial. Our goal was to predict responsiveness in terms of overall survival using a neural network prediction algorithm with three hidden nodes and five seeds for improved reproducibility. We employed the random holdback method for algorithm validation. Results: From the 37 enrolled patients, we successfully obtained viable tumor cells from 19 frozen samples. The model achieved an RSquare value of 0.71 after training and 0.66 after validation (where 1 indicates a perfect model and 0 implies no improvement over a constant model). Similar RSquare values in both training and validation sets indicate strong predictive power. Positive predictors of overall survival included HLA-DR positivity, PD-L1 positivity, IDH-1 mutation status, the presence of focal deficits, and higher KPS scores, while negative predictors were CD86 expression, older age, symptoms of intracranial hypertension (ICH), and higher ECOG performance status. Conclusions: In conclusion, the neural network algorithm described herein enables the prediction of responsiveness to dendritic cell vaccination in terms of overall survival, based on clinical features and the profile of immune cell infiltration observed at the time of tumor excision.
Prevalence and outcomes of acute kidney injury among hospitalized patients with gastric cancer: Insights from a National Inpatient Sample study (2018-2020).
Authors: Iqbal Rabia , Gaddam Mrunanjali , Bajwa Ahmad Taimoor , Jayakumar Jayalekshmi , Ginjupalli Manasa , Kumar Vikash , Nanavaty Dhairya , Colon Ramos Ana , Clement Jincy
Published: July 2024

e16124

Background: Acute kidney injury (AKI) occurs in 50-60% of the patients admitted to the hospitals, and up to almost 20% of those patients have underlying cancer. AKI has been associated with high mortality and adverse outcomes in cancer patients. This relationship between cancer and kidney health, known as "the kidney-cancer connection has attracted considerable interest in research circles. In this study, we aimed to evaluate the outcome of AKI in hospitalized patients with gastric cancer. Methods: A retrospective analysis was conducted using the National Inpatient Sample database from 2018 to 2020 and the ICD- 10 codes to identify the patients > 18 years old with the principal diagnosis of Gastric Cancer. We evaluated the effect of acute kidney injury (AKI) on mortality, morbidity outcomes, and resource usage in patients with gastric cancer. Categorical variables underwent comparison using the chi-square test, while continuous variables were compared using the t-test. Multivariate analysis was conducted to derive the odds ratio, and all weighted analyses were carried out using STATA. Results: We identified a total of 123,935 patients with a primary diagnosis of gastric cancer who were hospitalized between 2018 and 2020 in the United States. Out of them, 20% (24,787) of the patients had developed acute kidney injury during the hospital admission. The mean age of the patients was 69 years. Of these patients, 67% were male, and the remaining 33% were female. The mortality for gastric cancer patients with AKI was 18.3%, while it was 4.7% for patients without AKI. After adjusting for confounders, AKI had higher odds of mortality (Adjusted odds ratio [aOR] for mortality 4.41, 95% confidence interval [CI]: 3.96-4.91, P < 0.001). AKI was also associated with higher resource utilization, including a higher length of stay (LOS) (mean LOS increased by 9.5 days vs 6.5 days in patients without AKI) and higher hospital charges (by $127,814). Conclusions: Our study concludes that the patients with gastric cancer who developed Acute Kidney Injury during the hospital stay had worse outcomes. Identifying AKI early on can help with timely intervention, which can reduce adverse outcomes. Thus it is extremely important for nephrologists and oncologists to closely monitor patients' renal function throughout their treatment.[Table: see text]
Discovering urinary protein biomarkers for hepatocellular carcinoma in the population of patients with chronic hepatitis B: A single-center case-control study.
Authors: Zhang Yuke , Huang Yongfa , Xing Jiali , Wang Yuxin , Jin Bao , Xue Runze , Guo Ye , Chang Xiaoyan , Guan Mei , Liu Xiao , Wan Xueshuai , Zhao Hong , Hong Zhixian , Xu Haifeng , Wu Jianqiang , Mao Yilei , Du Shunda
Published: July 2024

