tbuckley/cabot-search huggingface dataset:
Characteristics and pregnancy outcomes of pregnant women by cancer diagnosis status.
Authors: Usha Periyanayagam, Lyuba Popadic, Francesca Devine, Yuqin Wei
Journal: Journal of Clinical Oncology (2024)

11038 Background: Given the broad exclusion of pregnant patients from clinical trials, limited evidence exists on the impact of cancer diagnoses on pregnancy outcomes. This study aimed to describe patient characteristics and end of pregnancy events among women with and without a cancer diagnosis before pregnancy. Methods: This retrospective claims study used data from the Komodo Research Dataset between 01/01/2016–08/31/2023 to identify adult women with a known gestation of pregnancy record and end of pregnancy outcome. Eligible members needed to be continuously enrolled in medical and prescription drug plans for both 365 days before (baseline) and after the derived pregnancy start (index date). This pregnancy cohort was then stratified according to cancer status, evidenced by any cancer diagnosis during the baseline period, to allow assessment of pregnancy outcomes. Valid pregnancy outcomes included full or preterm live birth and pregnancy loss such as miscarriage, stillbirth, and elective termination. Only the earliest pregnancy observed for each eligible member was analyzed. Results: Among the 1,921,866 pregnant women included in the analyses, only 0.7% (N=12,723) of patients had any cancer diagnosis in the year prior to pregnancy start. Cancer patients were older than non-cancer patients (mean age: 33.8 and 29.2 years, respectively). Commercial medical insurance was more common (67.7% vs. 58.9%) among cancer vs. non-cancer patients and Medicaid enrollment was less common (30.3% vs. 40.6%) upon pregnancy start. The proportion of patients with a live birth was lower among cancer vs. non-cancer patients (59.7% vs. 67.1%), while the proportion with pregnancy loss was higher (31.6% vs. 25.8%). Medicaid enrollment was more common among patients that had a pregnancy loss relative to live birth for both cancer and non-cancer patients (35.5% vs. 27.5% and 45.7% vs. 38.7%, respectively). The proportion of black patients was higher among patients with a pregnancy loss relative to those with live birth in both cohorts (cancer: 11.1% vs. 8.3%; non-cancer: 16.9% vs. 13.7%), while the proportion of white patients was similar for cancer patients with a pregnancy loss vs. live birth (37.4% vs. 37.1%) and the proportion was lower for non-cancer patients (30.4% vs. 34.4%). Conclusions: Preliminary findings suggest pregnancy loss was more common among cancer patients than non-cancer patients. Regardless of cancer status, differences in insurance coverage and race were observed for patients with a live birth relative to patients with pregnancy loss. Additional research should be conducted to identify factors driving differences in pregnancy outcomes, such as in care management by race and ethnicity, particularly among the vulnerable population of cancer patients.
Pathogenic germline variant discovery in plasma cell disorders: Insights from genetic counseling referrals and testing.
Authors: Saoirse Bodnar, Tehilla Brander, Manisha M Balwani, Sundar Jagannath, Samir Parekh, Santiago Thibaud
Journal: Journal of Clinical Oncology (2024)

10619 Background: Our research has shown that 10% of multiple myeloma (MM) patients harbor pathogenic or likely-pathogenic germline variants (PGVs) in cancer predisposition genes, with a significant enrichment observed in BRCA1/2 genes. PGVs are notably more common in younger MM patients and those with a personal or familial cancer history. This study presents our experience in referring plasma cell disorder (PCD) patients at increased risk for carrying PGVs, due to either clinical history or suspicious tumor NGS findings, for genetic counseling and subsequent germline testing. Methods: This retrospective study reviewed patient records from our institution's PCD clinic, focusing on those referred for a genetic evaluation between 2020 and 2024 due to suspected cancer predisposition. We compiled demographic and clinical data for these patients, reasons for referral, and cancer history of patients and their families. The uptake of germline testing, identified mutations, and subsequent recommendations for advanced cancer surveillance and prevention, including cascade testing, were also analyzed. Germline testing utilized targeted hereditary cancer panels from five companies and was conducted on DNA samples extracted from peripheral blood, saliva/buccal swabs, or skin biopsies. Results: 52 PCD patients underwent a genetic evaluation and were included in this review, comprising 31 MM, 9 smoldering MM, and 12 MGUS cases. Median age at the time of referral was 63, and 54% of patients were female. Racial composition was 62% White, 15% Black/African-American, 12% Hispanic, 2% Asian, with 10% undisclosed. 8 patients were referred due to suspicious findings in tumor NGS, while the rest were referred due to clinical suspicion. A personal history of cancer was reported by 19 patients (37%), and 49 had a first- or second-degree relative with cancer (94%). 38 patients (73%) underwent germline testing, of which 15 (39%) harbored PGVs (11 had MM, 4 had smoldering MM). 8 PGV carriers had well-established founder variants. The remaining 7 had PGVs in genes including BRCA2 (n=3), PALB2 (n=1), BLM (n=1), SMAD4 (n=1) and NTHL1 (n=1). Of note, all 8 referred for suspicious findings in tumor NGS were confirmed to harbor PGVs. All PGV-positive patients were recommended for cascade testing and enhanced cancer screening. Conclusions: Our findings indicate a 39% PGV detection rate in PCD patients referred for genetic evaluation, underscoring the potential benefit of implementing screening guidelines in this population. PGV detection led to recommendations for intensified surveillance and cascade testing in all cases, impacting both patients and their families. The discovery of BRCA2PGVs in 20% (3/15) of cases reinforces its potential role as a predisposition gene in MM, corroborating our prior findings.
