bluuebunny/crossref_metadata_2025_split huggingface dataset:
A retrospective analysis of the concordance of diagnosis predicted by cancer type ID test with pathological or clinical diagnosis with incorporation of treatment response data.
Authors: Xu Yiqing , Kulkarni Ajinkya , Eze-Raphael Chinenye , Toom Sudhamshi 
Published: June 2022

e18684 Background: Carcinoma of unknown primary site (CUP) is a clinical conundrum, where there is metastatic cancer in multiple organs, but the original site of the cancer cannot be determined either by clinical information, or by pathological specification. In most scenarios, clinical and pathological information may narrow down to 2 or 3 most likely primaries; while in some cases, the pathological diagnosis and the clinical picture may not be in concordance. Cancer type ID test, using a panel of 92 genes detectable by RT-PCR test, and bio-informative algorithm, may provide independent information on the cancer of origin. Incorporating this result, as well as the treatment information, one may be able to get closer to the true site of origin for CUP cases. Methods: Patients who have had a Cancer type ID test (ID test) performed and had received systemic treatment were eligible for this study. We analyzed the concordance of ID result of major probability (> 90% probability) with pathology diagnosis, the concordance of ID result of minor probability (6% probability or “cannot exclude with < 5% probability” with pathology diagnosis, and the concordance of ID result of major probability with final clinical diagnosis (incorporating treatment response data, tumor next gene sequencing data, and genetic test data). We also divided cases into groups of differentiation between 2-3 possible primaries, or true CUPs (as shown in the table below). Results: 26 patients were identified. There were 9 males and 17 females. The median age was 65 years old (ranger 37-92). The final clinical diagnoses were GI (upper and lower intestinal) (n = 6), pancreatic (n = 3), cervical (n = 2), lung adeno (n = 2), lung carcinoid (n = 1), sarcoma (n = 1), GYN (n = 2), Head neck (n = 1) and breast (n = 1). 7 cases remained as CUP. Conclusions: Cancer type ID test, with a combination of 90% probability, the 6% probability as well as the “cannot exclude with a less than 5% probability”, may reach 92% concordance with pathological diagnosis. It has the highest prediction in differentiation of 2-3 primaries, especially when one primary involves pancreas. However, the concordance between the clinical diagnosis and the diagnosis rendered by the ID test major prediction is not optimal, and will need further improvement.[Table: see text]
Evaluating the impact of performance status criteria on minority eligibility for oncology clinical trials.
Authors: Bhandari Sudip , Mann Jeremy , Chawla Jitesh , Jain Prerna , Knight Margot , Lagor Charles , Mueller Judith , Raska Paola , Southwick Steve , Whyte Warren 
Published: June 2022

e18701 Background: Restrictive criteria contribute to low enrollment in clinical trials. These criteria can also amplify health disparities by reducing the racial and ethnic diversity of the cohort. Many studies show that minority patients exhibit worse Eastern Cooperative Oncology Group (ECOG) performance status than white patients. Based on clinical trial data, some researchers have hypothesized that relaxing the ECOG criterion in clinical trial criteria could improve the diversity of the cohort. However, little research exists to measure ECOG’s impact on minority eligibility. Using Real-World Data (RWD), we evaluate whether relaxing the ECOG criterion monotonically increases the racial diversity of the cohort in oncology clinical trials. Methods: We used ConcertAI’s database of US oncology Electronic Medical Record (EMR) data, which includes clinical data from CancerLinQ Discovery™. We conducted sensitivity analyses for the inclusion criteria of 16 different clinical trials across multiple cancer indications. For each trial, we created five cohorts based on five different ECOG score upper limits. For example, the first cohort only included patients who had an ECOG of 0, the second cohort included patients with an ECOG of 0 or 1, etc. We then recorded the percentage of non-white patients for the resulting cohorts. We ran simple linear regressions to measure whether the change in the percentage of non-white patients was statistically significant. Results: Relaxation in ECOG status led to no uniform change in the racial diversity of patients across the 16 trials. The limited changes we did observe were not statistically significant. Conclusions: Our findings suggest that improving diversity will require more than just relaxing ECOG restrictions, and a multi-faceted approach may be needed. Future research exploring the relationship between ECOG and diversity should control for potential confounders like age, gender, and comorbidities using multivariable models. Such research needs to also account for patients with unknown race and ECOG, which represented large parts of our study population. Such research could elucidate whether the phenomenon observed in the general population—that minority patients tend to have worse performance status than whites—holds true in the sub-population of oncology patients.[Table: see text]
Impact of COVID-19 on risk of venous thromboembolism (VTE) in cancer patients: A single institution analysis.