e16230

Background: Chronic hepatitis B (CHB) can result in hepatocellular carcinoma (HCC) imposing a substantial health and economic burden worldwide. Early detection of hepatitis B virus-related HCC (HBV-HCC) in CHB with potential biomarkers has emerged as an urgent and challenging task. Recent progression of urinary proteomics provides a promising method for HBV-HCC biomarker discovery. Methods: This single-center case-control study, conducted at Peking Union Medical College Hospital, enrolled 33 patients with HBV-HCC, 26 patients with CHB, 30 healthy controls, and 33 controls with other types of cancer. Urine proteomes were analyzed using liquid chromatography with tandem mass spectrometry by data-dependent acquisition or parallel reaction monitoring, respectively. Differential analysis was carried out with limma package in R software, and the origin of selected proteins was confirmed with immunohistochemistry of surgical specimens. The diagnostic performance of the biomarker panel was evaluated with area under receiver operator curves (AUROC). Results: 21 urinary proteins were significantly upregulated in HBV-HCC compared with CHB samples, playing key roles in vesicular transportation, cytoskeleton-extracellular matrix interaction, and tumor development according to enrichment analysis. Immunohistochemistry validated the differential expression of 4 urinary proteins (4UP: HNRNPM, ADGRG1, APOC1, and RALA) across cancerous and adjacent normal liver tissues. These proteins were specifically found in HBV-HCC but not in CHB, healthy control, or other cancer controls. The AUROCs of 4UP individually (0.642 for APOC1, 0.780 for HNRNPM, 0.755 for ADGRG1, 0.729 for RALA) were no worse than that of serum α-fetoprotein (AUROC = 0.751), and the 4UP panel unified via logistic regression showed an AUROC of 0.828. Conclusions: Urinary proteomics revealed HNRNPM, ADGRG1, APOC1, and RALA as biomarkers to distinguish HBV-HCC from CHB. The 4UP could be traced back to HBV-HCC tumor cells, shedding light on pathogenesis of HBV-HCC. [Table: see text]
An analysis of the evidence underpinning the surgical treatment of hepatocellular carcinoma.
Authors: Radi Imad , Zhan-Moodie Samantha , Scanlan Luke , Sapkalova Viktoriya , Resheek Nerella , Mehra Mehul , Colquhoun Steven , Yakoub Danny
Published: July 2024

e16278

Background: The American Association for the Study of Liver Diseases (AASLD) and National Comprehensive Cancer Network (NCCN) guidelines on Hepatocellular Carcinoma (HCC) surgery are based on evidence from many different systematic reviews (SRs) and meta-analyses (MAs). Quality of these studies needs to be standardized. Methods: SRs and MAs cited in AASLD and NCCN HCC (2023) surgery guidelines were collated by two independent reviewers. An independent third reviewer acted as tie-breaker when necessary. The standardized assessment tools, the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Assessing the Methodological Quality of Systematic Reviews (AMSTAR) were used to evaluate the quality of these studies. Quality of studies was determined based on adherence to items of the checklist. The PRISMA and AMSTAR checklists consist of 41 and 16 items, respectively. Results: Overall, 13 studies were identified, 9 from AASLD guidelines and 4 from the NCCN. Studies were published between 2007 and 2023, with 38% being published in the last 5 years. Studies had an average of 23,829 patients. Many of the studies (71%) reported use of the PRISMA checklist, but no studies cited the AMSTAR checklist. Studies had an average adherence of 68% to the PRISMA checklist, with a median of 76% (range 17-88%). 23% of studies adhered to less than half of the PRISMA checklist. Looking at the AMSTAR checklist, studies had an average adherence of 51%, with a median of 56% (range 4-72%). 31% of studies adhered to less than half the AMSTAR checklist. Adherence was lowest in items involving availability and accessibility of protocols, assessing risk of bias, and transparency of protocols. Additionally, no papers reported funding sources of their reviewed articles. Conclusions: There is significant room for improvement in MAs and SRs about HCC surgical management. Many quoted studies needed more rigorous methodology and quality control for conducting and reporting. It is important to fully investigate and communicate the biases present in MAs and SRs to readers. PRISMA and AMSTAR checklists can be used when reviewing and selecting evidence for future guideline development to offer the most complete and transparent understanding of data presented.
Influence on surgical approach in hepatocholangiocarcinoma: A demographic and socioeconomic analysis.
Authors: Al Kurnas Mohammed , Becker Ashley , Wu Xinxin , Silberstein Peter T.
Published: July 2024

