Texas MD Anderson Cancer Center Research Articles

Accuracy of pre-operative tumor size assessment compared to final pathology and frequency of adjuvant treatment in patients with FIGO 2018 stage IB2 cervical cancer

ObjectiveThe primary aim of our study was to compare tumor size assessment by pre-operative evaluation (physical examination and/or imaging) with tumor size on final pathology. As a secondary outcome, we...

MicroRNAs are enriched at COVID-19 genomic risk regions, and their blood levels correlate with the COVID-19 prognosis of cancer patients infected by SARS-CoV-2

BackgroundCancer patients are more susceptible to an aggressive course of COVID-19. Developing biomarkers identifying cancer patients at high risk of COVID-19-related death could help determine who needs early clinical intervention. The miRNAs hosted in the genomic regions associated with the risk of aggressive COVID-19 could represent potential biomarkers for clinical outcomes.Patients and methodsPlasma samples were collected at The University of Texas MD Anderson Cancer Center from cancer patients (N = 128) affected by COVID-19. Serum samples were collected from vaccinated healthy individuals (n = 23) at the Municipal Clinical Emergency Teaching Hospital in Timisoara, Romania. An in silico positional cloning approach was used to identify the presence of miRNAs at COVID-19 risk-associated genomic regions: CORSAIRs (COvid-19 RiSk AssocIated genomic Regions). The miRNA levels were measured by RT-qPCR.ResultsWe found that miRNAs were enriched in CORSAIR. Low plasma levels of hsa-miR-150-5p and hsa-miR-93-5p were associated with higher COVID-19-related death. The levels of hsa-miR-92b-3p were associated with SARS-CoV-2 test positivity. Peripheral blood mononuclear cells (PBMC) increased secretion of hsa-miR-150-5p, hsa-miR-93-5p, and hsa-miR-92b-3p after in vitro TLR7/8- and T cell receptor (TCR)-mediated activation. Increased levels of these three miRNAs were measured in the serum samples of healthy individuals between one and nine months after the second dose of the Pfizer-BioNTech COVID-19 vaccine. SARS-CoV-2 infection of human airway epithelial cells influenced the miRNA levels inside their secreted extracellular vesicles.ConclusionsMiRNAs are enriched at CORSAIR. Plasma miRNA levels can represent a potential blood biomarker for predicting COVID-19-related death in cancer patients.

Molecular and Clinical Features of Pancreatic Acinar Cell Carcinoma: A Single-Institution Case Series

Objectives: Acinar cell carcinoma (ACC) accounts for about 1% of pancreatic cancers. The molecular and clinical features of ACC are less characterized than those of pancreatic ductal adenocarcinoma. Methods: We retrospectively evaluated the clinical and molecular features of ACC patients who underwent germline and/or somatic molecular testing at The University of Texas MD Anderson Cancer Center from 2008 to 2022 and two cases from 2023–2024 who underwent RNA and TME analysis by Boston Gene. Patient information was extracted from our institutional database with the approval of the Institutional Review Board. Results: We identified 16 patients with available molecular testing results. Fourteen patients had metastatic disease, one had borderline resectable disease, and one had localized resectable disease at diagnosis. Fifteen patients were wild type for KRAS (one patient had unknown KRAS status). Somatic/germline mutations of DNA damage repair genes (BRCA1/2, PALB2, and ATM) were present in 5 of 12 patients tested for these genes. One patient was found to have RET fusion and responded favorably to selpercatinib for over 42 months. The median overall survival (OS) was 24 months for patients with metastatic disease. One of the additional two cases who underwent BostonGene testing was found to have NTRK1 fusion. RNA and TME analysis by Boston Gene of the two cases reported immune desert features and relatively lower RNA levels of CEACAM5, CD47, CD74, and MMP1 and higher RNA levels of CDH6 compared with PDAC.

Optimal Timing of Organs-at-risk-sparing Adaptive Radiation Therapy for Head-and-neck Cancer under Re-planning Resource Constraints.