Authors: Ananthula Aneesha , Thomas Katharine , Tran Dat , Nguyen Anh , McQueen Amaker Katie Lauren McLemore , Thrash Brandon T , Gibson William , Germain Monique , Mani Shyam , Chapple Andrew G , Subbiah Suki 
Published: June 2022

e18732 Background: Cancer is known to increase the risk of VTE when compared to the non-cancer population. Additionally, SARS-CoV-2 infection has been associated with hypercoagulability and VTE. A study by Patell et al noted similar cumulative incidence of thrombotic events (arterial and venous) in patients hospitalized with COVID-19 with active cancer than those without cancer (14.2% vs 18.2%). Data from the COVID-19 and Cancer Consortium (CCC19) Registry reported incidence of VTE of 7.6% in cancer patients within 90 days of hospitalization for COVID-19. However, it is unknown whether patients with cancer are at significantly higher risk for VTE in the setting of COVID-19 compared to cancer patients without COVID-19. Our study objectives were to: 1) determine the overall incidence of VTE in patients with cancer with and without COVID-19, regardless of hospitalization status; 2) assess the relative risk of VTE due to COVID-19 in cancer patients; 3) examine risk for VTE in cancer patients with COVID-19 based on certain demographic characteristics and comorbidities. Methods: An institutional retrospective cohort analysis was performed from March 1, 2020 through July 31, 2021. 228 patients with COVID-19 and cancer were identified and compared to matched controls without COVID-19 (n = 448) during the same study period based on age, gender, and BMI. Results: Incidence of VTE in cancer patients with COVID-19 was significantly higher than in cancer patients without COVID-19 (11% vs 3.1%) [RR 3.45, 95% CI 1.85-6.67]. There was no significantly increased risk of VTE in cancer patients with COVID-19 based on the following characteristics: non-White race, male gender, diabetes mellitus, hypertension, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and end-stage renal disease receiving dialysis. However, patients with any history of smoking (including current smokers) had increased risk of VTE compared to never-smokers (RR 2.2756, 95% CI 1.0498-4.9326). Conclusions: COVID-19 further increases the risk of VTE in cancer patients, a population with an independent risk factor for VTE at baseline. Whether the increased risk is additive or synergistic is currently unknown. Demographic factors and comorbidities that have been associated with increased severity of COVID-19 in other studies do not appear to significantly increase risk of VTE in cancer patients with COVID-19, with the exception of smoking status (either current or past). Given the impact on morbidity and mortality, further analyses, including with larger datasets, are warranted.
Measuring the great objective: Have we transferred the increase in overall survival in stage IV non-small cell lung cancer from clinical trials to clinical practice?