e16280

Background: Hepatocholangiocarcinoma (HCC-CC) is a rare and aggressive malignancy of the liver that contains histopathological features of both hepatocellular carcinoma and cholangiocarcinoma. Surgery is the mainstay of treatment, and the surgical approaches used include radical hepatic resection, laparoscopic, and robotic surgery. There has yet to be a study that explores the impact of demographic features on the choice of surgical modality in patients with HCC-CC. The National Cancer Database (NCDB) was analyzed to determine the effects of demographic features on surgical modality and overall survival. Methods: A retrospective cohort analysis utilizing the NCDB included 2,449 patients diagnosed with HCC-CC (ICD-8180/3) between 2004-2020. Surgical modality was categorized into either open or minimally invasive by the preliminary treatment. Minimally invasive techniques included robotic-assisted and minimally invasive. Race, sex, age at diagnosis, income level, insurance used, distance from the facility, and the status of the facility as an academic center on the surgical modality were compared using Pearson Chi-squared tests or independent samples t-test as pertinent. Multivariate analysis with binary logistic regression was used to analyze the following categorical variables in relation to choice of surgical modality: race, sex, income, insurance, sex, and facility type. Surgical treatment modality on overall survival was analyzed by the Kaplan-Meier method. Exclusion criteria included missing data. Results: Most cases analyzed were White (75.8%), male (67.5%), and had government insurance as the primary payor at diagnosis (60.6%). Of the cases analyzed, 625 underwent surgery (25.5%). Patients who underwent minimally invasive surgery were more likely to be government-insured than patients who underwent open surgery (69.8% vs. 55.6%, P < 0.05). Patients who underwent open surgery were younger on average (61.4 vs. 66.0 years, P < 0.05). There was no significant difference in distance from residence to the treatment facility between the two surgical approaches. Multivariate analysis showed that patients treated at academic centers were less likely to receive minimally invasive surgery (28.1%) over open surgery (71.9%; P = 0.041, 95% CI 0.469-0.985) without statistical significance for race, sex, income, or insurance. The average survival time was significantly longer in open vs minimally invasive surgery (67.9 vs. 55.3 months, P < 0.05). Conclusions: We identified that patients who underwent open surgery had significantly better overall survival with an average difference of 12.6 months. Even after accounting for other factors, the choice of surgical modality was significantly influenced by treatment at an academic institution. Patients receiving care at an academic facility are more likely to receive open surgery leading to overall increased survival.
Quality of life (QoL) benefits following 177Lu-DOTATATE therapy in patients (pts) with 68Ga-DOTATATE PET positive primary site agnostic neuroendocrine tumors (NET).
Authors: Wong Rebecca KS , Myrehaug Sten , Juergens Rosalyn A. , Laidley David , Ezzat Shereen , Beauregard Jean-Mathieu , Levine Oren Hannun , Veit-Haibach Patrick , Metser Ur , Driscoll Brandon , Shessel Andrea , Yeung Ivan , Mesci Aruz , Publicover Julia , Sun Edward , Lajkosz Katherine
Published: July 2024

