Cancer Outcomes Research Articles

Validation of miRNA signatures for ovarian cancer earlier detection in the pre-diagnosis setting using machine learning approaches.

Effective strategies for early detection of epithelial ovarian cancer are lacking. We evaluated whether a panel of 14 previously established circulating microRNAs could discriminate between cases diagnosed <2 years after serum collection and those diagnosed 2-7 years after serum collection. miRNA sequencing data from subsequent ovarian cancer cases were obtained as part of the ongoing multi-cancer JanusRNA project, utilizing pre-diagnostic serum samples from the Janus Serum Bank and linked to the Cancer Registry of Norway for cancer outcomes. We included a total of 80 ovarian cancer cases contributing 80 serum samples and compared 40 serum samples from cases with samples collected <2 years prior to diagnosis with 40 serum samples from cases with sample collection ≥2 to 7 years. We employed the extreme gradient boosting (XGBoost) algorithm to train a binary classification model using 70% of the available data, while the model was tested on the remaining 30% of the dataset. The performance of the model was evaluated using repeated holdout validation. The previously established set of miRNAs achieved a median area under the receiver operating characteristic curve (AUC) of 0.771 in the test sets. Four out of 14 miRNAs (hsa-miR-200a-3p, hsa-miR-1246, hsa-miR-203a-3p, hsa-miR-23b-3p) exhibited higher expression levels closer to diagnosis, consistent with the previously reported upregulation in cancer cases, with statistical significance observed only for hsa-miR-200a-3p (beta=0.14; p=0.04). The discrimination potential of the selected models provides evidence of the robustness of the miRNA signature for ovarian cancer.

Trends in phase 1 oncology clinical trials across Australia; Analysis of ClinicalTrials.gov 2012-2022.

Phase 1 oncology trials provide access to new therapies and may improve cancer outcomes. Phase 1 trials conducted in the Asian-Pacific region are increasing at a faster rate than the global trend. This study aimed to describe the changing landscape of phase 1 oncology trials in Australia in the last decade. This cross-sectional study reviewed phase 1 oncology trials registered on ClinicalTrials.gov conducted in Australia. Phase 1 trials were included for analysis if they enrolled adults with solid organ malignancies, used at least one systemic agent, and were first registered between January 1, 2012, and December 31, 2022. The number of trials, site locations, sponsor type, and drug class were analyzed using descriptive statistics. Over the 10-year period, ClinicalTrials.gov included 493 phase 1 clinical trials across 71 Australian sites. Most sites were in metropolitan locations; in Melbourne, trials were concentrated within selected sites, while in Sydney, trials were spread across a larger number of sites. The number of phase 1 trials per annum increased from 18 in 2012 to 75 in 2022. Since 2020, emerging biopharmaceutical companies have become the predominant sponsor type, a trend that is also seen globally. While most trial sponsors were North American (42%), there was increasing representation from Asian sponsors over the 10-year period (6% in 2012 to 39% in 2022). Immunomodulatory (45%) and targeted approaches (44%) accounted for most drug classes used alone or in combination. There are an increasing number of phase 1 trials conducted within Australia. Sponsors of phase 1 trials are increasingly from Asian countries and are more likely to be emerging biopharmaceutical companies.

Assessing the impact of the COVID-19 pandemic on patients referred to a lung cancer rapid assessment clinic in Ontario, Canada

RATIONALE The COVID-19 pandemic negatively impacted lung cancer (LC) outcomes. The Lung Diagnostic Assessment Program (LDAP) in Southeastern Ontario is a rapid assessment clinic for patients with suspected LC. OBJECTIVE Characterize the impact of COVID-19 on presentations and timeliness of care within LDAP. METHODS Retrospective study of LDAP-referred patients pre-COVID-19 (December 2019–March 2020) with matched cohorts post-COVID-19 Year 1 (December 2020–March 2021), and Year 2 (December 2021–March 2022). Data included: patient demographics, LC diagnosis, stage, timeliness of care and symptoms. Statistical analysis included unpaired t-tests and chi-squared tests. MEASUREMENTS AND MAIN RESULTS We reviewed 273 patients pre-COVID-19, 287 post-COVID-19 Year 1 and 218 Year 2. Post-COVID-19, more patients were suspected to have cancer at referral (pre-COVID-19, 28.6% vs. post-COVID-19 Year 2, 37.2%, p = 0.03), and more patients did not attend consultation (9.8%, 10.7% vs 1.0% pre-COVID-19, p = 0.0002) due to hospitalization or declining assessment. Average time from referral to consultation was longer during post-COVID-19 Year 1 (12.2 vs. 17.0 days, p = 0.003) but unchanged by Year 2; times from referral to diagnosis and treatment were unchanged across cohorts (42.7 vs. 44.1 vs. 40.9, p = NS) and (74.0 vs. 66.2, vs. 70.3, p = NS, respectively). Post-COVID-19 patients reported longer symptom duration (5.0 vs. 3.5 months, p = 0.04). CONCLUSIONS During the COVID-19 pandemic, patient characteristics and timeliness of care within LDAP were unchanged, but more patients experienced clinical decline and longer symptom duration prior to consultation. While care within LDAP was relatively insulated, barriers to care prior to referral may have contributed to later presentation.

