tbuckley/cabot-search huggingface dataset:
Impact of colorectal cancer screening on the incidence of advanced stages of the disease in the United States: An analysis of 181,442 patients.
Authors: Nosakhare Paul Ilerhunmwuwa, Ifeanyi Uche, Mustafa Wasifuddin
Journal: Journal of Clinical Oncology (2024)

10524 Background: Routine cancer screening, in addition to identifying early-stage cancers, aim to delay the time of diagnosis of the advanced stage. The impact of screening on the incidence of advanced colorectal cancer (aCC) in real-world settings is unknown. Methods: Data of adults aged 50–74 years with regional/distant stage (advanced) colorectal cancer diagnosed between 2004 and 2020 was obtained from the Surveillance, Epidemiology, and End Results Plus Data, 17 Research Plus Registries. The age-standardized incidence rates (ASIR) and annual percentage change (APC) were used to compare incidence trends stratified by sex, race/ethnicity, area of residence, and tumor site. Results: Among 181,442 cases of aCC, 56.6% were male, 117 847 (65%) were Non-Hispanic White (NHW), 23 419 (12.9%) were Non-Hispanic Black (NHB), 22 402 (12.4%) were Hispanics, 15 787 (8.7%) were Non-Hispanic Asian or Pacific Islander (NHAPI), 1564 (0.9%) were Non-Hispanic American Indian/Alaska Native (NHAIA), and 423 (0.2%) were of unknown race, respectively. In 123 609 cases (68.1%), the tumor site was in the colon, in the rectum in 41 395 cases (22.8%), and in the recto-sigmoid junction in 16 438 cases (9.1%). From 2004 to 2020, overall ASIR of aCC decreased (APC, -1.87%: -2.37 to -1.40), especially in females (APC, -2.05%: -2.53 to -1.55 vs. male: APC, -1.84%: -2.36 to -1.29), and metropolitan residents (APC, -2.01%: -2.57 to -1.43 vs. non-metropolitan: APC, -1.36%: -1.78 to -0.92). Notably, NHB showed the greatest decrease (APC, -2.56%: -3.01 to -2.06) followed by NHW (APC, -1.95%: -2.44 to -1.47), NHAPI (APC, -1.80%: -2.25 to -1.32) and Hispanics (APC, -1.29%: -1.85 to -0.64). There was no significant change in the ASIR among NHAIA. Furthermore, the ASIR of advanced colonic (APC, -2.66%: -3.18 to -2.14) and recto-sigmoid cancers (APC, -2.35%: -2.91 to -1.65) declined, but advanced rectal cancer increased (APC, 0.58%: 0.18 to 0.98) over the same period. Conclusions: This study highlights the positive impact of colorectal cancer screening in reducing aCC incidence rates in across genders, residential areas, and racial groups/ethnicities including minority populations. While there may be other contributing factors, increased awareness and use of screening may account for the overall declining aCC incidence rates over the almost 20-year study period. Further research is essential to identify factors contributing to the screening program's limited impact on the NHAIA population and advanced rectal cancers. [Table: see text]
Evolving burden of lung cancer attributable to occupational carcinogens in 38 OECD countries: Global, national differences, age dynamics and implications for global health.
Authors: Mohit Lakkimsetti, Mihir Paresh Vanodia, Kushagrita Singh, Shrey Goel, Pinank Bathvar, Dhruval Pinalkumar Patel, Priyatha Vemparala, Juhi Patel, Vishrant Amin, Himanshu Bharatkumar Koyani, Dhruvkumar Gadhiya, Hardik Dineshbhai Desai
Journal: Journal of Clinical Oncology (2024)