Association of frailty assessed by a ten-item frailty index (FI-CGA-10) with health-related quality of life in older adults with cancer.
Authors: Tomohiro F. Nishijima, Mototsugu Shimokawa, Kirsten A. Nyrop, Kohei Arimizu, Taito Esaki, Masaru Morita, Yasushi Toh, Hyman Muss
Journal: Journal of Clinical Oncology (2024)

11047 Background: A 10-item frailty index based on a comprehensive geriatric assessment (FI-CGA-10) is a recently developed measure of frailty in the geriatric oncology setting [Oncologist, 26, e1751 (2021)]. Our objective was to investigate the association between frailty defined by the FI-CGA-10 and health-related quality of life (HRQOL) in older adults with cancer. Methods: This study included 1015 consecutive older adults with cancer who underwent a CGA before cancer treatment decision at a geriatric oncology service in Japan from February 2020 through September 2023. Fitness and frailty level was evaluated using the FI-CGA-10 that assesses 10 domains: cognition, mood, communication, mobility, balance, nutrition, base and instrumental activities of daily living, social support, and comorbidity. Deficits in each domain were scored as 0 (no problem), 0.5 (minor problem), and 1.0 (major problem). FI-CGA-10 scores (range 0-1) were calculated by dividing the sum of the scores for each domain by 10 and then categorized as fit (&lt;0.2), pre-frail (0.2–0.35), and frail (&gt;0.35). HRQOL was measured by the EQ-5D-5L index score and visual analogue scale (VAS) at the CGA consultation. The minimally important difference (MID) values for the EQ-5D-5L Japan-based index and VAS scores are 0.048 and 7, respectively. Associations between EQ-5D-5L and FI-CGA-10 scores were analyzed by Pearson’s correlation and linear regression models adjusting for covariates (age, sex, cancer type, and stage). Results: Median age was 80 years, 60% were male, and 68% had gastrointestinal cancer. The mean +- SD of the FI-CGA-10 score was 0.35 +- 0.19. The FI-CGA-10 negatively correlated with the EQ-5D-5L index (Pearson’s r = -0.69; 95% CI -0.72 to -0.66; P&lt;.001) and VAS (r = -0.47; 95% CI -0.52 to -0.42; P&lt;.001) scores. After adjusting for the covariates, each 0.1 unit increase in FI-CGA-10 score was associated with 0.070 decrease in EQ-5D-5L index (95% CI -0.075 to -0.066; P&lt;.001) and 4.9 decrease in VAS scores (95% CI -5.5 to -4.4; P&lt;.001). Using the three-level classification, 22% of patients (n = 221) were categorized as fit, 38% (n = 384) as pre-frail, and 40% (n =410) as frail. Overall, the fit group had the highest EQ-5D-5L index and VAS scores followed by the pre-frail and frail groups (table). The score differences between the frailty categories were statistically significant and clinically meaningful according to the MID values. Conclusions: This study demonstrated that frailty assessed by the FI-CGA-10 cross-sectionally correlated with HRQOL measured by the EQ-5D-5L in older Japanese adults with cancer. The observed association further supports construct validity of the FI-CGA-10 as a CGA-based frailty measure. [Table: see text]
Multidisciplinary PAIN management features of pediatric oncology patients in a pediatric cancer center in Turkiye: A developing country experience.