Barriers to and opportunities for advancing racial equity in cervical cancer screening in the United States

BackgroundIn the United States (U.S.), racially minoritized people have higher rates of cervical cancer morbidity and mortality compared to white individuals as a result of racialized structural, social, economic, and health care inequities. However, cervical cancer screening guidelines are based on studies of predominately white individuals and do not substantially discuss or address racialized cervical cancer inequities and their social determinants, including racism.MethodsWe conducted in-depth interviews with health care providers (N = 30) and key informants with expertise in health equity (N = 18). We utilized semi-structured interview guides that addressed providers’ views and experiences delivering cervical cancer screening to racially minoritized individuals and key informants’ recommendations for advancing racial equity in the development and implementation of cervical cancer screening guidelines. Interviews were analyzed using a template style thematic analysis approach involving deductive and inductive coding, memo writing, and matrix analysis for theme development.ResultsMost health care providers adopted a universal, one-size-fits-all approach to cervical cancer screening with the stated goal of ensuring racial equality. Despite frequently acknowledging the existence of racialized cervical cancer inequities, few providers recognized the role of social inequities in influencing them, and none discussed the impact of racism. In contrast, key informants overwhelmingly recommended that providers adopt an approach to cervical cancer screening and follow-up care that recognizes the role of racism in shaping racialized cervical cancer and related social inequities, is developed in partnership with racially minoritized communities, and involves person-centered, structurally-competent, and trauma-informed practices that address racially minoritized peoples' unique lived experiences in historical and social context. This racism-conscious approach is not to be confused with race-based medicine, which is an essentialist and racist approach to health care that treats race as a biological variable rather than as a social and political construct.ConclusionsDevelopers and implementers of cervical cancer screening guidelines should explicitly recognize and address the impact of racism on cervical cancer screening, follow-up care, and outcomes, meaningfully incorporate racially minoritized communities' perspectives and experiences, and facilitate provider- and institutional-level practices that foster racial equity in cervical cancer.

Comprehensive Analysis of the Function and Prognostic Value of TAS2Rs Family-Related Genes in Colon Cancer.

In the realm of colon carcinoma, significant genetic and epigenetic diversity is observed, underscoring the necessity for tailored prognostic features that can guide personalized therapeutic strategies. In this study, we explored the association between the type 2 bitter taste receptor (TAS2Rs) family-related genes and colon cancer using RNA-sequencing and clinical datasets from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Our preliminary analysis identified seven TAS2Rs genes associated with survival using univariate Cox regression analysis, all of which were observed to be overexpressed in colon cancer. Subsequently, based on these seven TAS2Rs prognostic genes, two colon cancer molecular subtypes (Cluster A and Cluster B) were defined. These subtypes exhibited distinct prognostic and immune characteristics, with Cluster A characterized by low immune cell infiltration and less favorable outcomes, while Cluster B was associated with high immune cell infiltration and better prognosis. Finally, we developed a robust scoring system using a gradient boosting machine (GBM) approach, integrated with the gene-pairing method, to predict the prognosis of colon cancer patients. This machine learning model could improve our predictive accuracy for colon cancer outcomes, underscoring its value in the precision oncology framework.