10576 Background: Lung cancer (LC) remains a predominant cause of global mortality and disability, particularly significant in Organization for Economic Cooperation and Development (OECD) nations. Understanding the evolving burden of LC attributable to occupational carcinogens (OC) is critical due to its prevalence in occupational settings. Methods: Employing a standardized approach from the Global Burden of Disease study, we estimated deaths and disability-adjusted life years (DALYs) caused by lung cancer linked to OC. Our analysis spans age, gender, year, and location across the 38 OECD countries from 1990-2019. Results were presented as absolute counts and age-standardized rates (ASR) per 100,000 person-years, with projections extended to 2040 using regression frameworks. Results: Deaths from LC attributable to OC increased from 120,862 (95%UI: 91,114-148,937) in 1990 to 167,917 (127,888-208,066) in 2019, with DALYs rising from 2.4 million (1.8-3.1) to 2.9 million (2.2-3.6) over the same period. The United States recorded the highest number of deaths (41,075), followed by Japan (20,496) and the United Kingdom (15,223) in 2019. Notably, the Netherlands exhibited the highest age-standardized mortality rate (ASMR) at 12.62 cases per 100,000, with Belgium and the United Kingdom following closely. Asbestos exposure accounted for the highest number of deaths (147,263), followed by silica (15,660), arsenic (3,172), and diesel engine exhaust (2,798). Males bore a significantly higher burden than females over the last three decades, with the 75-79 age group recording the highest number of deaths (32,477) and the 70-74 age group registering the highest DALYs (613,442). Conclusions: The study underscores the escalating burden of LC attributable to occupational carcinogens across OECD countries, highlighting the imperative for robust preventive measures and targeted interventions. Urgent action is warranted to mitigate exposures to known carcinogens in occupational settings, particularly among vulnerable populations, to curb the escalating public health challenge posed by occupational lung cancer.
Evaluation of the study of control arms in randomized clinical trials of cancer.
Authors: Sandeep Kumar Jain, Marjorie Glass Zauderer, Tarsheen Sethi, Martin W. Schoen, Sam Rubinstein, Ryan Huu-Tuan Nguyen, Seema Nagpal, Sanjay Mohan, Sathwik Madireddy, Mark Lythgoe, Wayne Liang, Amit Kulkarni, Shalin Kothari, Talal Hilal, Matthew James Hadfield, Gaurav Goyal, Teja Ganta, Bhagirathbhai R. Dholaria, Alaina J. Brown, Jeremy Lyle Warner
Journal: Journal of Clinical Oncology (2024)

11023 Background: Randomized clinical trials (RCTs) in cancer typically compare experimental to control arm regimens. The choice of an appropriate control (ctrl) arm can have a major impact on the expected success of an RCT. The frequency with which cancer RCTs use control arms based on established dosing and scheduling protocols has not been described. Methods: The HemOnc knowledgebase (KB) was used to identify systemic anti-cancer therapy (SACT) regimen variants, defined as regimens with identical components that differ in dosing, scheduling, and/or route. Non-cancer, nonrandomized, and non-SACT studies were excluded. Study publication year was used to define standard variants as those evaluated in the experimental arm of a positive phase 3 RCT &gt;1 year prior to publication as a control arm, regardless of cancer type or context of treatment. Study-variant dyads were evaluated to determine whether the variant was standard. Success rates of RCTs with standard vs non-standard control arms were evaluated with Fisher’s exact test. Results: 5221 studies were associated with ≥1 named variant in the HemOnc KB, as of 2024-02-06. After exclusions, there were 3511 study-variant dyads (2386 studies; 1714 variants). The 9 most common regimens are shown in the Table. The median (IQR) number of variants per regimen was 2 (1-3); carboplatin &amp; paclitaxel (CP) had the most variants (n=33). Across all control arm study-variant dyads, 2228/3492 (64%) utilized non-standard variants. For example, 60/97 studies (62%) of docetaxel as control used the 75 mg/m2 q3wk variant after it was established in 2000, whereas n=27 others used 19 non-standard variants. Trials that used a standard control arm had a numerically higher success rate, 45% vs 42% (OR 1.10, 95% CI 0.92-1.32). Conclusions: Non-standard regimen variants are frequently used in cancer RCTs. Reasons for this could include toxicity, patient convenience, or emerging data from smaller studies that establish comparable efficacy or improved toxicity to standard variants. However, the a priori efficacy of non-standard control arms is less rigorously established, and trials with standard control arms might be more successful. Future directions include quantifying the granular differences between standard and non-standard variants and investigating whether certain types of non-standard variation (e.g. fewer cycles, lower doses) associate with trial success rates. [Table: see text]
Dietary patterns and the risk of hematological malignancy in the California Teachers study cohort.
Authors: Julijana Zoran Conic, Lily Zhiying Chen, Thomas Reske, Lobna Ali
Journal: Journal of Clinical Oncology (2024)