Prior work on adaptive organ-at-risk (OAR)-sparing radiation therapy has typically reported outcomes based on fixed-number or fixed-interval re-plannings, which represent a one-size-fits-all approach and do not account for the variable progression of individual patients' toxicities. The purpose of this study was to determine the personalized optimal timing for re-planning in adaptive OAR-sparing radiation therapy, considering limited re-planning resources, specifically for patients with head and neck cancer (HNC). A novel Markov decision process (MDP) model was developed to determine optimal timing of re-plannings based on the patient's expected toxicity, characterized by normal tissue complication probability (NTCP), for four toxicities. The MDP parameters were derived from a dataset comprising 52 HNC patients treated at the University of Texas MD Anderson Cancer Center between 2007 and 2013. Optimal re-planning strategies were obtained when the permissible number of re-plannings throughout the treatment was limited to 1, 2, and 3. The MDP (optimal) solution recommended re-planning when the difference between planned and actual NTCPs (ΔNTCP) was greater than or equal to 1%, 2%, 2%, and 4% at treatment fractions 10, 15, 20, and 25, respectively, exhibiting a temporally increasing pattern. The ΔNTCP thresholds remained constant across the number of re-planning allowances (1, 2, and 3). The MDP model determines the optimal timing for implementing patient-specific adaptive re-planning. This approach incorporates ΔNTCP thresholds and considers varying total re-plannings. The methods are versatile and applicable across cancer types, institutional settings, and different OARs and NTCP models.

12255 Brain GFRAL Signaling Mediates Chemotherapy-Induced Fatigue And Cognitive Impairment In Mice

Abstract Disclosure: R. Dantzer: None. Brain GFRAL Signaling Mediates Chemotherapy-Induced Fatigue and Cognitive Impairment in Mice Brandon Chelette, PhD, Anand Singh, PhD, Robert Dantzer, DVM, PhDDept. of Symptom Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA Fatigue and cognitive impairments are commonly reported by cancer patients undergoing chemotherapy. The mechanisms of these neurotoxicities are still obscure. We hypothesize that they are mediated by mitokines that are released by cells undergoing mitochondrial stress in response to chemotherapy. For the present study, we have focused on growth differentiation factor 15 (GDF15) which acts in the brain by activating its receptor, GDNF family receptor alpha-like (GFRAL). Chemotherapy-induced fatigue was assessed by reduced voluntary wheel running. Cognitive impairment was assessed by altered performance in the Puzzle Box Test that measures executive function. We first checked whether commonly used chemotherapeutic drugs can induce GDF15. Mice were injected with cisplatin, paclitaxel, or bortezomib, and their effects on plasma levels of GDF15 were measured 24 h after (ELISA). Cisplatin was used in the following experiments in the form of one or two cycles of daily injections for five days with a rest of five days between cycles. To determine whether GFRAL mediates the effects of cisplatin on wheel running and performance in the puzzle box, mice were injected with a neutralizing antibody targeted to GFRAL (GFRALna) during or after cisplatin treatment. All studies were carried out in male and female C57BL/6 J mice using a 2 (+ chemotherapy) x 2 (+ GFRALna) factorial design with a minimum of 6 mice/group. Mitochondrial dysfunction was measured via Seahorse XF Analyzer Mito Stress Test. To determine whether activation of the GDF15/GFRAL axis recruits a central GDF15 compartment, Gdf15 mRNA was measured by qRT-PCR in the brain parenchyma, meninges, and choroid plexus. All the chemotherapeutic agents we tested induced statistically significant increases in circulating GDF15. GFRALna administered during cisplatin treatment (prevention) or after completion of cisplatin treatment (cure) abrogated cisplatin-induced decrease in wheel running and the deficit displayed by cisplatin-treated mice in the first hard trial run in the puzzle box. GFRALna also blocked the decrease in maximal oxygen consumption rate of mitochondrial in synaptosomes from cisplatin-treated mice. Cisplatin did not induce Gdf15 mRNA in the brain parenchyma but increased its expression in the meninges and choroid plexus. Although the role of this GDF15 brain compartment in the neurotoxicity of cisplatin remains to be determined, the present findings can be interpreted to suggest that GDF15-GFRAL signaling represents a new target for the treatment of chemotherapy-induced fatigue and cognitive impairment. Count: 2,246 characters Presentation: 6/1/2024

Likelihood adaptively incorporated external aggregate information with uncertainty for survival data.