e16291

Background: The QoL experience during the 1st year of follow up for 68Ga-DOTATATE PET positive primary site agnostic pts with progressive metastatic NET enrolled in a prospective single arm clinical trial of 177Lu-DOTATATE therapy (OZM 067) is described here. Methods: Pts with progressive NET, Ki67 Index < 30%, adequate organ function & ECOG £2 were eligible. Only pts demonstrating positive disease (Krenning score 3-4) on 68Ga-DOTATATE PET were eligible to proceed to 177Lu-DOTATATE therapy (4 cycles at 8- to 12- week intervals. Primary outcome was progression free survival (PFS) at 12 mths. QoL (EORTC QLQ 30 and GINET21) at baseline, 6, 12, 18, 24, 30 months were recorded. Summary scores at time point of interest, and their change from baseline were estimated using a mixed model repeated measure, with baseline assessment included in the model as covariate. Data were normalized with a range of 0-100. A positive change score for Global Summary Status, Functioning Domains, and a negative change score for Symptom Scales and Items represent improvement. A ≥5 point change score is used as a threshold for Minimal Clinically Important Difference (MCID). Results: 195 pts were enrolled. 13 pts were 68Ga-DOTATATE PET negative while 5 pts withdrew consent. 177 pts received at least one dose of 177Lu-DOTATATE. All pts enrolled were eligible for a minimum of 12 mths follow up at time of data lock. The primary site was GEPNET in 143 (81%) and non GEPNET in 34 (19%). At 12 mths, the median follow-up was 33 (range 3-71) mths. PFS and OS were 81 (95% CI: 75-86)% and 92 (87-95)% respectively. QoL data at the following timepoints baseline, 6 & 12 (±2) mths were available in 174,128 & 111 pts respectively. The top three symptoms captured in EORTC QLQ 30 was Fatigue (32.5 SD 23.8) , Insomnia (26.7 SD 28.1) and Diarrhea (22.1 SD 29.4). At 12 mths, an improvement in mean score of ≥MCID in Global Health status (GHS) (+5.4), Role Fc Scale (+7,1), Social Fc Scale (+8.7) and multiple symptoms (Fatigue, Pain, Appetite, Constipation, Diarrhea, Financial Difficulties), Sexual fc, Social, Body image (Table 1) were captured. Conclusions: Patients with primary site agnostic 68Ga-DOTATATE PET positive NET experienced improvement in multiple quality of life domains including multiple symptoms post 177Lu-DOTATATE at 12 mths. Sexual fc and body image had the largest improvement. Clinical trial information: NCT02743741 . [Table: see text]
A reassessment of the clinical utility of 68Ga-DOTATATE PET/CT in patients with gastroenteropancreatic neuroendocrine tumors.
Authors: Prela Orjola , Caveney Brennen , Strawderman Myla S. , Carpizo Darren R.
Published: July 2024

e16294

Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a rare and biologically diverse group of tumors that can be challenging to image. Gallium-68 (Ga-68) DOTATATE positron emission tomography/computed tomography (PET/CT) is the most sensitive imaging tool for these tumors and has now been in clinical practice for over a decade. While its use has increased over time, its clinical impact remains unclear for specific stages of disease and indications for imaging. We sought to investigate this to provide information to guide its future use in clinical management. Methods: This retrospective cohort study identified adults with pathologically confirmed GEP-NETs between 1/1/2020 and 9/1/2022 at a tertiary care academic medical center. The electronic medical record was reviewed for demographic, clinical, and radiographic data. The primary objective was to determine if the use of 68Ga-DOTATATE PET/CT was associated with a change in clinical management, medical or surgical. The secondary objective was to determine if 68Ga-DOTATATE PET/CT was more effective in identifying primary or metastatic lesions compared to traditional imaging such as CT or magnetic resonance imaging (MRI) performed less than 90 days of the PET/CT scan. Percentages are reported with 95% Confidence Intervals (CI). Results: Overall, 124 patients with pathologically confirmed GEP NETs underwent a total of 207 68Ga-DOTATATE PET/CT scans. The majority (92.7%) of GEP NETs were moderately/well differentiated and the primary sites included the small intestine (50%), pancreas (23.4%), appendix/colon (8.9%), gastric (8.1%), mesentery (2.4%), and unknown (7.3%). Following PET/CT scan, 51 patients (41.1%; 95% CI = 32.4-49.8) had a change in clinical management, with the proportion of patients who had a change being higher among those with metastatic disease (44.9% vs 14.5%). Of the 124, 72 patients had traditional imaging 90 days or less prior to PET/CT available for comparison. In this subgroup, 34 patients (47.2%; 95% CI = 35.7-58.7) had new lesions identified on PET/CT that were not identified using traditional imaging and of the 34 patients with new lesions identified, 79.4% (95% CI = 66-93) had a change in their clinical management. The majority of these patients had M1 disease (50% vs 15.4%). Conclusions: This study highlights the impact of 68Ga-DOTATATE PET/CT imaging in the clinical management of patients with gastroenteropancreatic neuroendocrine tumors (GEP NETs). Notably this imaging technique resulted in a change in clinical management for 41% of these patients, particularly benefiting those with metastatic (M1) disease, where the change in management was more pronounced (44.9% vs. 14.5%). Furthermore, 68Ga-DOTATATE PET/CT proved superior to traditional imaging revealing new lesions in 47.2% of the patients, with the majority being patients with metastatic disease.
Impact of EOB-MRI on the outcome of patients with pancreatic cancer in real-world settings.
Authors: Oba Atsushi , Taguchi Tomoyuki , Fujikawa Naoto , Okami Suguru , Tsuji Takashi , Michel Alexander , Kado Yuki , Goshima Satoshi
Published: July 2024