10545 Background: Many studies show a correlation between diet and the risk of developing cancer, but most of these studies pertain to solid tumors and data linking certain diets to hematologic malignancies is scarce. This study aims to elucidate the effect of dietary patterns on the risk of developing hematologic malignancy. This study aims to elucidate dietary patterns and correlation with the risk of developing a hematologic malignancy. Methods: Data from 106,029 women in the California Teachers Study (CTS) cohort was analyzed, 476 participants were diagnosed with lymphocytic, monocytic, or other leukemia, 895 with Hodgkin’s or non-Hodgkin’s lymphoma, and 227 with multiple myeloma between 1995-2020. Results: Five major dietary patterns were identified as: 1) plant-based diet, characterized by a high consumption of fruit and vegetables, 2) high-protein, high-fat diet characterized by a high consumption of animal proteins animal protein (e.g., meat and eggs) and added fats (e.g., butter and mayonnaise), 3) high-carbohydrate diet characterized by a high consumption of convenience foods, pasta, and bread, 4) ethnic diet characterized by a high consumption of legumes, soy-based foods, rick and dark-green leafy vegetables and 5) the salad and wine diet characterized by high consumption of salad and low-fat dressing, fish, wine, coffee and tea, using principal factors analysis (PCFA). Relative risk and confidence intervals were analyzed for each dietary pattern and their correlation to a diagnosis of a hematologic malignancy. Models were adjusted for race-ethnicity/birthplace, living/working half a mile from a chemical plan, living/working half a mile from a powerplant, cigarette use, family history of leukemia and/or lymphoma, BMI (kg/m 2 ), daily caloric intake (kcal/day), socioeconomic status, and moderate physical activity (h/wk). Overall, the high-carbohydrate diet was shown to be protective against hematologic malignancy risk with the lowest RR in all quintiles, but lowest in the 5 th quintile (RR: 0.73; 95% CI: 0.59, 0.99, p=0.004). A high-carbohydrate diet was also shown to be associated with a reduction in multiple myeloma risk specifically with the lowest RR in all quintiles, but lowest in the 5 th quintile (RR: 0.79; 95% CI: 0.63, 0.98, p=0.03). The ethnic diet was associated with a higher risk of multiple myeloma with the highest RR in all quintiles but highest in the 2 nd quintile (RR:1.21; 95% CI 1.06, 1.39, p=0.006). Conclusions: The finding that the high-carbohydrate diet is associated with a reduced risk of a hematologic malignancy warrants further research to characterize the degree of risk reduction, what specific foods, if any, in the category offer protective effects, and if it is a potential approach for prevention.
Association between rare pathogenic variants in established cancer risk genes and the diagnosis of single and multiple common cancers: A UK Biobank study.
Authors: Jeffrey Shevach, Jianfeng Xu, Nathan Snyder, Jun Wei, Zhuqing Shi, Huy Tran, S. Lilly Zheng, Ann G. Schwartz, Jennifer Lynn Beebe-Dimmer, Kathleen A. Cooney
Journal: Journal of Clinical Oncology (2024)

10505 Background: Much of our understanding of cancer risk attributable to rare pathogenic variants (RPV) is derived from family-based and case-only cohort studies, which may be limited by ascertainment bias. We sought to identify associations between RPVs and cancer diagnoses in a large population-based study. Methods: We conducted a case-control study using the UK Biobank. We performed gene-based aggregate testing to examine the relationship between RPVs (defined as pathogenic or likely pathogenic variants) in 96 genes implicated in cancer risk and the diagnosis of 11 common cancers using the combined optimal unified sequence kernel association test (SKAT-O). Odds ratios (OR) and 95% confidence intervals (CI) were then calculated using Firth logistic regression. Results were adjusted for age, sex and genetic ancestry. Bonferroni-adjusted p-values were used to determine statistical significance. Variant pathogenicity was determined by American College of Medical Genetics criteria. Results: We identified 24 genes in which RPVs were statistically significantly associated with at least one of 11 common cancers among 183,626 individuals. The presence of an RPV in one of these 24 genes was associated with increased odds of one cancer (OR 1.8; 95% CI: 1.7-2.0), and multiple cancers (OR 2.5; 95% CI: 2.2-2.9). Conclusions: This large population-based study identified 24 established cancer risk genes in which RPVs were associated with common cancers. We identified both known and novel associations between cancer and RPVs. Some associations—i.e. renal/pancreas and MEN1—may be due to ascertainment and/or misclassification bias. We also show that individuals with RPVs in cancer risk genes not only have higher odds of one cancer diagnosis, but also multiple cancers.[Table: see text]
Examining the epidemiology of AIDS-defining and HPV-associated cancers in HIV endemic areas of south Florida for development of targeted intervention.
Authors: Antonia Pryor Leavitt, Ming Lee, Lauren Nahodyl, Till Krenz, Erin N. Kobetz
Journal: Journal of Clinical Oncology (2024)

