Nasopharyngeal carcinomas (NPC) are malignancies that have seen growing burdens with human papilloma virus (HPV) infection. This investigation aims to characterize social determinant factor of health (SDoH) differences across HPV-differentiated NPC across the USA. NPC-patients with confirmed-HPV status between 2010 and 2018 from the Surveillance-Epidemiology-End Results (SEER) database were analyzed by cox-proportional and logistic regressions of age, sex, race-ethnicity, census-level rurality-urbanicity, and census-level Yost-Socioeconomic Status (SES)-Index measures to assess mortality, staging, and delayed-treatment differences. Among 820-HPV( -) and 402-HPV(+) NPCs, both NPC-cohorts displayed reduced overall mortality risk with younger age (HR 0.56, 95% CI 0.38-0.81; HR 0.57, 0.45-0.73) and higher risk with male sex (HR 1.71, 95% CI 1.11-2.64; HR 1.42, 95% CI 1.07-1.87). For HPV(-) only, Hispanic (HR 0.51, 95% CI 0.32-0.82) and Asian ethnicities (HR 0.44, 95% CI 0.33-0.58) reduced overall mortality risk, while low Yost-SES-Index increased it (HR 1.44, 1.14-1.87). For HPV( -) only, delayed treatment occurred with lower Yost-SES-Index (OR 1.97, 95% CI 1.16-3.42). Using the Yost-SES-Index and other individual/census-level SDoH, multilevel SDoH-analyses of HPV-differentiated NPC-patients display vast prognostic and treatment differences based on HPV-status. These present specific targets to prospectively and strategically address drivers of disparity with limited public health resources.

RNA editing by adenosine deaminase acting on RNA (ADAR) enzymes plays a role in cancer progression. However, its clinical significance in metastatic colorectal cancer (CRC) remains unclear. This study aimed to evaluate whether ADAR1 expression predicts prognosis and treatment response in colorectal cancer (CRC) with synchronous liver metastasis. This study included 40 patients with stage IV CRC and synchronous liver metastases. ADAR1 expression in tumor tissues was evaluated using immunohistochemistry. Expression levels were quantified using the immunoreactive score, and associations with clinicopathological features, overall survival (OS), and chemotherapy response were examined. High ADAR1 expression was significantly associated with multiple liver metastases (P = 0.0206), lymph node metastasis (P = 0.0241), and reduced response to chemotherapy (P = 0.0224). Significantly shorter OS was observed in patients with high ADAR1 expression in the nucleus (P = 0.0458). ADAR1 expression was an independent prognostic factor comparable to the presence of extrahepatic metastases. Low ADAR1 expression was correlated with a higher likelihood of achieving a response to chemotherapy. ADAR1 expression can reflect tumor aggressiveness and chemotherapy resistance in patients with CRC and synchronous liver metastasis. ADAR1 has considerable potential as a dual-purpose biomarker for stratifying patients based on prognosis and optimizing treatment intensity.