Authors: Nurdan Tacyildiz, Sonay Incesoy Ozdemir, CEM Canakci, hande Irem Yigit, Vafa Maharramova, Handan Dincaslan, hanzade Aybüke Unal, Ibrahim Asik, Enver Ozgencil, Emel Cabi Unal
Journal: Journal of Clinical Oncology (2024)

e22002 Background: Pain is one of the most important problems that affects more than half of cancer patients at any stage of the disease and disrupts the quality of life of patients. The aim should be to relieve pain as soon as possible and prevent its recurrence. In this study, we aimed to evaluate the clinical characteristics of our patients who were followed up with a diagnosis of cancer in our clinic and whose pain management was planned in a multidisciplinary manner with the department of Algology. The clinic where the study was conducted is the reference center of a middle income developing country. Therefore, the data obtained will represent the characteristics of developing countries. Methods: In this retrospective descriptive study, patients followed up with diagnosis of cancer at Ankara University Faculty of Medicine, Department of Pediatric Oncology between 2018 and 2023 and consulted to Department of Algology for pain management were included. Patients whose file information could not be accessed from the hospital information system were excluded from the study. Demographic and clinical parameters of the patients were recorded. The data were evaluated with descriptive statistical methods appropriate to distribution. Results: A total of 33 patients, 19 girls and 14 boys, aged between 2.2 and 23.5 (median 14.4) were evaluated in the study. For each case, a median of 2 (1-16) consultations were made. The most frequent cancer diagnosis was bone tumors with 42% (n:14). Nociceptive pain was present in 25 of the patients, nociceptive and neuropathic pain were present together in 8 patients. It was determined that the most commonly used treatment for pain management was paracetamol, which was used in all patients. Other agents used, in order of frequency: Fentanyl in 19 (57.6%) of the patients, NSAID in 13 (39.4%), gabapentin in 9 (27.3%), oxycodone in 12 (36.4%), 7 (3%) 21.2) were tramadol, 4 (12.5%) were morphine, and 1 (3%) was codeine-paracetamol. Intravenous patient-controlled analgesia (PCA) was used in one patient. Side effects were observed in 3 patients. Fentanyl-related constipation was observed in 1 patient, fentanyl-related globe vesicale was observed in 1 patient, and thrombocytopenia was observed in 1 patient due to gabapentin. Conclusions: Pain is an important factor affecting the quality of life and treatment compliance of children with cancer. Therefore, it is important to ensure effective treatment and to raise the awareness of physicians and care providers by keeping it constantly on the agenda especially in developing countries. Prospective studies will be most useful guide for clinicians.
Real-world clinical effectiveness and treatment patterns in the early-stage esophageal/gastroesophageal junction cancer (EC/GEJC) population treated in the community oncology setting in the United States.
Authors: Karthik Ramakrishnan, April Beeks, Adriana Valderrama, Junxin Shi, Gregory Patton, Thomas W. Wilson, Lisa Herms, Sonal Bordia, Sujatha Nallapareddy
Journal: Journal of Clinical Oncology (2024)

e23273 Background: Definitive chemoradiotherapy (dCRT) is the recommended treatment for patients with early-stage EC/GEJC not eligible for surgery. There have been improvements with treatment for esophageal cancer, but the overall 5-year survival rates remain low at approximately 20%. This study examined patient characteristics, current treatment patterns and outcomes with dCRT regimens in the US community oncology setting. Methods: This was a retrospective observational cohort study using structured and unstructured electronic health records data of 300 adult patients with locally advanced/unresectable EC/GEJC who initiated dCRT (index date) within The US Oncology Network between 1 January 2015 and 30 June 2021. Patients were followed through 31 December 2022, last patient record or death, whichever occurred first. Descriptive analyses were conducted to evaluate patient and treatment characteristics. Kaplan-Meier methods were used to assess overall survival (OS) and real-world event-free survival (EFS) from index date. Results: Median age at index was 73 years; three-fourths of patients were male (74.3%), and three-fourths were Caucasian (73.7%). Stage III was the most common stage at initial diagnosis, followed by stage II and stage IVA (55.7%, 34.7%, and 5.3% respectively). The majority of the initial tumor location at diagnosis was esophageal (70.7%) whereas 29.3% were GEJ. Most patients had a baseline ECOG score of 0-1 (63.3%). Median (IQR) follow-up time to death or censor was 10.5 (4.0, 21.0) months from index. The most common initial regimen received was carboplatin+paclitaxel (87%), followed by cisplatin+fluorouracil (9%). Almost all patients received chemoradiotherapy concurrently (99.7%). Median radiation dose was 5040 cGy. Median duration of index treatment was 1.4 months. One-fifth of patients went on to receive a second treatment (21.7%). One-half of patients died before the end of the study observation period (53.7%), and 66% of patients experienced a clinical event (progression, locoregional recurrence, metastatic recurrence or death). Median (95% CI) OS and EFS were 18.1 (13.3, 21.8) and 8.9 (7.7, 10.6) months, respectively. Conclusions: Our study showed that patients mostly received carboplatin+paclitaxel as chemotherapy and did not receive further lines of treatments. Over 60% of patients experienced disease progression with a median survival of a year and a half. These clinical outcomes are poor for early esophageal cancer and support the development of more effective therapies to improve outcomes.