e22522 Background: The Miami-Dade and Broward Counties in South Florida (SF) have the highest incidence of HIV infection in the United States, with over 47,000 people living with HIV as of 2021. The epidemiology and burden of cancers associated with HIV in SF have not been fully described, hampering efforts for effective cancer control. This study examines the regional epidemiology of AIDS-defining cancers and HPV-associated cancers, for which HIV+ patients face higher risk. The results are used to develop education and community screening events targeting communities with high incidences of these cancers. Methods: The catchment area of Sylvester Comprehensive Cancer Center, consisting of Miami-Dade, Broward, Palm Beach, and Monroe Counties for a total population of six million was studied. Using the 2015-2019 data from Florida’s official cancer registry, age-adjusted incidences (AAI) for AIDS-defining cancers and HPV-associated cancers were calculated for all census tracts in SF. Geospatial hot spot analysis was then applied to identify statistically significant clusters (hot spots) of census tracts with high AAI of these cancers. Results: We identified two clusters of hot spots for AIDS-defining and HPV-associated cancers in SF. Except for penile cancer in one cluster, both clusters have HPV-associated cancer incidences that are significantly higher than the state averages. Specifically, one cluster has the highest incidence of anal cancer in SF, while the other has a notable concentration of penile cancer. Conclusions: Using the results, we have developed targeted educational and screening events for communities within the hot spots. A screening summit was recently held in a hot spot community where several screening and educational events were offered on a single day. By sharing information about the epidemiology of these cancers, we were able to facilitate community buy-in and develop working relationships with community partners to provide culturally competent and targeted intervention for a population who are less likely to undergo screening. [Table: see text]
A pilot study on ultra-sensitive circulating tumor DNA detection with a novel methylation amplifier probe in colorectal cancer.
Authors: Guanyi Xie, Yangjunyi Li, Xiaowen He, Shuang Guo, Liyuan Zhao, Lingjian Yang, Yalong Zhang, Min Li, Xueguang Sun, Ping Lan
Journal: Journal of Clinical Oncology (2024)

10547 Background: Liquid biopsy is extensively researched for detecting cancer-related methylation markers. However, detecting ultra-low methylation signals in liquid biopsies is extremely challenging. In early-stage cancer patients, less than 1% of circulating cell-free DNA (cfDNA) is tumor tissue-derived DNA (ctDNA), presenting a low signal-to-noise ratio for effective tumor marker detection. Methods: Here, we introduce Methylation Amplifier Probe for Low-signal Enrichment (MAPLE), a method for designing ultra-short hybrid capture probes (25-55 nt). By reducing the length of the probes, MAPLE enhances their intolerance to DNA base mismatches, thereby significantly improving their ability to specifically bind and enrich the targeted methylation haplotypes. A panel consisting of 13,218 CRC-related methylation haplotypes was constructed for validation. 42 samples from patients with cancer and 43 gender/age matched control samples were processed for the panel validation. All the DNA samples underwent bisulfite conversion, library preparation and parallelly hybridized with two capture panels composed with conventional probes (120 nt) or the MAPLE probes, demonstrating its effectiveness in increasing cancer signal-to-noise ratio in the final NGS data. Results: With MAPLE, in the final NGS data, ratio of CRC-related methylation haplotypes reads (signal) in patient’s plasma samples increased from 7% (conventional) to 28% (MAPLE). At 20M total raw reads (1000x sequencing depth), the MAPLE panel detects over four times the targeted haplotype fragments compared to the conventional panel. For a cohort including 42 patients (I-III:24, IV:18) with CRC and 43 gender/age matched controls, the MAPLE panel aided by a machine-learning classifier detected patients with a sensitivity of 0.83 and a specificity of 0.95. Conclusions: This pilot study highlights the potential of ultra-short probes in capturing cancer-related methylation haplotypes, advancing towards an early detection test for pan-cancer.
Examining 1-year mortality risk among patients with malignant melanoma undergoing immune checkpoint inhibitor therapy with a history of cannabis use.
Authors: Imtisaal Waris, Rahul Raiker, Nanda Siva, Sanya Goswami, Haig Pakhchanian, Amir Shahzad Kamran
Journal: Journal of Clinical Oncology (2024)