Machine Learning and External Validation of the IDENTIFY Risk Calculator for Patients with Haematuria Referred to Secondary Care for Suspected Urinary Tract Cancer

BackgroundThe IDENTIFY study developed a model to predict urinary tract cancer using patient characteristics from a large multicentre, international cohort of patients referred with haematuria. In addition to calculating an individual’s cancer risk, it proposes thresholds to stratify them into very-low-risk (<1%), low-risk (1–<5%), intermediate-risk (5–<20%), and high-risk (≥20%) groups. ObjectiveTo externally validate the IDENTIFY haematuria risk calculator and compare traditional regression with machine learning algorithms. Design, setting, and participantsProspective data were collected on patients referred to secondary care with new haematuria. Data were collected for patient variables included in the IDENTIFY risk calculator, cancer outcome, and TNM staging. Machine learning methods were used to evaluate whether better models than those developed with traditional regression methods existed. Outcome measurements and statistical analysisThe area under the receiver operating characteristic curve (AUC) for the detection of urinary tract cancer, calibration coefficient, calibration in the large (CITL), and Brier score were determined. Results and limitationsThere were 3582 patients in the validation cohort. The development and validation cohorts were well matched. The AUC of the IDENTIFY risk calculator on the validation cohort was 0.78. This improved to 0.80 on a subanalysis of urothelial cancer prevalent countries alone, with a calibration slope of 1.04, CITL of 0.24, and Brier score of 0.14. The best machine learning model was Random Forest, which achieved an AUC of 0.76 on the validation cohort. There were no cancers stratified to the very-low-risk group in the validation cohort. Most cancers were stratified to the intermediate- and high-risk groups, with more aggressive cancers in higher-risk groups. ConclusionsThe IDENTIFY risk calculator performed well at predicting cancer in patients referred with haematuria on external validation. This tool can be used by urologists to better counsel patients on their cancer risks, to prioritise diagnostic resources on appropriate patients, and to avoid unnecessary invasive procedures in those with a very low risk of cancer. Patient summaryWe previously developed a calculator that predicts patients’ risk of cancer when they have blood in their urine, based on their personal characteristics. We have validated this risk calculator, by testing it on a separate group of patients to ensure that it works as expected. Most patients found to have cancer tended to be in the higher-risk groups and had more aggressive types of cancer with a higher risk. This tool can be used by clinicians to fast-track high-risk patients based on the calculator and investigate them more thoroughly.

Impact of hormone receptor status and tumor subtypes of breast cancer in young BRCA carriers

Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its impact on prognosis of young patients harboring BRCA pathogenic variant (PV). This international, multicenter, retrospective cohort study included young patients (≤40 years) diagnosed with invasive breast cancer and harboring germline PV in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest (disease-free survival [DFS], breast cancer specific survival [BCSS] and overall survival [OS]) were first investigated according to hormone receptors expression (positive vs. negative), and then according to breast cancer subtype (luminal A-like vs. luminal B-like vs. triple-negative vs. HER2-positive breast cancer). From 78 centers worldwide, 4,709 BRCA carriers were included, of whom 2,143 (45.5%) had hormone receptor-positive and 2,566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% vs. 9.6%, p<0.001), while the rate of second primary breast cancer was lower (9.1% vs. 14.7%, p<0.001) compared to patients with hormone receptor-negative disease. The 8-years DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive vs. negative disease changed over time for DFS, BCSS, and OS (p<0.05 for interactions of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-years DFS: 60.8% in luminal A-like vs. 63.5% in triple-negative vs. 65.5% in HER2-positive and 69.7% in luminal B-like subtype). In young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor-positive vs. negative disease warrants consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.

Impact of Bowel Preparation Quality on Colonoscopy Findings and Colorectal Cancer Deaths in a Nation-Wide Colorectal Cancer Screening Program.