Association between congenital heart disease and cancer: A meta-analysis of 30 million patients.
Authors: Nitya Batra, Vikash Jaiswal, Atulya Aman Khosla, Novonil Deb, Ananya Vadhera, Muhammad Hanif, Aanchal Sawhney, Maha Hameed, Akash Jaiswal, Daniel Ezekwudo, Ishmael A. Jaiyesimi
Journal: Journal of Clinical Oncology (2024)

10568 Background: Birth defects have been associated with increased cancer risk; however, the association between congenital heart disease (CHD) and cancer risk has not been well established with limited and conflicting literature till date. Children afflicted with CHD possess multiple risk factors for oncogenesis, such as chromosomal and genetic abnormalities, ionising radiation exposure during cardiac imaging and interventions, chronic hypoxia and debility. We sought to evaluate the relationship between CHD and cancer risk and its various subtypes. Methods: We performed a systematic literature search on PubMed, EMBASE, and Scopus for relevant articles from inception until February 4th, 2023. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effects model, and a p-value of &lt;0.05 was considered statistically significant. Results: A total of 5 studies with 30,437,431 patients (CHD group=213,229, and non-CHD group = 30,224,202) were involved in the analysis. Mean age of patients with CHD and non CHD was 48.4 and 51.3 years. The pooled analysis revealed that patients with CHD had a higher risk of skin cancer (OR, 1.16(95%CI: 1.10-1.24), p&lt;0.00001), and thyroid cancer (OR, 1.47(95%CI: 1.20-1.80), p&lt;0.001) compared with non-CHD patients. However, leukemia (OR, 0.74(95%CI: 0.22-2.48), p=0.62), gastrointestinal cancer (OR, 1.50(95%CI: 0.79-2.87), p=0.22), central nervous systems tumor (OR, 1.18(95%CI: 0.74-1.88), p=0.48), respiratory system cancer (OR, 0.94(95%CI: 0.67-1.30), p=0.69), breast cancer (OR, 95%CI: 0.96-1.48), p=0.87, genitourinary system cancer (OR, 1.06(95%CI: 0.73-1.54), p=0.76), and musculoskeletal cancer (OR, 1.40(95%CI: 0.92-2.41), p=0.12) was comparable between CHD and non-CHD groups of patients. Conclusions: Our findings indicate that CHD patients are at higher risk of thyroid and skin cancer compared with non-CHD patients; however, no such association with other cancers was observed. The implications of these results extend to the delineation of subsequent research, and the results underscore the necessity for further exploration into the underlying pathophysiological mechanisms. Potential implications include the establishment of enhanced surveillance and screening protocols to protect this vulnerable patient group. [Table: see text]
Statewide burden of cancer attributable to alcohol use in the United States in the last three decades, projections of deaths to 2040: A benchmarking study.