Authors: Sanchez Juan Cristobal , Nuñez García Beatriz , Blanco Mariola , Calvo Virginia , Cantos Sanchez de Ibarguren Blanca , Mendez Miriam , Aguado Ramon , Ramos-Vegue Arturo Jose , Royuela Ana , Provencio-Pulla Mariano 
Published: June 2022

e18734 Background: In the last five years, different immunotherapy (IO) clinical trials have improved overall survival (OS) for stage IV non-small cell lung cancer (NSCLC) without driver mutation. However, it is necessary to check whether outcomes of clinical trials are reproduced in the general population, the true objective of any scientific advance. Methods: We conducted a retrospective observational study selecting all patients with stage IV NSCLC without driver mutation treated in the Medical Oncology Department at Puerta de Hierro University Hospital between 2016 and 2019. Data cut off was June 30, 2021. Our goal was to evaluate treatment changes for NSCLC in clinical practice in our institution with OS in the real-world as the main outcome, in addition to assessing quality of care. Results: Between 2016 and 2019, 317 patients with stage IV NSCLC were diagnosed, 260 without driver mutation and 189 of them received systemic treatment. We observed a higher proportion of stage IVB patients in 2018 and 2019 compared to 2016 and 2017. A progressive greater use of IO was observed, except for a small decrease in 2019 compared to 2018. At the date of analysis, 77.8% of patients had died. With a median follow-up of 40.8 months, we observed a gradual increase in OS, with medians of 12.3, 13.6, and 18.9 months for patients diagnosed in 2016, 2017, and 2018, respectively, with a decrease to 10.4 months for patients diagnosed in 2019. Survival rates over time show the same trend. IO (any line) was significantly associated with a reduced risk of death: HR 0.35 (95% CI: 0.23 - 0.58) in multivariate analysis. The deterioration of the results of the patients diagnosed in 2019 is manifested in the median survival and in the survival rates at different points from 6 months onwards, which should correspond to the excess mortality in the year 2020 in our studied population. Conclusions: Our study shows that IO reduced risk of death: HR 0.35 (95% CI: 0.23 - 0.58) in stage IV NSCLC, observing an increase in overall survival from a median of 12.3 to 18.9 months for patients diagnosed in 2016 and 2018, suggesting that the progressive use of IO for NSCLC in the years 2016, 2017 and 2018 has transferred the benefit observed in clinical trials to the general population. The deterioration of outcomes for patients diagnosed in 2019, with a median OS of 10.4 months and decreased survival at 6, 12 and 18 months, could suggest the negative impact and excess mortality in the pandemic year 2020.[Table: see text]
Ramifications and healthcare costs of Clostridioides difficile infections in hospitalized patients with solid tumors.
Authors: Tarar Zahid , Au Pak Ho , Nwabara Kelechi , Franco Diana , Egwom Peter , Gvazava Nanuli , Saleh Mohammad , Ghous Ghulam 
Published: June 2022

e18801 Background: Clostridioides difficile infection (CDI) is notorious for its perilous effect on frail patients, but its assault is even more so threatening on cancer patients as they are more prone to CDI due to damage to intestinal mucosa by chemotherapy agents and weak immune system, hence higher risk of getting affected from hospital-acquired infections. Here we analyze National inpatient sample database (NIS) of hospitalized patients with solid tumors to find out aftermath of CDI in this particular patient population. Methods: We used NIS database from year 2019 and recruited all patients admitted with C. diff colitis with underline solid tumors with or without metastatic disease. We used international classification of disease,10th revision (ICD-10) codes to identify these patients. Our outcomes of interest were all cause inpatient mortality, acute kidney injury (AKI), sepsis, ICU admission, pressor use and hospital resource utilization including mean length of stay (LOS) and mean total charges. Using STATA 17, we performed the multivariate regression analysis. Results: A total of 15,161 (1.41%) hospitalizations due to principal diagnosis of C. diff Colitis were recorded in solid tumor patients in year 2019. Patients with history of solid tumors who were admitted with C. diff colitis had higher adjusted odds of all-cause in-hospital mortality (AOR 1.23, 95% CI1.08-1.41, P 0.002) compared to patients without underline solid tumor. These patients also had higher odds of sepsis (AOR 2.22, 95% CI 1.89-2.59, P < 0.001), AKI (AOR 1.91, 95% CI 1.73-2.10, P < 0.001), ICU admission (AOR 1.66, 95% CI 1.39-1.97, P < 0.001) and pressors use (AOR 1.82, 95% CI 1.38-2.40, P < 0.001). Patients with underline solid tumors who developed C. diff colitis had increased mean LOS (AOR 3.88, 95% CI 3.41-4.34, P < 0.001). These patients also incurred more hospital charges (Co-efficient 33836$, 95% CI 25907$-41766$, p < 0.001). [Table]. Conclusions: Patients with solid tumors admitted with CDI have an increased risk of sepsis, AKI, ICU admission and in-hospital mortality. They also have a significantly longer duration of hospital stay; hence higher cost of care. There is a dire need for awareness regarding strict contact precautions, hand hygiene, effective environmental cleaning, minimizing antibiotics use/adherence to antibiotic stewardship programs, using prophylactic vancomycin where indicated, avoidance of unnecessary hospital visits utilizing telehealth, etc. and aggressive management of CDI in patients admitted to hospital with solid tumors.[Table: see text]
Dissection of the expressed actionable fusions’ repertoire in solid tumors tested serially in the clinical setting across 14 cancer types.