Adequate bowel preparation is paramount for a high-quality screening colonoscopy. Despite the importance of adequate bowel preparation, there is a lack of large studies that associated the degree of bowel preparation with long-term colorectal cancer outcomes in screening patients. In a large population-based screening program database in Austria, quality of bowel preparation was estimated according to the Aronchick Scale by the endoscopist (excellent, good, fair, poor, and inadequate bowel preparation). We used logistic regression to assess the influence of bowel preparation on the detection of different polyp types and the interphysician variation in bowel preparation scoring. Time-to-event analyses were performed to investigate the association of bowel preparation with postcolonoscopy colorectal cancer (PCCRC) death. A total of 335,466 colonoscopies between January 2012 and follow-up until December 2022 were eligible for the analyses. As compared with excellent bowel preparation, adenoma detection was not significantly lower for good bowel preparation (odds ratio 1.01, 95% confidence interval [CI] 0.9971-1.0329, P = 0.1023); however, adenoma detection was significantly lower in fair bowel preparation (odds ratio 0.97, 95% CI 0.9408-0.9939, P = 0.0166). Individuals who had fair or lower bowel preparation at screening colonoscopy had significantly higher hazards for PCCRC death (hazard ratio for fair bowel preparation 2.56, 95% CI 1.67-3.94, P < 0.001). Fair bowel preparation on the Aronchick Scale was not only associated with a lower adenoma detection probability but also with increased risk of PCCRC death. Efforts should be made to increase bowel cleansing above fair scores.

Racial disparities in colorectal cancer outcomes and access to care: a multi-cohort analysis.

Non-Hispanic Black (NHB) Americans have a higher incidence of colorectal cancer (CRC) and worse survival than non-Hispanic white (NHW) Americans, but the relative contributions of biological versus access to care remain poorly characterized. This study used two nationwide cohorts in different healthcare contexts to study health system effects on this disparity. We used data from the Surveillance, Epidemiology, and End Results (SEER) registry as well as the United States Veterans Health Administration (VA) to identify adults diagnosed with colorectal cancer between 2010 and 2020 who identified as non-Hispanic Black (NHB) or non-Hispanic white (NHW). Stratified survival analyses were performed using a primary endpoint of overall survival, and sensitivity analyses were performed using cancer-specific survival. We identified 263,893 CRC patients in the SEER registry (36,662 (14%) NHB; 226,271 (86%) NHW) and 24,375 VA patients (4,860 (20%) NHB; 19,515 (80%) NHW). In the SEER registry, NHB patients had worse OS than NHW patients: median OS of 57 months (95% confidence interval (CI) 55-58) versus 72 months (95% CI 71-73) (hazard ratio (HR) 1.14, 95% CI 1.12-1.15, p = 0.001). In contrast, VA NHB median OS was 65 months (95% CI 62-69) versus NHW 69 months (95% CI 97-71) (HR 1.02, 95% CI 0.98-1.07, p = 0.375). There was significant interaction in the SEER registry between race and Medicare age eligibility (p < 0.001); NHB race had more effect in patients <65 years old (HR 1.44, 95% CI 1.39-1.49, p < 0.001) than in those ≥65 (HR 1.13, 95% CI 1.11-1.15, p < 0.001). In the VA, age stratification was not significant (p = 0.21). Racial disparities in CRC survival in the general US population are significantly attenuated in Medicare-aged patients. This pattern is not present in the VA, suggesting that access to care may be an important component of racial disparities in this disease.

Tumor-intrinsic and Cancer-associated Fibroblast Subtypes Independently Predict Outcomes in Pancreatic Cancer.

To assess the utility of tumor-intrinsic and cancer-associated fibroblast (CAF) subtypes of pancreatic ductal adenocarcinoma (PDAC) in predicting response to neoadjuvant therapy (NAT) and overall survival. PDAC remains a deadly disease with limited treatment options, and both the tumor as well as the microenvironment play an important role in pathogenesis. Gene expression-based tumor-intrinsic subtypes (classical and basal-like) have been shown to predict outcomes, but tumor microenvironment subtypes are still evolving. RNA-sequencing was performed on 114 deidentified resected PDAC tumors. Clinical data were collected by retrospective chart review. Single sample classifiers (SSCs) were used to determine classical and basal-like subtypes as well as tumor-permissive permCAF and tumor-restraining restCAF subtypes. Survival was analyzed using log-rank test. Patients who received NAT had an increase in overall survival (OS), with median survival of 27.9 months compared to 20.1 months for those who did not receive NAT, but the difference did not reach statistical significance (HR 0.64, P=0.076). Either tumor-intrinsic or CAF subtypes alone were associated with OS regardless of NAT or no NAT, and patients with classical or restCAF subtype had the best outcomes. When evaluated together, patients with classical-restCAF subtype had the best OS and basal-permCAF the worst OS (P<0.0001). NAT patients with classical-restCAF subtype demonstrated the longest OS compared to the other groups (P=0.00041). CAF subtypes have an additive effect over tumor-intrinsic subtypes in predicting survival with or without neoadjuvant FOLFIRINOX in PDAC. Molecular subtyping of both tumor and CAF compartments of PDAC may be important steps in selecting first-line systemic therapy.