Authors: Geethika Potluri, Sri Usha Jeevani Obulareddy, Himanshu Bharatkumar Koyani, Dhruvkumar Gadhiya, Keethanshan Markandu, Kavya Maddineni, Victor O Adedara, Anusha Parisapogu, Hardik Dineshbhai Desai, Rushin Patel, Ummul Barakat Zakia, Colleen Bramwell
Journal: Journal of Clinical Oncology (2024)

10575 Background: Cancer stands as the 2nd leading cause of deaths and disability in the United States (US), and among the numerous contributing factors, modifiable risk factors play a significant role in exacerbating this burden. Within the spectrum of cancers, alcohol consumption ranks as the second leading attributable cause of death, as per the Global Burden of Disease Cancer Attributable Risk Factor Study. Methods: Employing the GBD protocol, we conducted an estimation of deaths, disability-adjusted life years (DALYs) attributable to cancer caused by alcohol consumption in the US. This comprehensive analysis was stratified by age, gender, year, and geographical location throughout the US, from 1990 to 2019. To project future trends, we utilized time-series regression techniques to forecast deaths until the year 2040. Results: The total number of cancer-related deaths in the US surged from 19,898 (95%UI: 17,791-22,149) in 1990 to 34,455 (30,542-38,388) in 2019. Concurrently, DALYs increased from 532,533 (480,249-586,646) in 1990 to 854,351 (764,549-949,378) in 2019, and YLLs rose from 501,639 (452,446- 554,400) in 1990 to 802,493 (717,123-891,789) in 2019. The highest annual percentage change (APC) in ASR for mortality was observed in West Virginia, with a 32% increase, followed by Tennessee at 27%. Conversely, the District of Columbia witnessed the most significant decrease, with a 30% reduction from 1990 to 2019. In terms of DALYs rates, the highest increases were observed in West Virginia (27%) and Oklahoma (21%). Males bore a greater overall burden compared to females, with an APC in deaths of 97% vs 40% and an APC in DALYs of 87% vs 26%. The highest number of deaths occurred in the 60-64 age group, with 5,228 cases in 2019, while DALYs reached 154,034 in the same year. Projections indicate that the total number of deaths is expected to increase by 49,230 by the year 2040. Conclusions: In 2019, cancer-related deaths attributed to alcohol use represented 4.42% of all cancer mortality cases. From both a public health and clinician perspective, the study's results highlight the urgent need for comprehensive strategies to address the growing burden of cancer associated with alcohol use. Efforts should focus on prevention, early intervention, and support for individuals struggling with alcohol-related cancer risks. [Table: see text]
A fragment-based algorithm for identifying pan-cancer differential methylation markers from cfDNA.
Authors: Xiaowen He, Zhiyu Chen, Jian Li, Chunwei Li, Lingjian Yang, Jingjing Li, Jian Cui, Hefei Li, Wen Xin Liu, Jingjing Hou, Ying Long, Zhichao Liu, Qiumin Wang, Shuang Guo, Qiang Guo, Ping Lan
Journal: Journal of Clinical Oncology (2024)

e22507 Background: Methylation-based sequencing has been developed as a promising approach for Multi-Cancer Early Detection (MCED). Conventionally, cancer-specific methylation markers were identified by comparing paired tumor and adjacent normal tissues using traditional algorithm DSS (Dispersion shrinkage for sequencing data). However, the clinical applicability is limited by the unsatisfactory sensitivity in early-stage disease. Hence, we included blood specific markers derived from paired tissue and blood samples and developed a novel fragment-based algorithm in cfDNA with a better signal to noise ratio (SNR) than DSS to improve the sensitivity of the assay. Methods: A total of 391 plasma samples and 433 tissue samples from 7 cancer types were subjected to whole genome bisulfite sequencing (WGBS) (Table). The proportion of stage I-III and stage IV was 3.5:1 among 7 cancer types. The average sequencing depth was 30X. For each bin, the proportion of fully methylated (M) / un-methylated (U) fragments, defined with methylation level ≥85% / ≤15%, was computed individually. One-sided Wilcoxon rank sum test was employed to test whether cancer cfDNA have significantly (FDR &lt; 0.001) higher proportion of U/M fragments than control cfDNA. Results: To evaluate the performance of fragment-based algorithm in cfDNA, the false positive was assessed by resampling from healthy subjects. The healthy cfDNA were randomly assigned 20 times as pseudo case-control groups of 30 /170. The number of markers among healthy samples was recorded as N False Positive (N FP ), while the number of markers between cancer and healthy samples was recorded as N Positive (N P ). SNR was defined as (N P -N FP )/N FP . We calculated SNR using the fragment-based algorithm and achieved SNR of 135.2 for colorectal cancer, compared to SNR of 2.2 using DSS. The improved SNR was also reproduced in other cancer types. Concordance between plasma and tissue markers was 30.09%-95.92% (median 66.72%) among 7 cancer types, which was related to the proportion of ctDNA for each cancer type. Plasma markers which show weak signals in tissue are defined as blood-specific markers. These markers were enriched in immune-related pathways, suggesting a correlation to the immune response of cancer patients. Conclusions: We developed a novel fragment-based algorithm that achieves much higher SNR than DSS in cfDNA. We also identified blood-specific methylation markers which may improve the sensitivity of early cancer detection in clinical. [Table: see text]