e16298

Background: Contrast-enhanced computed tomography (CE-CT) is a commonly used imaging modality for the preoperative detection of local extension and distant metastasis in patients (pts) with pancreatic cancer (PaC). There have been cases where surgical treatment was deemed unsuitable due to unexpected distant metastases discovered during surgery, which had not been detected by CE-CT. While studies have reported gadoxetate disodium-enhanced MRI (EOB-MRI) improves the detection of liver metastases, it is not clear whether adding EOB-MRI to CE-CT provides clinical benefits, e.g. improved outcomes through the early access to appropriate treatments by avoiding unnecessary surgery (open-close surgery) in pts with PaC. This study aimed to assess the effectiveness of adding EOB-MRI before surgical or non-surgical treatment on overall survival (OS) in pts with PaC in real world settings. Methods: This was a retrospective cohort study using a nationwide hospital-claims database in Japan. Pts aged ≥18 years diagnosed with PaC with a record of surgery, radiotherapy, or chemotherapy, who had an imaging modality were identified between January 1, 2011 to October 31, 2021. Pts were grouped into EOB-MRI and no EOB-MRI groups, and further grouped into surgery, no surgery and open-close laparotomy. OS was compared between propensity-score matched EOB-MRI and no EOB-MRI groups using the Cox regression model. Results: 39,624 pts were included in the study, of them, 4,477 (11.3%) underwent EOB-MRI prior to the initial treatment. 2,061 (46.0%) pts in EOB-MRI group underwent surgery, 2,346 (52.4%) had no surgery and 70 (1.6%) had open-close laparotomy. In 35,147 (88.7%) pts in no EOB-MRI group, 13,182 (37.5%) underwent surgery, 21,506 (61.2%) had no surgery, and 459 (1.3%) had open-close laparotomy. The OS results in subgroups are shown in the Table. Conclusions: In real-world settings, EOB-MRI performed prior to the initial treatment was associated with significantly higher OS than those without EOB-MRI in pts who did not undergo surgery, but there was no difference in OS in pts who underwent surgery. These results suggest that the early detection of micro hepatic metastases through EOB-MRI and multidisciplinary treatment that enables EOB-MRI may contribute to improved outcomes in pts with PaC. [Table: see text]
Unveiling the nexus: Use of e-frailty index in predicting chemotherapy tolerance in older patients with pancreatic cancer.
Authors: Al-Jumayli Mohammed , Sehovic Marina , Vonnes Cassandra , Extermann Martine
Published: July 2024

e16315

Background: Pancreatic cancer prevalence is on the rise, particularly among octogenarians—individuals aged 80 years and above. This age group, however, remains notably underrepresented in clinical trials, hindering the applicability of findings to this growing demographic. Methods: We conducted a retrospective study investigating the predictive potential of the E-frailty Index (EFI) in relation to chemotherapy tolerance in octogenarian patients with unresectable/metastatic pancreatic adenocarcinoma. Drawing from EFI's developmental insights in a prior study¹, our cohort comprised 72 octogenarians undergoing chemotherapy. Results: Despite a modest statistical correlation (R = 0.038, p = 0.751), our study revealed a weak, but positive association between EFI and chemotherapy toxicity. Conclusions: Our findings, while subtle, highlight the potential relevance of EFI in predicting chemotherapy outcomes among octogenarians. The non-significant correlation underscores the need for larger-scale, prospective trials to confirm these insights. Inconclusion, This study, rooted in the developmental continuum of EFI, offers a glimpse into its potential significance in predicting chemotherapy tolerance in octogenarian pancreatic cancer patients. The call for prospective trials is evident, especially considering the underrepresentation of this demographic in current research.
A preliminary enrichment analysis of tumor genes in patients suffering from rectal cancer with and without CNS metastasis.
Authors: Polyak Andrew , Cholankeril Michelle
Published: July 2024