Evaluation of antitumor potential of an anti-glypican-1 monoclonal antibody in preclinical lung cancer models reveals a distinct mechanism of action.

The main objective of this study was to investigate the antitumor effect of a mouse anti-human glypican-1 (GPC1) monoclonal antibody (mAb) on non-small cell lung carcinoma (NSCLC) and associated molecular mechanisms. The anti-proliferative and anti-migratory activities of anti-GPC1 mAb were examined in A549 and H460 NSCLC cells and LL97A lung fibroblasts. The inhibitory effect of anti-GPC1 mAb on tumor growth was evaluated in an orthotopic lung tumor model. The in vitro study showed that anti-GPC1 mAb profoundly inhibited the anchorage-independent growth of A549 and H460 NSCLC cells and exhibited relatively high cytotoxic activities towards LL97A lung fibroblasts, A549/LL97A and H460/LL97A coculture spheroids. Moreover, anti-GPC1 mAb significantly decreased the expression of phospho-Src (p-Src; Tyr416), p-Akt (Ser473) and β-catenin in the co-cultured LL97A lung fibroblasts, and the expression of phospho-mitogen-activated protein kinase kinase (p-MEK; Ser217/221) and phospho-90 kDa ribosomal s6 kinase (p-p90RSK; Ser380) in co-cultured A549 cells. When anti-GPC1 mAb was administered to tumor-bearing mice, the inhibitory effect of anti-GPC1 mAb on the orthotopic lung tumor growth was not statistically significant. Nonetheless, results of Western blot analysis showed significant decrease in the phosphorylation of fibroblast growth factor receptor 1 (FGFR1) at Tyr766, Src at Tyr416, extracellular signal-regulated kinase (ERK) at Thr202/Tyr204, 90 kDa ribosomal S6 kinase (RSK) at Ser380, glycogen synthase kinases 3α (GSK3α) at Ser21 and GSK3β at Ser9 in tumor tissues. These data implicate that anti-GPC1 mAb treatment impairs the interaction between tumor cells and tumor associated fibroblasts by attenuating the paracrine FGFR signal transduction. The relatively potent cytotoxicity of anti-GPC1 mAb in lung fibroblasts and its potential inhibitory effect on the paracrine FGFR signal transduction warrant further studies on the combined use of this mAb with targeted therapeutics to improve therapeutic outcomes in lung cancer.

Survival outcomes and failure patterns for oropharyngeal cancers treated with simultaneous integrated boost in intensity modulated radiotherapy (SIB-IMRT) and concurrent chemotherapy.

Intensity modulated radiotherapy (IMRT) has become a standard radiotherapy treatment delivery option owing to the advantages it offers in terms of target coverage and organ sparing. Furthermore, the ability to introduce different fractionation for different targets lets us deliver higher doses to the high-risk areas and lower doses to the elective volumes at the same sitting, referred to as simultaneous integrated boost (SIB). In the current study, we intended to retrospectively analyze the clinical outcomes and patterns of the failure of oropharyngeal cancers treated with SIB-IMRT and concurrent chemotherapy at our centre and analyze the factors contributing to poorer outcomes. Data of oropharyngeal cancer patients treated with SIB-IMRT and concurrent chemotherapy were retrieved from the institutional database. Patient demographic details, histopathological features, staging, treatment details, failure patterns and outcomes were documented. All potential factors were evaluated for outcomes. Radiation was delivered by using the SIB-IMRT technique. High-risk planning target volume (PTV) received 66 Gy in 2.2 Gy/fraction, intermediate and low-risk PTV received 60 Gy and 54 Gy, respectively. Primary endpoint was to assess local control (LC), regional control (RC) and loco-regional control (LRC) rates and secondary end point was to evaluate the survival outcomes - overall survival (OS) and cancer-specific mortality. All survival analyzes were performed using the Kaplan-Meier method. A total of 169 cases were included in the final analysis. The median age was 55 years (range 20-78) with 95.3% males. The base of tongue was the most common primary site. Around 54% cases were node negative with 38% patients having stage IV disease. The local control rates for N0 vs. N+ cases were 74.1 vs. 62.3% (P = 0.046), respectively. Similarly, the 4-year RC rates for N0 vs. N+ cases were 94.4 vs. 83.5% (P = 0.024), respectively. On multivariate analysis, only 4-year RC rates showed significant difference between the two (P = 0.039). No differences were found between T stages in LRC and OS. The 4-year LRC rates for stages 1, 2 vs. 3, 4 were non-significant (69.2 vs. 66.3%; P = 0.178). The 4-year OS rate was 81.3%. The 4-year LC and LRC rates were 67.8 and 89.5%, respectively. There were 54 local and 17 regional failures. The median time to failure was 13 months (range 3.6-82.9). SIB-IMRT provides comparable outcomes for oropharyngeal cancers. OS and loco-regional recurrences were significantly worse for nodal positive disease.

