Cancer Medicine最新文献

Background: Cutaneous melanoma is a rising global health concern and identifying modifiable or associated risk factors remains essential for improving prognostic stratification. Hypothyroidism, affecting approximately 5.1% of the general population in Germany, has been associated with various malignancies. This study investigates the prevalence and potential prognostic implications of hypothyroidism in melanoma patients.

Methods: We conducted a retrospective single-centre study including 1553 patients with cutaneous melanoma (AJCC stages I-III). Patients were stratified based on thyroid function into hypothyroid and euthyroid groups. Data were collected via clinical records and standardized patient questionnaires.

Results: Hypothyroidism was documented in 234 patients (15.1%), significantly higher than the national prevalence (5.1%, p < 0.001). Tumor site differed significantly between groups, with hypothyroid patients more frequently exhibiting melanomas on the lower extremities (p < 0.001). These patients also showed a non-significant trend toward lower Breslow thickness (p = 0.09) and a significantly reduced number of metastatic lymph nodes (p = 0.009).

Conclusions: Our findings suggest that hypothyroidism is markedly more prevalent among patients with cutaneous melanoma and may be associated with clinical features linked to improved prognosis. These observations warrant further investigation to clarify whether hypothyroidism itself, or its underlying immunologic and hormonal milieu, plays a protective role in melanoma progression.

Background: Although the impact of increased time to treatment initiation (TTI) on outcomes for patients with oropharyngeal squamous cell carcinoma (OPSCC) has been well-studied, a deeper understanding of the mechanisms underlying delay in patients with human papillomavirus (HPV)-negative OPSCC is lacking in the current literature.

Objective: To assess differences in sociodemographic factors and treatment timelines between patients with HPV-negative OPSCC with shorter versus. longer TTI.

Methods: Patients treated for HPV-negative OPSCC at a single academic institution between 2013 and 2023 were retrospectively identified via chart review and dichotomized by the cohort median TTI (53.5 days; defined as the time from biopsy to first treatment initiation). Clinical timelines between delayed and nondelayed patients were compared using descriptive statistics and Mann-Whitney U testing. Independent predictors of delayed TTI (> 53.5 days) were evaluated using multivariate logistic regression modeling, with adjusted odds ratios (aORs) and 95% confidence intervals reported.

Results: Seventy-six patients were identified. On multivariable analysis, male sex (aOR 3.28; 95% CI 1.02-10.49), unmarried status (aOR 5.96; 95% CI 1.36-26.07), primary chemoradiation versus surgery (aOR 0.25; 95% CI 0.07-0.85), and biopsy available before arrival (aOR 4.08; 95% CI 1.32-17.36) were independently and significantly (p< 0.05) associated with delayed treatment initiation. Treatment timeline analysis revealed that both the interval from biopsy to referral and the interval from PET scan to treatment initiation differed significantly between delayed and nondelayed patients (p< 0.05).

Conclusion: Primary nonsurgical treatment and lack of social support were found to be independently associated with treatment delay in patients with HPV-negative OPSCC. These findings highlight opportunities for improving the care of HPV-negative OPSCC at the specialty level.

Background: Exercise mitigates chemotherapy-related cardiotoxicity, but implementing exercise interventions during chemotherapy treatment can be challenging. Understanding the patient perspective can help refine exercise programs and facilitate successful implementation of future interventions.

Purpose: To utilize qualitative data to optimize adherence and retention for a future randomized clinical trial involving a tailored physical activity (PA) intervention among breast cancer and lymphoma patients receiving potentially cardiotoxic chemotherapy.

Methods: Eighteen breast cancer and lymphoma patients receiving potentially cardiotoxic chemotherapy who enrolled in a PA intervention completed semi-structured interviews. Interviews focused on reasons for enrollment or dropout, perceptions of study personnel, experiences within the study interventions, and barriers to intervention adherence. Interviews were audio recorded. Key points and potential themes were identified using an integrative synthesis of the data.

Results: Participants were on average 53 years (SD = 15) old, were 50% female (n = 9), predominantly identified as White (n = 15, 83%), and were mostly non-Hodgkin Lymphoma patients (n = 11, 61%). The main reasons for enrollment were altruism and provider recommendation. Participants stated they completed the study because of intrinsic motivation, ease of participation, and positive study experiences. Participants reported favorable perceptions of the study interventions and study staff. Barriers to adherence included symptom burden and lack of motivation.