Population-based cancer registry databases are critical resources to bridge the information gap that results from a lack of sufficient statistical power from primary cohort data with small to moderate sample size. Although comprehensive data associated with tumor biomarkers often remain either unavailable or inconsistently measured in these registry databases, aggregate survival information sourced from these repositories has been well documented and publicly accessible. An appealing option is to integrate the aggregate survival information from the registry data with the primary cohort to enhance the evaluation of treatment impacts or prediction of survival outcomes across distinct tumor subtypes. Nevertheless, for rare types of cancer, even the sample sizes of cancer registries remain modest. The variability linked to the aggregated statistics could be non-negligible compared with the sample variation of the primary cohort. In response, we propose an externally informed likelihood approach, which facilitates the linkage between the primary cohort and external aggregate data, with consideration of the variation from aggregate information. We establish the asymptotic properties of the estimators and evaluate the finite sample performance via simulation studies. Through the application of our proposed method, we integrate data from the cohort of inflammatory breast cancer (IBC) patients at the University of Texas MD Anderson Cancer Center with aggregate survival data from the National Cancer Data Base, enabling us to appraise the effect of tri-modality treatment on survival across various tumor subtypes of IBC.

Pregnancy-associated melanoma (PAM): A single institution retrospective review between 2005 and 2023.

30 Background: Melanoma is the most prevalent cancer during pregnancy, representing 31% of all gestational cancers, with its incidence rates rising globally. Pregnancy-associated melanoma (PAM) presents unique challenges in diagnosis and management due to maternal physiological and hormonal changes, as well as consideration of fetal impact. This study aims to understand the impact of pregnancy on melanoma outcomes to optimize patient care. Methods: We conducted a retrospective study of patients diagnosed with PAM at The University of Texas MD Anderson Cancer Center between 2005 and 2023. Eligible patients were diagnosed either during pregnancy or within one year of delivery. Frequencies and percentages were used to describe the study population. Our primary outcome was to describe melanoma characteristics and prognosis, and our secondary outcome was to investigate melanoma’s impact on obstetrical outcomes. Results: The study included 76 patients with a mean age of 31.3 ± 4.4 years, 93.4% of whom were of white or Caucasian origin. The median follow-up was 39.8 months. Diagnoses included Stage 0 (7.9%), Stage I (36.8%), Stage II (3.9%), Stage III (22.4%), and Stage IV (25%) melanoma. The mean Breslow Thickness was 2.1± 4.7 mm. Primary diagnoses occurred in 76.6% of patients, while 21.9% experienced recurrent episodes during pregnancy. At the time of their PAM event, 47.4% had localized disease, and 48.7% had metastatic disease. The average mean time from diagnosis to first surgery was 2.1 months in patients diagnosed during pregnancy (group 1) and 0.9 months in patients diagnosed after pregnancy (group 2). The average time from diagnosis to systemic therapy was 3.3 ± 2.8 months in group 1 and 1 ± 0.7 months in group 2. Patients diagnosed during pregnancy had an average gestational age of 17.8 weeks: 30.65% were diagnosed in the first trimester, 54.84% in the second, and 14.52% in the third trimester. Thirty-three (43.4%) patients had term deliveries, while fifteen (19.7%) patients gave birth prematurely. There were 75.0% live births, 5.3% spontaneous abortions and 3.9% elective terminations. Conclusions: Our findings contribute to the limited literature on PAM outcomes, emphasizing the importance of a collaborative approach in managing these patients. Close surveillance of pregnant patients with melanoma is essential to prevent treatment delays and ensure optimal maternal and fetal outcomes.

A bibliometric analysis of the application of the PI3K-AKT-mTOR signaling pathway in cancer.