Communicating prostate cancer outcomes data to consumers[sbnd] A brief communication

ObjectiveTo translate and communicate outcomes data for prostate cancer from a clinical registry data into a consumer-friendly resource. MethodsFirst, we analyzed real-world data from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC) registry for men diagnosed from 2008 to 2018 including clinical and functional outcomes following surgery, external beam radiotherapy, brachytherapy, hormone therapy, active surveillance and watchful waiting. These outcomes included overall survival, cancer specific survival, biochemical recurrence, decline in functional outcomes, and transition to active treatment following active surveillance. Second, we translated outcomes into a summary text and pictographic format and present in one document that consumers found easy to understand and interpret. This “Prostate Cancer Outcomes Report Card” was developed in consultation with a consumer advisory group and further improved through exploratory interviews with people affected by prostate cancer, an online survey among the general public, and clinician feedback. ResultsThe 5-year prostate cancer-specific survival rate was 97%. There is a reasonably high chance of cancer returning within 5 years (17% after surgery and 14% after radiotherapy) while 1 in 3 men on active surveillance transitioned to other treatments within 5 years. Sexual function was negatively affected following all treatment types. Men with higher risk disease had a worse prognosis, a higher chance of recurrence and greater decline in physical function. Consumers required trustworthy, comprehensive, simple and up-to-date information collated in one place, and valued having access to this resource. Data on high survival rates were considered reassuring. There were high levels of unmet psychosocial and supportive care needs, especially in relation to mental health and sexual function. The report card was well received by patients and health care workers. ConclusionsThis relatively simple and easily understandable consumer-oriented outcome report serves to better inform men with prostate cancer and facilitate patient-provider communication and shared decision-making.

Outcome of Obstructing vs Nonobstructing Colorectal Carcinomas: Comparative Study at Tertiary Care Hospital in Kashmir.

Colorectal cancer (CRC) is the commonly diagnosed malignancy presenting either in obstruction or without obstruction. Bowel obstruction (BO) is usually a complication of advanced cancer, significantly reducing the quality of life. We aimed to study the outcomes of these obstructed colorectal cancers requiring emergency intervention and compare it with nonobstructed cancers. In our observational comparative study, patients were divided into groups on basis of their presentation and site of lesion: nonobstructing colon group/obstructing colon group nonobstructing rectum group/obstructing rectum group. A total of 232 patients with known modes of presentation between 2015 and 2018 were included; 144 colonic, 88 rectal carcinomas with 71 being completely obstructive ones. Our study showed higher recurrence in obstructive groups with local recurrence being more common. The median interval for recurrence was early in obstructive group (p < 0.001*). The overall 5-year survival rates were better in Nonobstructing colon group, (p = -0.046* in OR vs NOR) (p = -0.031* in OC vs NOC). 5-year disease-free survival rates statistically insignificant (p = 0.203 in NOC and OC groups), (p = 0.307 in NOR and OR groups). Immediate post-op, complications except for SSI, there was no significant difference between the two groups. Our study showed higher proportion of R0 resection in NOC groups as compared with obstructive groups (p = 0.021* in in OC vs NOC and p = 0.037* in OR vs NOR) with better lymph node retrieval in NOC groups. On comparing outcome of patients who had completed multi-modal therapy in both groups, there was significantly better outcome for patients who have presented without obstruction. Ul Haq MF, Bhat GA, Wani MA, et al. Outcome of Obstructing vs Nonobstructing Colorectal Carcinomas: Comparative Study at Tertiary Care Hospital in Kashmir. Euroasian J Hepato-Gastroenterol 2024;14(1):75-80.