Conclusions: Messages to enhance altruism and collaboration with providers may be important recruitment tools. Developing positive study-staff relationships and delivering tailored, flexible interventions may enhance study adherence and retention. Ultimately, these strategies contribute to the successful implementation of cancer exercise trials.

Trials registration: NCT01719562.

Background: Conventional treatment strategies and immunotherapy yield low response rates in head and neck squamous cell carcinoma (HNSCC). This study aimed to explore the potential of immunosuppressive receptor leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) for developing effective immunotherapies for HNSCC.

Methods: Clinical data collection and analysis were determined using Tumor Immunity Estimation Resource Database (TIMER) and Cancer Treatment Response gene signature DataBase (CTR-DB). Immunohistochemistry was used to detect protein level in fresh breast cancer tissues. RNA sequencing was employed to screen the downstream signaling pathway in WBP2-overexpressed cells. Tumor xenograft model and Flow Cytometry were performed to monitor tumor growth and cell apoptosis, respectively.

Results: In this study, high expression of LILRB1 in HNSCC tissues was observed compared to normal tissues. HNSCC patients with high LILRB1 expression exhibited a better prognosis, which was influenced by tumor mutation burden. Functional network analysis revealed a positive association between LILRB1 and chemokine signaling pathways. Copy number variation of LILRB1 was positively correlated with the infiltration of CD8+ T cells and M1 macrophages. The prognostic effect of LILRB1 depends on CD8+ T-cell abundance, especially in HNSCC with a low neoantigen load. High LILRB1 expression was associated with a higher immune score, indicating favorable outcomes in HNSCC patients receiving immunotherapy. Notably, LILRB1 was specifically expressed in SPP1-ACP5+ macrophages; in these cells, high LILRB1 might reduce the proportion of cancer cells via the SPP1-CD44 axis, and subsequently regulate CD8+ T cell enrichment through the C-X-C motif chemokine 13 (CXCL13)-CXCR5 axis.

Conclusion: Collectively, high LILRB1 expression in HNSCC was accompanied by the infiltration of various immune effector cells. LILRB1 may shape the tumor microenvironment of HNSCC, mediating the interactions between cancer cells and macrophages, as well as between cancer cells and CD8+ T cells, via the SPP1-CD44 and CXCL13-CXCR5 axes. Our findings illustrate that LILRB1 serves as a prognostic-related biomarker associated with immune infiltration in HNSCC.

Purpose: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive and prevalent cancers in China, a deeper understanding at the molecular level is the cornerstone for advancing precision oncology in ESCC. This study aims to investigate the role of CAPZA1 in ESCC progression. Based on our previous whole genome sequencing (WGS) and whole exome sequencing (WES) data indicating frequent copy number loss of CAPZA1 in ESCC, as well as the presence of a specific single nucleotide polymorphism (SNP, rs373245753 T>G) in its 3'UTR via the dbSNP database (https://www.ncbi.nlm.nih.gov/snp/), we sought to determine the functional and mechanistic impact of CAPZA1 genotypes on ESCC cell behavior.

Materials and methods: We identified the SNP rs373245753 within the 3'UTR of the CAPZA1 gene via the dbSNP database. To investigate its functional impact, we established stable ESCC cell lines overexpressing either the CAPZA1[T] or CAPZA1[G] variant and evaluated their migration and invasion capabilities using transwell assays. Subsequently, we performed subcutaneous xenograft experiments by injecting these cells into the lower limbs of mice to monitor tumor growth in vivo. Furthermore, siRNAs were used to efficiently reduce mRNA expression of CAPZA1, then xCELLigence Real-Time Cell Analyzer (RTCA)-MP system and colony formation assay were employed to detect cell proliferation ability. To elucidate the underlying molecular mechanism, we employed biotin-RNA pulldown assays coupled with mass spectrometry, along with RNA immunoprecipitation (RIP) assays, to identify RNA-binding proteins interacting with the CAPZA1 mRNA variants. Finally, we assessed the impact of these proteins on CAPZA1 mRNA stability through mRNA decay assays.