PI3K-AKT-mTOR plays as important role in the growth, metabolism, proliferation, and migration of cancer cells, and in apoptosis, autophagy, inflammation, and angiogenesis in cancer. In this study, the aim was to comprehensively review the current research landscape regarding the PI3K-AKT-mTOR pathway in cancer, using bibliometrics to analyze research hotspots, and provide ideas for future research directions. Literature published on the topic between January 2006 and May 2023 was retrieved from the Web of Science core database, and key information and a visualization map were analyzed using CiteSpace and VOSviewer. A total of 5800 articles from 95 countries/regions were collected, including from China and the USA. The number of publications on the topic increased year on year. The major research institution was the University of Texas MD Anderson Cancer Center. Oncotarget and Clinical Cancer Research were the most prevalent journals in the field. Of 26,621 authors, R Kurzrock published the most articles, and J Engelman was cited most frequently. "A549 cell," "first line treatment," "first in human phase I," and "inhibitor" were the keywords of emerging research hotspots. Inhibitors of the PI3K-AKT-mTOR pathway and their use in clinical therapeutic strategies for cancer were the main topics in the field, and future research should also focus on PI3K-AKT-mTOR pathway inhibitors. This study is the first to comprehensively summarize trends and development s in research into the PI3K-AKT-mTOR pathway in cancer. The information that was obtained clarified recent research frontiers and directions, providing references for scholars of cancer management.

Biomarker trajectory for earlier detection of lung cancer

To determine whether an algorithm based on repeated measurements of a panel of four circulating protein biomarkers (4MP) for lung cancer risk assessment results in improved performance over a single time measurement. We conducted data analysis of the 4MP consisting of the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19 fragment in pre-diagnostic sera from 2483 ever-smoker participants (389 cases and 2094 randomly selected non-cases) in the Prostate, Lung, Colorectal, Ovarian (PLCO) Study who had at least two sequential blood collections over 6 years. A parametric empirical Bayes (PEB) algorithm, which incorporates participant biomarker history at each time point, was compared to a single-threshold (ST) method. Among ever-smoker participants, the PEB approach yielded an additional 4% improvement in the AUC compared to the ST approach (P-value: 0.009). When considering an ≥10 PY smoking history and at a fixing the specificity corresponding to 1% 6-year lung cancer risk, PEB resulted in significant improvement in the sensitivity (SenPEB:96.3% vs SenST:91.0%; P-value: 6.7e-3). The PEB algorithm identified 17 of the 35 cases that remained ST negative, at an average of 1.26 years before diagnosis. Ten case individuals who were positive based on ST at an average of 1.03 years prior to diagnosis were identified earlier by PEB, at an average of 2.70 years. An algorithm based on repeated measurements of the 4MP improves sensitivity and results in an earlier detection of lung cancer compared to a single-threshold method. This study was supported by NIH Grant Nos. U01CA271888, U01CA194733, U01CA213285, NCI EDRN U01 CA200468, P30CA016672, and U24CA086368; the Cancer Prevention & Research Institute of Texas RP180505 and RP160693; the SPORE P50CA140388; the CCTS TR000371; and the generous philanthropic contributions to The University of Texas MD Anderson Cancer Center Moon Shots Program and the Lyda Hill Foundation.

Knowledge-map and research trends of circulating tumor cells in breast cancer: a scientometric analysis

Assessing circulating tumor cells (CTCs) in early-stage breast cancer patients can help identify relapse risk for timely interventions. Molecular analysis of CTCs can reveal vulnerabilities for personalized treatment options in metastatic breast cancer. This study aims to summarize CTCs in breast cancer research understanding and evaluate research trends. Extracted from the Web of Science Core Collection, publications on CTCs in breast cancer studies spanning from January 1, 2008, to December 21, 2023, were included. Co-authorships, references, and keywords were analyzed using Bibliometrix R packages and VOSviewer software. References and keywords burst detection were conducted with CiteSpace, and BICOMB was utilized to generate high-frequency keyword layouts. Biclustering analysis of the binary co-keyword matrix was performed using gCLUTO. 1747 articles focusing on CTCs in breast cancer were identified. The USA and the University of Texas MD Anderson Cancer Center demonstrated the highest productivity at the national and institutional levels, respectively. The journal “CANCERS” had the highest publication outputs on this subject. Pantel K emerged as the foremost author with the highest publication and co-citation counts. Analysis of co-keywords unveiled five prominent research areas concerning CTCs in breast cancer. The prognostic and predictive roles of CTCs in breast cancer have substantial implications for clinical practice. Nevertheless, precise assessment of CTCs, encompassing its quantities and attributes through advanced technologies, and its role in detecting minimal residual disease in breast cancer, continue to pose notable challenges. In conclusion, recent advancements and trends in CTCs research in breast cancer are examined through scientometric analysis in this study. The results provide valuable insights for the formulation of novel approaches in CTCs research, emphasizing the current research frontiers.