Advancements in Machine Learning (ML): Transforming the Future of Blood Cancer Detection and Outcome Prediction

Advancements in Machine Learning (ML): Transforming the Future of Blood Cancer Detection and Outcome Prediction

The Potential Adverse Impact of Post-Treatment Thrombocytopenia on Clinical Outcomes in Cancer Patients Treated With Immune Checkpoint Inhibitors.

The main goal of this study is to explore the prognostic and predictive implications of post-treatment thrombocytopenia on treatment efficacy and clinical outcomes in advanced-stage cancer treated with immune checkpoint inhibitors (ICIs). This retrospective study included 102 patients with advanced-stage cancer who were treated with ICIs. The simultaneous administration of chemotherapy and ICIs was omitted; nevertheless, the selection of chemotherapy agents employed in different treatment lines was left to the discretion of the attending clinician. Patients were stratified into distinct cohorts based on their post-treatment platelet counts (evaluated for up to four to six months after the completion of ICI). The primary endpoint of interest was progression-free survival (PFS), and overall survival (OS) was the secondary endpoint. Patients with superior Eastern Cooperative Oncology Group (ECOG) performance status and those who received ICI as second-line treatment displayed markedly elevated incidences of grade 1 thrombocytopenia (p < 0.05). Kaplan-Meier survival analysis confirmed that patients with high-grade thrombocytopenia had significantly shorter PFS (six vs. 13 vs. 19 months, p < 0.0001) and OS (10 vs. 21 vs. 25 months, p < 0.0001) than those with lower grades or without thrombocytopenia, respectively. Multivariate analysis revealed that decreased platelet levels were a negative independent prognostic factor for both PFS and OS in patients with advanced-stage cancer who received ICIs. The results of this retrospective study suggest that a decline in platelet levels after treatment represents a dependable adverse prognostic biomarker for clinical outcomes. Moreover, a decrease in platelet levels has been linked to reduced treatment efficacy in advanced-stage cancer patients receiving ICIs, thereby providing valuable prognostic insights for the implementation of personalized treatment strategies in cancer immunotherapy.

Evidence of RNA polymerase III recruitment and transcription at protein-coding gene promoters.

RNA polymerase (Pol) I, II, and III are most commonly described as having distinct roles in synthesizing ribosomal RNA (rRNA), messenger RNA (mRNA), and specific small noncoding (nc)RNAs, respectively. This delineation of transcriptional responsibilities is not definitive, however, as evidenced by instances of Pol II recruitment to genes conventionally transcribed by Pol III, including the co-transcription of RPPH1 - the catalytic RNA component of RNase P. A comprehensive understanding of the interplay between RNA polymerase complexes remains lacking, however, due to limited comparative analyses for all three enzymes. To address this gap, we applied a uniform framework for quantifying global Pol I, II, and III occupancies that integrates currently available human RNA polymerase ChIP-seq datasets. Occupancy maps are combined with a comprehensive multi-class promoter set that includes protein-coding genes, noncoding genes, and repetitive elements. While our genomic survey appropriately identifies recruitment of Pol I, II, and III to canonical target genes, we unexpectedly discover widespread recruitment of the Pol III machinery to promoters of specific protein-coding genes, supported by colocalization patterns observed for several Pol III-specific subunits. We show that Pol III-occupied Pol II promoters are enriched for small, nascent RNA reads terminating in a run of 4 Ts, a unique hallmark of Pol III transcription termination and evidence of active Pol III activity at these sites. Pol III disruption differentially modulates the expression of Pol III-occupied coding genes, which are functionally enriched for ribosomal proteins and genes broadly linked to unfavorable outcomes in cancer. Our map also identifies additional, currently unannotated genomic elements occupied by Pol III with clear signatures of nascent RNA species that are sensitive to disruption of La (SSB) - a Pol III-related RNA chaperone protein. These findings reshape our current understanding of the interplay between Pols II and III and identify potentially novel small ncRNAs with broad implications for gene regulatory paradigms and RNA biology.