Colorectal cancer is one of the common malignant tumors nowadays, with the highest mortality rate among cancers, and most patients have metastasis when diagnosed. Exosomes contain bioactive molecules such as RNA, which can participate in signal transduction between cells. tRF is a new type of non-coding small RNA, which plays an important role in the progression of cancer. The purpose of this study is to explore the value of exosomal tRF as a biological diagnostic marker for colorectal cancer. Through the use of transmission electron microscopy (TEM), qNano, and western blot, exosomes obtained from the serum of both healthy people and patients with colorectal cancer were characterized; the expression of tRNA-Gly-5-0007 was validated by real-time quantitative PCR (qRT-PCR) in the exosome of 172 colorectal cancer patients and 164 healthy people. The diagnostic efficacy of tsRNA-Gly-5-0007 as a diagnostic marker for colorectal cancer was evaluated by receiver operating characteristic curve (ROC) analysis. We further conducted a preliminary verification of how tsRNA-Gly-5-0007 participates in the malignant phenotype of tumors through transwell experiments and cell adhesion experiments. The TCGA database shows that tsRNA-Gly-5-0007 is an RNA fragment derived from tsRNA-Gly-CCC-2-1. The expression of tsRNA-Gly-CCC-2-1 is down-regulated in colorectal cancer tissues and may be involved in Wnt, mTOR and other signaling pathways. tsRNA-Gly-5-0007 can inhibit the adhesion and motor capacity of colorectal cancer cells. Compared with healthy people, the expression of exosomal tsRNA-Gly-5-0007 was significantly down-regulated in patients with colorectal cancer, especially in patients with early colorectal cancer. The diagnostic efficacy of exosomal tsRNA-Gly-5-0007 for the diagnosis of colorectal cancer was 0.7812, and the diagnostic efficacy for the diagnosis of early colorectal cancer was 0.7726. tsRNA-Gly-5-0007 may affect the adhesion and motor capacity of colorectal cancer cells through Wnt signaling pathway, and then participate in the malignant process of colorectal cancer cells. Moreover, the expression of exosomal tsRNA-Gly-5-0007 is down-regulated in colorectal cancer patients and can be used as a promising biomarker for the biological diagnosis of colorectal cancer.

Breast cancer is increasingly prevalent among older adults, who are likely to have numerous comorbidities and unique psychosocial challenges.

The aim of this study was to measure the prevalence of psychosocial factors in a cohort of older women diagnosed with early-stage operable breast cancer and the influence these factors may have on treatment decisions.

As part of a prospective study in three UK centres, 199 patients with a new diagnosis of early-stage operable primary breast cancer, aged ≥ 70 years (mean 77, range 68-93) were recruited. A cancer-specific Comprehensive Geriatric Assessment (CGA) was conducted within 6 weeks of diagnosis. Association between treatment decision and psychosocial aspects (as measured by the 'psychosocial support', 'social activity' and 'social support' domains) of the CGA was determined. Treatment decision was not guided by this study and was determined usual conventional methods as per the breast multi-disciplinary team.

Scores for 'psychosocial support' averaged 82.1/102, 'social activity' averaged 13.5/24, and 'social support' averaged 43.3/72; with a higher score indicating a more positive outcome. There was no association between total scores in these domains and the type of treatment received. A lower score in three individual questions was associated with a higher likelihood of non-surgical treatment.

While no direct link emerged between overall psychosocial scores and treatment decisions using CGA, specific sub-questions displayed associations with non-surgical treatment. This study is the only one of its kind to our knowledge. This may have implications for the design of a pre-CGA screening tool.

Despite its routine use to monitor patients with lung cancer (LC), real-world evaluations of the impact of computed tomography (CT) surveillance on overall survival (OS) have been inconsistent. A major confounder is the absence of imaging indications because patients undergo CT scans for purposes beyond surveillance, like symptom evaluations (eg, cough) linked to poor survival. We propose a novel natural language processing model to predict CT imaging indications (surveillance v others).

We used electronic health records of 585 long-term LC survivors (≥5 years) at Stanford, followed for up to 22 years. Their 3,362 post-5-year CT reports (including 1,672 manually annotated) were used for modeling by integrating structured variables (eg, CT intervals) with key-phrase analysis of radiology reports. Naïve analysis compared OS in patients with CT for any indications (including symptoms) versus those without post-5-year CT, as in previous studies. Using model-predicted indications, we conducted exploratory analyses to compare OS between those with post-5-year surveillance CT and those without.

The model showed high discrimination (AUC, 0.86), with key predictors including a longer interval (≥6-month) from the previous CT (odds ratios [OR], 5.50; P < .001) and surveillance-related key phrases (OR, 1.37; P = .03). Propensity-adjusted survival analysis indicated better OS for patients with any post-5-year surveillance CT versus those without (adjusted hazard ratio, 0.60; P = .016). By contrast, no significant survival difference was found (P = .53) between patients with any CT versus those without post-5-year CT.