Abstract B130: Partnership in persistent poverty neighborhoods: The Acres Homes Cancer Prevention Collaboration

Abstract Introduction: Rising obesity rates significantly contribute to increases in many types of cancer. The link between obesity, socioeconomic status, and cancer risk is evident, particularly in persistent poverty areas. The Acres Homes Cancer Prevention Collaboration (Acres Homes CPC), part of the Persistent Poverty Initiative (PPI) of the National Cancer Institute, is a dynamic partnership led by the University of Texas MD Anderson Cancer Center. This community-academic partnership, centered on the Acres Homes neighborhood in Houston, TX, that is impacted by persistent poverty, utilizes community-engaged strategies and transdisciplinary research to mitigate obesity-related cancer risks. Methods: Through multiple community partnerships, the CPC aims to alleviate persistent poverty effects, support early-career researchers, and test nutrition and physical activity interventions for reducing obesity-related cancer risk. Results: The Acres Homes CPC funds two research projects: a trial of a physical activity program for cancer survivors and a cluster-randomized trial of food distribution and nutrition education for elementary school children and their parents. We have funded seven pilot studies on topics such as food security, culinary medicine, physical activity and mild cognitive impairment, and the physical and safety environment of neighborhoods. Three community advisors guide and support all activities, and information on the initiative is provided monthly to a community steering committee. The Acres Homes CPC also supports pre- and postdoctoral fellows interested in research promoting cancer prevention and control in persistent poverty communities. Conclusions: This initiative aims to reduce cancer risk and improve cancer outcomes in persistent poverty communities by bridging the gap between research and practical implementation through community-based participatory research and partnership with the community to address obesity. Citation Format: Karen Basen-Engquist, Ruth Rechis, Michael Mackert, Brad Love, Shreela Sharma, Sanjay Shete, Qian Lu, Shine Chang, Margaret Raber, Miranda Baum, Crystal Roberson, Lorna McNeill. Partnership in persistent poverty neighborhoods: The Acres Homes Cancer Prevention Collaboration [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B130.

Computed tomography radiomics-based cross-sectional detection of mandibular osteoradionecrosis in head and neck cancer survivors.

This study aims to identify radiomic features extracted from contrast-enhanced CT scans that differentiate osteoradionecrosis (ORN) from normal mandibular bone in patients with head and neck cancer (HNC) treated with radiotherapy (RT). Contrast-enhanced CT (CECT) images were collected for 150 patients (80% train, 20% test) with confirmed ORN diagnosis at The University of Texas MD Anderson Cancer Center between 2008 and 2018. Using PyRadiomics, radiomic features were extracted from manually segmented ORN regions and the corresponding automated control regions, the later defined as the contralateral healthy mandible region. A subset of pre-selected features was obtained based on correlation analysis (r > 0.95) and used to train a Random Forest (RF) classifier with Recursive Feature Elimination. Model explainability SHapley Additive exPlanations (SHAP) analysis was performed on the 20 most important features identified by the trained RF classifier. From a total of 1316 radiomic features extracted, 810 features were excluded due to high collinearity. From a set of 506 pre-selected radiomic features, the optimal subset resulting on the best discriminative accuracy of the RF classifier consisted of 67 features. The RF classifier was well calibrated (Log Loss 0.296, ECE 0.125) and achieved an accuracy of 88% and a ROC AUC of 0.96. The SHAP analysis revealed that higher values of Wavelet-LLH First-order Mean and Median were associated with ORN of the jaw (ORNJ). Conversely, higher Exponential GLDM Dependence Entropy and lower Square First-order Kurtosis were more characteristic of normal mandibular tissue. This study successfully developed a CECT-based radiomics model for differentiating ORNJ from healthy mandibular tissue in HNC patients after RT. Future work will focus on the detection of subclinical ORNJ regions to guide earlier interventions.