11046 Background: Cannabis use has become an increased topic of discussion in the United States due to rise in legalization, thereby increasing its accessibility for recreational and medicinal use in diseases like cancer. Immune Checkpoint Inhibitor (ICI) therapy has also recently been increasing in patient with metastatic cancers such as melanoma by targeting PD1 or PD-L1 receptors to manipulate the body’s immune response to induce cancer cell death. Cannabis is mediated in part by the CB1 and CB2 receptors in the endocannabinoid system that is present in the natural immune system. Due to the body’s immune response to cannabis, it is hypothesized this could interfere with the activity of ICI therapy. However, research examining this is sparse. Therefore, the goal was to assess mortality in malignant melanoma patients with a history of cannabis use who undergo ICI therapy. Methods: A retrospective cohort study was performed with TriNetX, a federated database of ~100 million patients across 84 healthcare organizations. Patients &gt;17 years from 2012-2023 were identified based on ICI-therapy initiation within 1 month of malignant melanoma diagnosis. Cohorts were then created by history of those with and without cannabis use disorder. 1:1 propensity score matching was conducted to control for confounding comorbidities and demographics. Unadjusted and adjusted hazard ratios (aHR) with 95% CI were calculated for 1-year mortality after therapy initiation. HR’s were estimated using the Cox proportional hazard model. Survival curves were compared using the log-rank test. Results: A total 14589 melanoma patients who underwent ICI therapy were identified, of which 2.3% had documented cannabis use disorder. Prior to matching, melanoma patients with cannabis history had a statistically significant higher 1-year mortality compared to those with no cannabis history (HR [95%CI] = 1.29 [1.04,1.6], log rank test: p=0.0197). After matching, two balanced cohorts of 344 patients remained and adjusting for confounders revealed that melanoma patients with cannabis history had no significant difference in 1-year mortality risk compared to patients without cannabis history (1.18 [0.87,1.6], log rank test: p=0.293). Conclusions: Cannabis use among melanoma patients was shown to not have any meaningful difference in 1-year mortality risk compared to patients without cannabis use history while undergoing ICI-therapy. Additional studies, such as examining cannabis frequency and dosage, is warranted to further examine its effect.
The single center experience with the war-related Ukrainian patients with various cancer diagnoses treated in clinical trials between 2022-2024.
Authors: Izabela Gudewicz
Journal: Journal of Clinical Oncology (2024)

e23040 Background: According to the WHO, 32% of active combat areas residents have been unable to obtain essential medicines since the beginning of the war in Ukraine. Clinical trials conducted in Poland have proven to assist oncological patients greatly. Many Ukrainian residents have Polish ancestors and are fluent in the Polish language. We decided to check whether the highest ethical standards of clinical trials make the ordinary intention to include a patient from Ukraine insufficient. Conducting a complete risk-benefit analysis allows choosing the best interest and safety of the clinical trial participant. Methods: The study aimed to evaluate the most frequent standards of oncological treatment of Ukrainian patients. We retrospectively verified the number of patients of Ukrainian nationality, in the age above 18 years treated at our center since the start of the invasion of Ukraine in February 2022 compared to the Polish patients. Results: Based on the National Health Fund data, Polish cancer centers in 2022 treated overall 994,767 patients including 8,000 patients from Ukraine. In the Pomeranian region, 3,815 patients received oncological therapies (data from the Central Statistical Office - of national). At our center in Gdansk between 01.01.2022 and 31.12.2023, therapy received 38,574 patients, including 34 Ukrainians. Clinical trials participants included 3,968 Polish and four Ukrainian patients (2 cases of malignant melanoma, one breast cancer, one lung cancer). Ukrainian patients represented 28.5%, 10%, and 8% of all patients included, respectively. Conclusions: Not prepared for the rapid influx of migrants Polish healthcare system encountered many problems like the language barrier, the need for a translator or approved documents by the Bioethics Committee, and the legal side of the informed consent form (ICF). At our center, all Ukrainian patients signed ICF in Polish. Regarding clinical trials participation, our study shows the unmet need of Ukrainian patients. The decision to include a patient has to be mutual (sponsor and investigator) and as soon as possible to ensure the required safety of each patient.