Authors: Lopez-Diaz Fernando J. , Schell Rachel , Duong Chaugiang , Rivera Steven , Funari Vincent Anthony 
Published: June 2022

e18804 Background: More frequently, select gene fusions have been tested in clinical practice as more approvals of very effective therapies targeting oncogenic chimeric fusion proteins. Large studies based on DNA-based NGS testing alongside clinical trials have established the prevalence of clinically actionable gene fusions such as NTRK1/2/3. However, much less is known about the broader repertoire and prevalence of bonafide expressed gene fusions. Methods: 6009 tumors across 14 cancer types were tested in our clinical laboratory between January and October 2021. Enrichment was performed using a custom hybridization-based capture after RNA to cDNA conversion with custom designed probes targeting > 1104 different genes and enriched for 2230 specific RNA fusions to maximize sensitivity and breadth before sequencing ̃50 million 150x150 reads/sample on a NovaSeq 6000. Data was deidentified and aggregated according an approved IRB. Statistical significance was calculated by Fisher’s exact test. Results: We found that 37% of tumors tested carry > 1 expressed chimeric transcript and that 7.2% of tumors (n = 431) express a gene fusion involving one of 19 actionable gene families/pathways targeted by an approved therapy. The most frequent involved FGFR1/2/3/4 (15%), ALK (14%), NTRK1/2/3 (12%), BRAF, ERBB2, RET and MET (6% each), RAS/RAF/MAPK and CDK4/6 pathway (5%). These fusions imply intra- and inter-chromosomal translocations on all chromosomes, especially on chromosomes 1, 3, 6, 7, 11, 12 and 17. NTRK1/2/3 fusions prevalence (0.9%) is significantly higher (p = 1.1e-10) than the 0.3% reported on a recent study from a large dataset (296K samples) based on DNA-sequencing testing (1). Moreover, we found that 32% of the NTRK partners were unique vs. 10% (p = 6.5e-08) from the Westphalen et al. study (1). 14 of 25 unique NTRK partners have not been described on large datasets (1) and only 3 have been reported on the literature as NTRK partners. Among them, we identified the hypoxia-induced neovascularization gene HIF1A, as a novel in frame 3’ fusion partner of NTRK3 [t(15;14)(15q25.3; 14q23.1). Finally, NTRK fusions were detected across 14 cancer types with higher frequency on brain tumors (17%), followed by lung cancers, colorectal and head and neck cancer (13% each) and sarcomas (12%). Conclusions: Gene fusions involving common actionable genes showed a high prevalence in the clinical setting. This study confirms that the number and breadth of gene fusions can present with common actionable information in > 7% of clinical cases. We report here 14 new unique NTRK partners. Despite a 50 times smaller dataset, 3-fold more actionable expressed NTRK fusions involving novel partners were detected with a targeted RNA based hybridization approach in lieu of DNA based testing supporting the benefit of this strategy. Overexpression and translation can be confirmed only by this approach.
Effect of delayed consolidation durvalumab and timing of treatment on survival outcomes in patients (pts) with unresectable stage III non-small cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT).