Medical Writing and Editing Internships: Preparing the Next Generation of Medical Communication Professionals

Conference Education Session Report Speakers Barbara Gastel, MD, MPH, ELS(H), Professor, Texas A&M University, College Station, TX Joan Affleck, MA, MBA, Associate Vice President, Head of Medical Writing, Merck & Co., Inc., Rahway, NJ Moderator Erica Goodoff, ELS(D), Senior Scientific Editor, The University of Texas MD Anderson Cancer Center, Houston, TX

Circulating Galectin-3: A Prognostic Biomarker in Hepatocellular Carcinoma

ABSTRACT Introduction Galectin-3 plays critical roles in the adhesion, proliferation, and differentiation of tumor cells. Recent data have suggested that galectin-3 plays a role in the development of hepatocellular carcinoma (HCC); however, its prognostic value has not been validated. The aim of our study was to evaluate the clinical and prognostic value of galectin-3 in patients with HCC. Methods We prospectively enrolled and collected clinicopathologic data and serum samples from 767 patients with HCC between 2001 and 2014 at The University of Texas MD Anderson Cancer Center. Two hundred patients without HCC were also enrolled and had data collected. The Kaplan-Meier method was used to estimate overall survival (OS) distributions. Results The median OS in this cohort was 14.2 months (95% CI, 12–16.1). At the time of analysis, the 1-year OS rate was 45% (95% CI, 0.4–0.51) among patients with high galectin-3 levels and 59% (95% CI, 0.54–0.63) among patients with low galectin-3 levels. OS was significantly inferior in patients with high galectin-3 levels than in patients with lower galectin-3 levels (median OS: 10.12 vs. 16.49 months; p = 0.0022). Additionally, the multivariate model showed a significant association between high galectin-3 level and poor OS (hazard ratio [HR] = 1.249; 95% CI, 1.005–1.554). Comparison between low (n = 464 patients) and high (n = 302 patients) galectin-3 levels showed that mean serum galectin-3 levels were significantly higher in patients with HCC who had hepatitis C virus (HCV) infection (p = 0.0001), higher Child-Pugh score (CPS) (p = 0.0009), and higher Cancer of the Liver Italian Program (CLIP) score (p = 0.0015). Conclusion Our study shows that serum galectin-3 level is a valid prognostic biomarker candidate.

Glycemic control in diabetic patients improved overall lung cancer survival across diverse populations.

The consequence of diabetes on lung cancer overall survival (OS) is debated. This retrospective study used 2 large lung cancer databases to assess comprehensively diabetes effects on lung cancer OS in diverse demographic populations, including health disparity. The University of Texas MD Anderson Cancer Center database (32 643 lung cancer patients with 11 973 patients with diabetes) was extracted from electronic health records (EHRs) using natural language processing (NLP). Associations were between diabetes and lung cancer prognostic features (age, sex, race, body mass index [BMI], insurance status, smoking, stage, and histopathology). Hemoglobin A1C (HgbA1c) and glucose levels assessed glycemic control. Validation was with a Louisiana cohort (17 768 lung cancer patients with 5402 patients with diabetes) enriched for health disparity cases. Kaplan-Meier analysis, log-rank test, multivariable Cox proportional hazard models, and survival tree analyses were employed. Lung cancer patients with diabetes exhibited marginally elevated OS or no statistically significant difference versus nondiabetic patients. When examining OS for 2 glycemic levels (HgbA1c > 7.0 or glucose > 154 mg/dL vs HgbA1c > 9.0 or glucose > 215 mg/dL), a statistically significant improvement in OS occurred in lung cancer patients with controlled versus uncontrolled glycemia (P < .0001). This improvement spanned sex, age, smoking status, insurance status, stage, race, BMI, histopathology, and therapy. Survival tree analysis revealed that obese and morbidly obese patients with controlled glycemia had higher lung cancer OS than comparison groups. These findings indicate a need for optimal glycemic control to improve lung cancer OS in diverse populations with diabetes.