Our model abstracted CT indications from real-world data with high discrimination. Exploratory analyses revealed the obscured imaging-OS association when considering indications, highlighting the model's potential for future real-world studies.

Gastrointestinal stromal tumor (GIST) resistance to imatinib and other tyrosine kinase inhibitors poses an ongoing clinical challenge. We investigated molecularly matched combination therapies for treatment-refractory GIST, including drugs not previously combined in human studies.

Patients of all ages with unresectable and/or metastatic GIST treated with combination therapies were included (February 13, 2015-December 31, 2022). These patients were discussed at molecular tumor board and enrolled in the prospective Investigation of Profile-Related Evidence Determining Individualized Cancer Therapy (I-PREDICT) study (ClinicalTrials.gov identifier: NCT02534675). Patient demographics, tumor next-generation sequencing (NGS), treatment responses, and survival outcomes were retrospectively analyzed.

Six (1.6%) patients met the inclusion criteria. The median age at diagnosis was 59.5 years with the majority (4/6) of patients being male. NGS revealed median of six deleterious genomic alterations per patient excluding variants of unknown significance. Five (5/6) patients had KIT-mutant GIST, and one patient had BRAF^V600E-mutant GIST. Two thirds of tumors had CDKN2A/B loss. Patients received median of 1 (range, 1-3) customized combination therapy consisting of median of 2 (range, 2-3) drugs targeting median of 2 (range, 2-4) genomic alterations. One patient experienced a treatment-related grade ≥3 adverse event (hypertension). For all patients, the best response by RECIST v1.1 was stable disease (SD). Combination therapies led to SD ≥6 months (range, 6.2-11.3 months) in four (4/6) patients compared with none in the immediate previous single-agent targeted therapies (SD range, 1.5-5.4 months). Most (5/6) patients had at least 60% prolongation of their progression-free survival compared with their immediate previous single-agent targeted therapy.

Our results demonstrate that a multitargeted, biomarker-matched combination approach can be safely administered to obtain disease control. Tailored combination therapies for advanced GIST with multiple genomic alterations warrant further investigation.

Despite initially responding to first-line treatment, many patients with non-Hodgkin's lymphoma (NHL) eventually relapse or are refractory. These patients are empirically subjected to salvage therapies that may not be efficacious. We had previously presented feasibility evidence of an ex vivo functional precision medicine (FPM) platform, quadratic phenotypic optimization platform (QPOP), being potentially useful in identifying alternative therapeutic options for patients with relapsed/refractory (R/R)-NHL. We now present an analysis of the completed prospective study, with clinical concordance and benefit of QPOP in predicting treatment responses of patients with R/R-NHL.

One hundred seventeen patients with R/R B-cell NHL (B-NHL) or natural killer or T-cell NHL (NK/T-NHL) were recruited for QPOP testing. Isolated tumor cells were incubated for 48 hours with drug combinations determined by an orthogonal array composite design. QPOP reports with patient-specific optimal drug therapies were generated. Patients were given off-label treatments according to the clinician's decision. Patient characteristics and responses to treatments after QPOP testing were recorded.

Within 126 QPOP cases, 105 (52 B-NHL and 53 NK/T-NHL) were evaluable. QPOP-suggested drug responses were concordant with actual patient outcome, with an overall test accuracy of 74.5%. An overall response rate of 59% was achieved in those prescribed off-label QPOP-guided combinations. In all, 59.3% of QPOP-guided patients had improved response durations compared with their previous treatment. Compared with those who received salvage therapy, QPOP-guided patients also had longer progression-free survival 2 years after treatment.

There is increasing evidence that genetic factors are not sole determinants of patient drug response and FPM approaches may improve cancer treatment guidance. This study further confirms that advancements in ex vivo combinatorial drug screening platforms like QPOP could complement existing genomic methods in identifying effective treatment options for patients with cancer, especially in R/R cases.