Epidemiology of early vs late recurrence among women with early stage estrogen receptor–positive breast cancer in the Pathways Study

Abstract Background Relatively little is known about the differences in prognostic factors for early vs late recurrence among women with early stage estrogen receptor–positive breast cancer. Methods We analyzed factors related to early (&amp;lt;5 years) vs late (≥5 years) recurrence in 2992 women with stage I-IIB estrogen receptor–positive breast cancer in the Pathways Study, a prospective cohort of women with breast cancer enrolled between 2006 and 2013, with ascertainment of recurrence and death through December 2021. Results After a median follow-up of 13.3 years, 341 (13.8%) women had recurrences, including 181 (53.7%) with late recurrence. Higher stage and grade were associated with recurrence regardless of timing, whereas progesterone receptor negativity was associated with early but not late recurrence. Receipt of endocrine therapy was associated with reduced risk of overall recurrence, but the length of endocrine therapy was not statistically significant in multivariable models. Minoritized racial and ethnic groups, including Asian, Black, and Hispanic women, had higher risk of early but not late recurrence compared to non-Hispanic White women. The trend of higher risk of early recurrence among these groups remained after adjustment for clinical, demographic, and socioeconomic factors but was statistically significant only in Asian women. Conclusions Our study revealed potentially important distinctions for early vs late recurrence, including the associations with progesterone receptor negativity and self-identified race and ethnicity. Possible higher risk of early recurrence among Asian, Black, and Hispanic women provides novel evidence for the existence of disparities in cancer outcomes, even within the breast cancer subtype indicative of generally good prognosis.

ASO Visual Abstract: Overall Volume of Upper Gastrointestinal Surgery Positively Impacts Gastric Cancer Outcomes at Centers with Low Gastrectomy Volume.

ASO Visual Abstract: Overall Volume of Upper Gastrointestinal Surgery Positively Impacts Gastric Cancer Outcomes at Centers with Low Gastrectomy Volume.

Association of depressive symptoms and sleep disturbances with survival among US adult cancer survivors

BackgroundDepression and sleep disturbances are associated with increased risks of various diseases and mortality, but their impacts on mortality in cancer survivors remain unclear. The objective of this study was to characterize the independent and joint associations of depressive symptoms and sleep disturbances with mortality outcomes in cancer survivors.MethodsThis population-based prospective cohort study included cancer survivors aged ≥ 20 years (n = 2947; weighted population, 21,003,811) from the National Health and Nutrition Examination Survey (NHANES) 2007–2018 cycles. Depressive symptoms and sleep disturbances were self-reported. Depressive symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9). Death outcomes were determined by correlation with National Death Index records through December 31, 2019. Primary outcomes included all-cause, cancer-specific, and noncancer mortality.ResultsDuring the median follow-up of 69 months (interquartile range, 37–109 months), 686 deaths occurred: 240 participants died from cancer, 146 from heart disease, and 300 from other causes. Separate analyses revealed that compared with a PHQ-9 score (0–4), a PHQ-9 score (5–9) was associated with a greater risk of all-cause mortality (hazard ratio [HR], 1.28; 95% CI, 1.03–1.59), and a PHQ-9 score (≥ 10) was associated with greater risk of all-cause mortality (HR, 1.37; 95% CI, 1.04–1.80) and noncancer mortality (HR, 1.45; 95% CI, 1.01–2.10). Single sleep disturbances were not associated with mortality risk. In joint analyses, the combination of a PHQ-9 score ≥ 5 and no sleep disturbances, but not sleep disturbances, was associated with increased risks of all-cause mortality, cancer-specific mortality, and noncancer mortality. Specifically, compared with individuals with a PHQ-9 score of 0–4 and no sleep disturbances, HRs for all-cause mortality and noncancer mortality in individuals with a PHQ-9 score of 5–9 and no sleep disturbances were 1.72 (1.21–2.44) and 1.69 (1.10–2.61), respectively, and 2.61 (1.43–4.78) and 2.77 (1.27–6.07), respectively, in individuals with a PHQ-9 score ≥ 10 and no sleep disturbances; HRs for cancer-specific mortality in individuals with a PHQ-9 score ≥ 5 and no sleep disturbances were 1.95 (1.16–3.27).ConclusionsDepressive symptoms were linked to a high risk of mortality in cancer survivors. The combination of a PHQ-9 score (≥ 5) and an absence of self-perceived sleep disturbances was associated with greater all-cause mortality, cancer-specific mortality, and noncancer mortality risks, particularly in individuals with a PHQ-9 score (≥ 10).