Assessing Disease Control in Mismatch Repair-Proficient Colorectal Cancer With Peritoneal Metastases Treated With Immune Checkpoint Blockade-Based Combination Therapies

PURPOSE Metastatic colorectal adenocarcinoma (mCRC) with proficient mismatch repair (pMMR) is associated with poor response to cytotoxic chemotherapy in the refractory setting. Immunotherapy regimens using a combination of immune checkpoint blockade (ICB)–based combination therapies have shown promise, although few studies include patients with peritoneal metastases (PMs). This study sought to examine the disease control rate (DCR) and overall survival (OS) of patients treated with PM who were treated with ICB-containing regimens. METHODS Patients with pMMR metastatic colorectal cancer treated with ICB-based combination regimens after progression on first- and second-line therapy at The University of Texas MD Anderson Cancer Center from 2015 to 2022 were identified. Disease response within each metastatic site was determined. OS and DCR were calculated. RESULTS A total of 30 patients with PM, with or without other metastases, had a median follow-up on an ICB containing regimen of 8.5 months and a median follow-up until death or censoring of 13.3 months. The median OS was 16.7 (10.0-Not reported) months, and 18-month survival was 47%. Among patients treated for ≥6 months, DCR at 6 months at each metastatic site was 20% (2/10) for liver, 68% for peritoneum (13/19, P = .02 v liver), 50% for lung (5/10, P = .35 v liver), and 0% for retroperitoneal adenopathy (0/2, P = 1.00 v liver). CONCLUSIONS Among patients with mCRC, ICB-based combination regimens can provide disease control in the peritoneum in the majority of patients, and median OS compares favorably to standard-of-care therapy in the refractory setting. Patients with peritoneal disease should be included in future ICB trials since treatment options are otherwise limited.

Bibliometric analysis of global research in palliative care for cervical cancer.

The present study aims to conduct a comprehensive bibliometric analysis of global research in palliative care for cervical cancer, providing insights into publication trends, authorship patterns, influential journals, and thematic concentrations. A bibliometric analysis approach was employed using metadata extracted from Scopus spanning 2000-2023. The search utilized main terms related to cervical cancer and palliative care. Data analysis and visualization were performed using the Bibliometrix R Package's web app Biblioshiny and VOSviewer software. The study identified 2,492 publications on palliative care for cervical cancer, with a notable peak in 2021. The analysis revealed a diverse publication landscape, encompassing primarily articles. Citation analysis showed a staggering 63,994 citations. The most relevant journals were The Lancet Oncology, Gynecologic Oncology, and International Journal of Gynecological Cancer. The study also highlighted influential authors, institutions, and countries, with Harvard University, the University of Toronto, and the University of Texas MD Anderson Cancer Center leading in publications. The findings reflected a growing interest in palliative care for cervical cancer, marked by increasing publications over the years. However, the analysis indicated limited international collaborations, with research efforts concentrated in high-income countries. Thematic areas include surgery, palliative care, chemotherapy, radiotherapy, and quality of life. Thus, further collaborations and research in developing countries are needed. This bibliometric analysis showcased a comprehensive overview of the global research landscape on palliative care for cervical cancer. The study identified trends, key contributors, and thematic concentrations, offering valuable insights for future research directions and enhancing palliative care services. Addressing the identified gaps, fostering international collaborations, and directing research efforts toward developing countries can contribute to the advancement of palliative care for cervical cancer globally.

Global research trends in the treatment of squamous cell carcinoma over the past decade: A bibliometric analysis

ObjectiveThis study aims to identify research trends and hot spots in the treatment of Squamous Cell Carcinoma (SCC) over the past decade using bibliometric analysis. MethodsData were extracted from the Web of Science Core Collection, including Science Citation Index Expanded (SCI-Expanded), Social Sciences Citation Index (SSCI), and Emerging Sources Citation Index (ESCI). The data underwent manual cleaning to remove inaccuracies and irrelevancies, followed by transformation into an analyzable format via the VOSviewer software. This tool facilitated the visualization of co-occurrence networks and keyword maps, highlighting the relationships and the prominence of research themes. ResultsA total of 46448 authors from 7374 institutions across 108 countries contributed to the literature, reflecting a broad international effort. The study documented a consistent increase in SCC-related publications up to 2020, with some variability in subsequent years. Notably, the United States, Germany, China, the United Kingdom, and France were predominant in this research area. The University of Texas MD Anderson Cancer Center and the University of Pittsburgh were leading contributors in terms of publication volume and citation impact. Key journals included ‘Oral Oncology’ and ‘Clinical Cancer Research’, which were central to the dissemination of high-impact research. Our keyword analysis identified three major research clusters focused on molecular mechanisms, clinical treatment strategies, and emerging interests in immunotherapeutic approaches. ConclusionsThe extensive collaboration and the increasing publication trend underscore the growing global commitment to advancing SCC treatment. The high level of engagement from top institutions and the concentration of research in influential journals reflect the field's dynamic evolution towards innovative and effective treatment modalities. This study provides a valuable overview for researchers, guiding future studies towards areas of high impact and emerging trends in SCC treatment. The findings advocate for enhanced focus on personalized medicine and combination therapies, which are poised to improve outcomes for SCC patients.