Results: According to the dbSNP database, we identified the SNP rs373245753 within the 3'UTR of the CAPZA1 gene. Overexpression of CAPZA1[T] significantly inhibited ESCC cell migration and invasion, while the CAPZA1[G] variant attenuated this suppression both in vivo and in vitro. Biotin-RNA pulldown combined with mass spectrometry and RIP assays showed that CAPZA1[T] mRNA binds to hnRNP K and PTBP1, enhancing its stability and tumor-suppressive function. In contrast, CAPZA1[G] mRNA preferentially bound UPF1, leading to accelerated mRNA decay and loss of tumor suppression.

Conclusion: CAPZA1 acts as a tumor suppressor in ESCC, with its function dependent on genotype. The CAPZA1[T] variant binds hnRNP K and PTBP1 to stabilize its mRNA and inhibit tumor aggressiveness, whereas the CAPZA1[G] allele promotes UPF1-mediated mRNA decay and diminishes this protective effect. These findings reveal a novel post-transcriptional regulatory mechanism underlying ESCC progression and highlight CAPZA1 genotype as a potential prognostic marker and therapeutic target.

Background: Previous studies have indicated that diffuse large B-cell lymphoma (DLBCL) patients with a low baseline skeletal muscle (SM) area are more susceptible to severe toxicity during chemotherapy. However, the predictive role of baseline body composition in determining toxicity risk during the initial frontline treatment remains unexplored. This study aims to identify reliable, non-invasive biomarkers and validate findings using follow-up CT scans after four cycles of chemotherapy.

Methods: We retrospectively included DLBCL patients who received four cycles of R-CHOP treatment between January 2015 and January 2024, with pre-treatment abdominal CT scans. We measured the volume, area, and density of SM, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) to assess their predictive potential for chemotherapy toxicity. Subgroup analyses examined longitudinal changes in body composition, and a logistic regression model identified effective imaging biomarkers associated with grade 3/4 toxicity.

Results: Among the 179 DLBCL patients (mean age 56.96 ± 13.49 years), 46.9% experienced grade 3/4 toxicity. Lower baseline SM volume and density significantly increased the risk of toxicity, particularly in overweight or obese patients (p < 0.05). ROC analysis identified SM volume as the best predictor, with a cutoff of 2093.71 cm³; patients below this threshold had a 3.34 times higher risk (p = 0.001). A decrease in SM volume was associated with higher risks of hematological toxicity (p = 0.022) and neutropenic fever (p = 0.021).

Conclusion: Lower baseline SM volume and its reductions during treatment are associated with an increased risk of grade 3/4 toxicity, particularly in overweight or obese patients. Body composition measurements serve as effective imaging biomarkers.

Purpose: Osteosarcoma is the most common primary bone tumor in childhood and adolescence. Many patients face long-term impairments in their mobility and function after treatment, leading to a decrease in their quality of life. Exercise has been shown to improve functional recovery and improve quality of life in patients with cancer, though data specific to children with osteosarcoma are sparse. Exercise has also been shown to be feasible in patients undergoing chemotherapy, with numerous potential benefits to health and quality of life. To design the most effective exercise interventions for children and adolescents with osteosarcoma, we must first understand the activity patterns in this population throughout the treatment and survivorship continuum.

Methods: In this study, we provided wearable activity trackers to osteosarcoma patients to evaluate physical activity patterns. Inclusion criteria allowed for any age, gender, or stage of treatment (including after treatment completion).

Results: Twenty-six patients had valid data defined as 3 or more days with more than 10 h of continuous heart rate data. The average steps per day across all treatment stages including post treatment was 3184 ± SD 2552.74, range 0-27,828 steps on treatment days and 4884 ± 2447.30, range 0-22,500 steps on off treatment days. Values for specific treatment periods (neoadjuvant, adjuvant, relapse, off therapy) are presented. Though activity patterns varied widely between patients, all patients except one were below recommended values for daily step counts until after therapy was complete.

Conclusion: Our results suggest that tailoring an exercise program to encourage activity on days when patients receive antineoplastic therapy, and to have the more intensive exercise days well after antineoplastic therapy, may be a good approach. Further research is needed to define interventions to improve physical activity in this population.