Authors: Stevens Samuel Xavier , Nindra Udit , Shahnam Adel , Bray Victoria Jane , Yip Po Yee , Adam Tamiem , Lee Jenny HJ , Boyer Michael J. , Nagrial Adnan , Kao Steven Chuan-Hao 
Published: June 2022

e18809 Background: Consolidation treatment with durvalumab following CRT is now standard of care for pts with unresectable stage III NSCLC. In PACIFIC, durvalumab was administered within 42 days of completing CRT. There has also been recent interest in whether the time-of-day immunotherapy is given impacts on outcomes. In practice, many pts experience delays to consolidation immunotherapy, and the timing of infusions is variable. We investigated the effect of treatment delays and time-of-treatment on survival outcomes in a real-world setting. Materials & Methods: A retrospective observational study was conducted with patients treated with consolidation durvalumab following concurrent platinum-based CRT for unresectable stage III NSCLC in 6 centres across Sydney, Australia between January 2018 and September 2021. The primary outcomes were overall survival (OS) and progression-free survival (PFS) based on RECIST v1.1, from completion of radiotherapy. We collected treatment initiation and completion dates as well the administration time of durvalumab. In the time-of-treatment analysis, pts were stratified into median time of treatment either before or after 12.00pm. Survival was estimated using Kaplan-Meier and Cox-proportional hazard models. Results: 145 pts were included in the study. Median age was 67 years. 62.3% of pts were male, 84.9% were smokers, and 57.5% had adenocarcinoma. The median time between completion of CRT and commencement of durvalumab was 59 days (11-187 days). 71.2% (n = 102) of pts experienced a treatment delay. Over a median follow-up of 18.9 months, median PFS was 33.9 months in pts treated within 42 days of CRT and 25.6 months in pts treated beyond 42 days of CRT (HR 0.97; 95% CI 0.46-2.06; p = 0.815). Median OS was not reached in either group but no difference in OS was observed in the two cohorts (HR 1.07; 95% CI 0.39-2.96; p = 0.88). Median timing of treatment did not affect outcomes for either PFS (HR 1.07; 95% CI 0.50-1.71; p = 0.80) or OS (HR 1.01; 95% CI 0.44-2.31; p = 0.91). Conclusions: No difference in survival outcomes was seen between patients who had received durvalumab 42 days after CRT compared to within 42 days. The median timing of treatment did not appear to impact outcomes in our cohort.
Financial toxicity among patients with breast cancer in a publically funded health care system in Brazil.
Authors: Arevalo Andrea , Nunes Joao Soares , Nakakogue Tabatha , Figueiredo Alexandre Luders , Somensi Eduardo de Souza , Hauki Mariana Cararo , Weffort Marcos Daniel 
Published: June 2022

e18818 Background: The concept of financial toxicity (FT) has been used to describe the unanticipated economic damage potentially caused by cancer treatment. Currently, it has been associated with decreased health-related quality of life (QoL), treatment nonadherence and increased risk of mortality. Even in publicly funded environments as Brazilian Unified National Health System, factor such as income loss or out-of-pocket costs could become an issue for cancer care. The aim of this study was to examine the FT related to the breast cancer diagnosis and treatments in a public Brazilian tertiary hospital through Comprehensive Score for Financial Toxicity (COST) instrument. The COST is a 12-item survey scored from 0 to 44, with lower scores reflecting worse financial well-being. Methods: This cross-sectional study was conducted among breast cancer patients in active treatment for at least 6 months attending medical oncology out-patient department. Socio-demographic, clinical characteristics and a simplified assessment of QoL were collected as well as responses to COST questionnaire. Descriptive statistic and analysis of correlations between quantitative variables and scores of QoL and COST were performed. Results: A total of 100 female patients were included with median age of 53 years old. The mean time from initial diagnosis was of 49.6 months and clinical stage IV represented 46% of all cases. Prior to the cancer treatment, 48 (48%) of the patients had their own job as a main source of income. However, after the cancer diagnosis, only 9 (9%) patients keep working, 36 (36%) needed to use savings and 29 (29%) applied for a bank loan. To adjust their finances, 66 (66%) patients reduced spending on leisure. The median COST score was 18.5 (ranged from 4 to 41). According to the age, patients with ≤ 45 years old were at higher risk of suffering FT (p = 0.01). There was also an association between the COST score and QoL since the higher the FT, the lower the QoL (p < 0.001). Conclusions: Patients with breast cancer are at risk of losing their work capacity, become financially dependent of other, and suffering a reduction in QoL as a result of FT. Mostly younger patients are at greater risk of FT. Despite a universal health-model, this study highlights a substantial proportion of patients who experienced FT. Therefore, further studies confirming these findings in larger groups are warranted to develop better strategies and policies to mitigate this form of toxicity.