Bibliometric analysis and visualisation of research hotspots and frontiers on omics in osteosarcoma

Background/objectiveOmics technology has become a widely applied biological science that can be used to study the etiology, pathogenesis, and treatment of osteosarcoma(OS). Bibliometric analysis is still blank in this field.This study aimed to access the trends and hotspots of omics in OS research through the bibliometric analysis method.MethodsRelevant articles and reviews from 1999 to 2023 were retrieved from the Web of Science Core Collection. The data were processed with CiteSpace, and some graphs were generated with Graphpad, VOSviewer, Scimago Graphica, Bibliometrix and R Studio.ResultsA total of 1581 papers were included. China (569, 36.0%) and the United States (523, 33.1%) took the dominant position in the number of published papers, and the links between countries most frequently occurred between North America and East Asia, and between Australia and Europe. Top institutions with the highest number of publications were almost located in the United States, with The University of Texas MD Anderson Cancer Center contributing the most (44, 2.78%). Among the researchers in this field, Cleton-Jansen AM was the author with the highest number of articles in the field (20, 1.27%). According to the keyword cluster analysis, most studies focused on the “comparative genomic hybridization” before 2012. The latest surge words “tumor microenvironment” and “immune infiltration” in the keyword heatmap indicate future research directions.ConclusionOur study provided the current status of the omics research in OS on a global level and the hottest directions. The field of omics in OS was developing rapidly, and the main focuses of research were revealing the characteristics of tumor microenvironment of OS and how to activate the immune system to fight cancer cells. Research on the immune microenvironment and its relationship with genetic aberrations of OS will be a priority in the future.

Mandibular dose-volume predicts time-to-osteoradionecrosis in an actuarial normal-tissue complication probability (NTCP) model: External validation of right-censored clinico-dosimetric and competing risk application across international multi-institutional observational cohorts and online graphical user interface clinical support tool assessment.

Existing studies on osteoradionecrosis of the jaw (ORNJ) have primarily used cross-sectional data, assessing risk factors at a single time point. Determining the time-to-event profile of ORNJ has important implications to monitor oral health in head and neck cancer (HNC) long-term survivors. Demographic, clinical and dosimetric data were retrospectively obtained for a clinical observational cohort of 1129 patients with HNC treated with radiotherapy (RT) at The University of Texas MD Anderson Cancer Center. ORNJ was diagnosed in 198 patients (18%). A multivariable logistic regression analysis with forward stepwise variable selection identified significant predictors for ORNJ. These predictors were then used to train a Weibull Accelerated Failure Time (AFT) model, which was externally validated using an independent cohort of 265 patients (92 ORNJ cases and 173 controls) treated at Guy's and St. Thomas' Hospitals. Our model identified that each unit increase in D25% is significantly associated with a 12% shorter time to ORNJ (Adjusted Time Ratio [ATR] 0·88, p<0·005); pre-RT dental extractions was associated to a 27% faster (ATR 0·73, p=0·13) onset of ORNJ; male patients experienced a 38% shorter time to ORNJ (ATR 0·62, p = 0·11). The model demonstrated strong internal calibration (integrated Brier score of 0·133, D-calibration p-value 0.998) and optimal discrimination at 72 months (Harrell's C-index of 0·72). The model also showed good generalization to the independent cohort, despite a slight drop in performance. This study is the first to demonstrate a direct relationship between radiation dose and the time to ORNJ onset, providing a novel characterization of the impact of delivered dose not only on the probability of a late effect (ORNJ), but the conditional risk during survivorship. This work was supported by various funding sources including NIH, NIDCR, NCI, NAPT, NASA, BCM, Affirmed Pharma, CRUK, KWF Dutch Cancer Society, NWO ZonMw, and the Apache Corporation.