Introduction: In low- and middle-income countries (LMICs) such as Tanzania, non-adherence and treatment abandonment are major factors contributing to low childhood cancer survival rates. Providing guardians with reminders and information via an SMS intervention may increase adherence and reduce treatment abandonment. The purpose of the GuardiansCan project is to reduce guardians' abandonment of children's maintenance therapy for acute lymphoblastic lymphoma (ALL) in Tanzania, thereby increasing ALL survival rates in the country by developing and evaluating an SMS intervention. We report initial results from phase one of a mixed-method examination of public contribution activities in the GuardiansCan project. We aimed to: recruit guardians of children treated for ALL to a Guardian Advisory Board (GAB) to contribute to the design and conduct of Study II within the GuardiansCan project (Study II) and the wider GuardiansCan project; and examine the acceptability, feasibility, and impact of GAB members' contribution from the perspective of GAB members and public contribution coordinators (coordinators).

Methods: We adopted a convergent parallel mixed-methods design, using impact logs and semi-structured interviews, with data integrated at the point of analysis. During four workshops, GAB members provided suggestions and recommendations, which were recorded in impact logs. GAB members and coordinators were interviewed about the acceptability, feasibility, and impact of GAB members' contributions.

Results: Nine guardians were recruited. GAB members made 63 suggestions and recommendations, of which 50 (79%) were implemented. Semi-structured interviews resulted in seven categories: Meaning and value, Motivation and willingness to volunteer, Suggestions and areas for improvement, Barriers and challenges, Facilitators, Personal impact, and Research impact.

Conclusion: Findings suggest GAB members' contribution was acceptable and feasible, and had an impact on both the research and GAB members themselves. Findings can inform how to meaningfully involve public contributors in LMICs.

Introduction: Fewer than 50% of Native American (NA) women screen for both cervical and colorectal (CRC) cancer. We aim to explore the perspectives of NAs around cervical and colorectal cancer home-based self-screening options.

Methods: The NA community provided review and approval for this cross-sectional survey on cancers in general, and specifically on cervical and colorectal cancer screening. We invited screen-eligible Native American women, aged 45-65 years, who attended the Lakota Nation Invitational tournament in December 2023, to complete the survey.

Results: One hundred women, with a mean age of 54.1 (SD 6.3), completed the survey. Respondents reported visiting their doctor once a year, rarely (10%), with 66% experiencing a poor experience accessing healthcare-only 16% self-reported screening for both cervical and colorectal cancers within the last 5 years. If the participant could screen for both cervical and CRC cancer at home, 83.0% said they would be willing to do both, compared to 9% who would do neither at home. The doctor's recommendation for how to screen for cervical and CRC cancer was the most important factor in screening decision-making. The other two very important reasons were how easy or convenient the screening is, how comfortable I am with the screening process/what happens to me during the test.

Conclusions: With the recommendation of their doctors, and convenience and comfort being important, Native American women are enthusiastic to participate in home-based cervical and colorectal cancer screening. While the home-based CRC screening has been available for many years, with minimal effect on screening uptake, the advent of self-sampling for primary HPV testing for cervical cancer appears to create interest for both tests at home. These options may increase both cancer screening rates and access to care in this underserved population.

Background: ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) is a rare subtype of peripheral T-cell lymphoma with traditionally favorable prognosis. The introduction of brentuximab vedotin (BV) has significantly impacted treatment outcomes, but the long-term survival trends and predictive factors for this population remain underexplored.

Methods: A total of 1548 patients diagnosed with ALK+ ALCL between 2004 and 2017 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized into two eras: pre-BV (2004-2010, n = 795) and post-BV (2011-2017, n = 753). Overall survival (OS) was compared between eras. A random survival forest (RSF) model was constructed to identify prognostic factors and stratify survival risk in the post-BV cohort.

Results: OS significantly improved in the post-BV era (HR = 0.68, 95% CI: 0.58-0.81, p < 0.001), with the 5-year OS increasing from 59.3% to 72.3%. The RSF model identified age, Ann Arbor stage, primary site, B symptoms, and radiotherapy as key prognostic factors, showing good discrimination with C-indices of 0.775 (training cohort) and 0.728 (testing cohort). Notably, radiotherapy was found to be a protective factor. The model effectively stratified patients into high-risk (5-year OS: 49.3%) and low-risk (86.0%) groups.

Conclusion: The introduction of BV has significantly improved real-world survival in ALK+ ALCL. The RSF model enables individualized risk stratification and may support future precision treatment strategies.