e16381

Background: Colorectal cancers have been touted as the third most common cancer and the third leading cause of cancer death worldwide. Of these, rectal cancers often have a more favorable outcome, and are generally responsive to chemotherapy and radiation, due to metastasis limited to local tissues via lymphatics. However, in recent years, cases of rectal cancer with distant metastasis to the CNS have been noted at an urban community hospital serving a primarily Hispanic population in central New Jersey. Methods: We used genetic data from 51 patients at our local cancer center over 5 years to delineate risk factors associated with CNS metastasis. Of these patients, two had CNS metastasis with available tumor genetic information. We performed a gene enrichment analysis to determine phenotypic terms and molecular pathways associated with each gene set using Enrichr. Results: Of 51 patients, genetic data was available on 20, of which 18 had rectal cancer without CNS metastasis. Mutations involving 23 genes were found in this cohort, analysis of which found enrichment of the terms “Lynch Syndrome” and “Constitutional mismatch repair deficiency syndrome”, which are classically implicated in CRCs. In addition, enrichment of the terms “rectal cancer childhood”, “colorectal cancer childhood”, and “Familial colorectal cancer” were found. Of the two patients who had metastasis to the CNS, mutations involving 14 genes were found. Interestingly, both patients had mutations involving KRAS. Analysis of these genes found enrichment of the terms “pilomyxoid astrocytoma”, “giant cell glioblastoma” and “gliosarcoma”. Interestingly, common to both cohorts were the classic CRC-associated genes KRAS, APC and TP53, further solidifying their role in general CRCs. Conclusions: While this study is ongoing, preliminary data suggest that genetic analysis of tumors in patients with rectal cancer can determine whether a patient is susceptible to CNS metastasis. Given the heterogeneity of these cancers, further studies involving tumor and germ-line genetic analysis, which follow patients longitudinally may benefit in predicting which tumors are prone to CNS metastasis before they metastasize.
Lutetium-177–PSMA-617 experience in Appalachian patients with advanced prostate cancer at West Virginia University Health Science Center.
Authors: Yu Stephen Lee , Holler Seth , Wen Sijin , Wang Xiaofei , Hogan Thomas F.
Published: July 2024

e17045

Background: Lutetium Lu-177 vipivotide tetraxetan (Lu-177) allowed for improved biochemical and radiographic response rate with relatively low toxicity for metastatic castration-resistant prostate cancer (PC) after multiple lines of therapy. In the 2021 VISION study (DOI: 10.1056/NEJMoa2107322), Lu-177 was reported to have a median overall survival (OS) of 15.3 months in patients (pts) with advanced prostate cancer (PC). We reviewed the result with Lu-177 for the treatment of advanced PC at a rural tertiary academic center at West Virginia University Health Science Center (WVU-HSC). Methods: All PC pts receiving one or more doses of Lu-177 at WVU-HSC were retrospectively reviewed. Pts were followed until death or the last clinic visit. All pts were established patients at WVU-HSC for management of the advanced PC between July 2022 and February 2024. Data was tabulated with descriptive statistics and median survival was calculated from Kaplan-Meier method. Results: Over an eighteen months period 34 pts received 126 doses of Lu-177. 26 pts were referred from outside the WVU-HSC specifically for Lu-177. Demographics from data collection showed predominantly Caucasian pts (91% Caucasian). The time from the initial PC diagnosis to the first dose of Lu-177 was a median of 67 months (range: 10 months-367 months). The median age at the first dose of Lu-177 was 65 years (range: 45-80). 18 patients (53%) remain alive as of Feb 2024. 14 pts (41%) completed 6 cycles of Lu-177 and 11 pts (32%) remain alive. The Kaplan-Meier median OS for these 34 pts starting from the first cycle of Lu-177 was 10 months. Conclusions: A 2022 estimated cost for Lu-177 was $42,500 per dose (excludes administration) so “payors” may have been charged more than $5,000,000 for the Lu-177 for these patients. Lu-177 may be of more benefit earlier in the PC disease spectrum, or perhaps pre-treatment PSMA imaging can better target patients who will benefit from Lu-177. Our observed median OS of 10 months did not match the 15.3 reported in the VISION study (DOI: 10.1056/NEJMoa2107322). Further data evaluation and collection are warranted from different communities to investigate the differences observed in the survival data reported in the literature and observed in the clinic setting. [Table: see text]