Acute leukemia is a group of hematologic malignancies categorized according to the immature cells that proliferate and replace the normal bone marrow. Flow cytometry has emerged as a cornerstone in the diagnosis of hematologic malignancies. Staged analysis with a screening tube containing specific lineage markers determines the need for subsequent testing if there is an abnormal population (blasts). The specific lineage panels to be analyzed are determined depending on the positive markers in the screening tube. This study aimed to determine the agreement of diagnosis using the acute leukemia screening tube (ALST) and the lineage-specific panel.

This was an analytical cross-sectional study performed at the Aga Khan University Hospital, Nairobi. It included 256 cases diagnosed as acute leukemia. The diagnosis after the screening tube was compared with the final diagnosis from the lineage-specific panels, and Cohen's Kappa was used to determine the level of agreement.

Of the 256 cases, the overall agreement was 94%, with 14 cases being discordant. Myeloperoxidase interpretation in the screening tube accounted for 64% (9 of 14) of the discrepant results.

The study demonstrated that the ALST is almost as good as lineage-specific panels in the diagnosis and classification of acute leukemias. The screening tube can be an added diagnostic tool to complement morphology in resource-limited centers with the capacity to interpret flow cytometry analysis.

We aimed to assess whether lung cancer (LC) screening with low-dose computed tomography (LDCT) is cost effective in a high-risk population (current or former smokers-who stopped smoking within <15 years-age 50-80 years, with a smoking history of at least 20 pack-years) in the Brazilian public health setting.

To estimate the size of the population eligible for screening, we used Brazilian 2020 census data and information provided by the nationwide surveillance system of risk factors for chronic diseases. For comparison, we used a nonscreened population of LC cases from the São Paulo state registry. We characterized patient journeys and estimated direct and indirect costs using the nationwide public health system database, DATASUS, and expert opinion from an ad hoc panel. We used Markov models for economic evaluations that considered treatment costs (in Brazilian currency, R$) and outcomes.

Adopting an LC screening strategy with LDCT in this high-risk population would be associated with an incremental cost-effectiveness ratio (ICER) of R$ 133,327 per quality-adjusted life year. For the life year outcome, the ICER was R$ 9,579 per life year gained. For both outcomes, the values were below the cost-effectiveness threshold considered (three times the per-capita gross domestic product, which corresponds to R$ 143,406.06 or $24,735.99 US dollars).

Our study confirms that implementing LC screening with LDCT in a high-risk population is cost effective in the Brazilian public health system.

Buccal mucosa cancer (BMC), the most prevalent oral cancer (OC) site, is a multifactorial disease. With relatively high prevalence of periodontal diseases because of poor oral hygiene practices, oral health indicators remain an area of exploration in the Indian context for its association with BMC.

A total of 1,673 histologically confirmed cases and 1,601 frequency-matched controls from a hospital-based, multicenter case-control study was analyzed for the risk of BMC because of the oral hygiene indicators-denture use, number of decayed, missing, and filled teeth, and the Decayed, Missing, Filled Teeth (DMFT) score. Logistic regression models, adjusted for potential confounders like age, sex, rural-urban status, education, and tobacco and alcohol use (duration and frequency), were used to estimate odds ratios (ORs) and 95% CI. Analysis was further stratified on tobacco chewing and smoking.

We obtained an increased risk of decayed (OR_{>2 decayed teeth}, 1.53; 95% CI, 1.09 to 2.16), missing teeth (OR_{>2 missing teeth}, 2.59; 95% CI, 1.99 to 3.37), and high DMFT scores (OR_{>3 DMFT score}, 2.07; 95% CI, 1.62 to 2.66). Similar results were observed on the stratified analysis. Protective effect was observed for teeth filling (OR_{>2 teeth-fillings}, 0.59; 95% CI, 0.34 to 1.03) and denture use (OR_{ever versus never used dentures}, 0.63; 95% CI, 0.47 to 0.85).

Our findings suggest that DMFT score is associated with the risk of BMC and should be included in national oral health programs for prevention of OCs, along with other indicators of oral hygiene.