bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generative adversarial neural networks augment marker and pathway analysis of treatment resistant HPV+ head and neck squamous cell carcinoma.
Authors: Waters Michael , Inkman Matthew , Andruska Neal , Brenneman Randall , Markovina Stephanie Subasic , Schwarz Julie Kristina , Zhang Jin 
Published: June 2022

e18059 Background: Biological behaviors of cancers are extremely complex and governed via nonlinear interplay of thousands of genes. This complexity has become a major hurdle to generating mechanistic conclusions in rare clinical scenarios, such as treatment resistant HPV+ head and neck squamous cell carcinoma, when observations are limited. Recently, data augmentation algorithms have served to increase the number and diversity of training observations while preserving the underlying structure and nonlinear relationships of data features. Deep learning techniques such as generative adversarial neural networks (GANs) have shown promise as robust tools for data augmentation of nonimage data. This study aims to evaluate the utility of employing separate GANs to highlight gene expression differences between treatment sensitive (TS) vs treatment resistant (TR) HPV+ head and neck squamous cell carcinoma. Methods: We performed RNAseq on 17 patients with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). We defined TR patients as those with locally advanced OPSCC at presentation, who rapidly recurred following receipt of standard of care therapy (n = 11). In most cases, patients failed to respond to salvage therapies and rapidly died. In contrast, we defined TS patients as those with locally advanced OPSCC at presentation, who received standard of care therapy, and were followed for 5 years without any evidence of recurrence (n = 6). These two cohorts were used to train two separate GANs, which synthesized 500 robust synthetic samples of each phenotype for downstream analysis. Results: Analysis of 17 samples yielded less than 100 differentially expressed (DE) genes passing FDR cutoffs, inhibiting pathway enrichment analysis (PAE). DE testing between synthetic samples yielded 1196 DE genes. Validating our deep learning approach, these genes belong to coherent pathways as determined by PAE. Namely, the VEGFA-VEGFR2 pathway was strongly enriched in the TR population (p = 1.5 x 10-4). Further, the NKT cell signature (p = 3.0x10-62), and the gene library of T-cell receptor induction of apoptosis (p = 5.4 x 10-9), was enriched in the TS population. Lastly, to validate the experimental method, DE testing on GAN augmented cohorts of renal papillary vs renal clear cell samples from The Cancer Genome Atlas, trained on 10 samples per condition, reliably predicted DE genes when comparing the full cohort of renal papillary n = 534 vs renal clear cell n = 295 samples, with an accuracy of 93% and F1 score of 88%. Conclusions: To our knowledge this is the first study to utilize separate GANs to augment structural gene expression changes occurring in rare clinical scenarios such as treatment resistant HPV+ OPSCC. Utilizing this method uncovers changes in angiogenesis and T-cell function between treatment sensitive and resistant HPV+ OPSCC.
Etiology of oral candidiasis in patients with oropharyngeal cancer.
Authors: Ulianova Yulia V. , Kutsevalova Olga Yu. , Pustovaya Irina V. , Volkova Viktoriya L. , Bauzhadze Mamuka V. , Chertova Natalia A. , Goncharova Elena G. , Maldonado Mary L. 
Published: June 2022

e18068 Background: The purpose of this study was to assess the etiology of oral candidiasis in patients with oropharyngeal cancer as potential causative agents of invasive candidiasis and to analyze in vitro activity of isolates of Candida fungi to caspofungin, fluconazole and voriconazole. Methods: Isolates were obtained in a prospective study from the oral mucosa of patients with oropharyngeal cancer in 2020-2021. Identification of Candida fungi was performed using MALDI-TOF MS. Result of activity of isolates to caspofungin, fluconazole and voriconazole after 24 hours of incubation were registered according to CLSI M60-ED2:2020 (Performance Standards for Antifungal Susceptibility Testing of Yeasts). Results: 45 patients aged 30-85 years were examined. 92 isolates of Candida fungi were obtained: C. albicans 31.5% (29) and Candida non albicans 68.5% (63). Candida non albicans included: C.parapsilosis 30.2% (19), C.glabrata 28.6% (18), C.krusei 19.0% (12), C.tropicalis 15.9% (10), C.guilliermondii 6.3% (4). Candida carriage on the oral mucosa was noted in 62.2% of patients in the first days of hospitalization, with a predominance of C. albicans 42.8% compared with 32.1% after chemotherapy (p = 0.003) and 25.0% after antibiotic therapy. The distribution of species varied depending on the age of patients. The table presents comparative activity of caspofungin, fluconazole and voriconazole (susceptible (S), moderately resistant (I), resistant (R)) in % to Candida spp. High sensitivity to caspofungin was noted for both C.аlbicans and Candida non albicans. Voriconazole was characterized by lower sensitivity and natural resistance in C.glabrata which makes it less suitable for empirical therapy, as well as fluconazole. Conclusions: Candida non albicans (68.5%) were predominant in the oral candidiasis etiology in patients with oropharyngeal cancer, which was probably due to the use of azole antimycotics for prevention and empirical therapy. Reduced activity to voriconazole and fluconazole was observed in the dominant isolates, given the natural resistance of C. krusei to fluconazole and C. glabrata to voriconazole. Acquired azole resistance was noted for C. parapsilosis and C. albicans. The pathogen type should be determined in all cases of invasive candidiasis to exclude natural resistance and sensitivity to azoles before starting therapy.[Table: see text]
Selective treatment de-intensification with reduced-dose radiation and omitted concurrent chemotherapy guided by response to induction chemotherapy in HPV-associated oropharyngeal squamous cell carcinoma: A single-arm, phase II trial (IChoice-01).
Authors: Lu Xueguan , Xu Tingting , Zhou Xin , Shen Chunying , Zhang Qixian , He Xiayun , Ou Xiaoming , Ying Hongmei , Wang Yu , Ji Qinghai , Hu Chaosu 
Published: June 2022

e18069 Background: De-intensification in chemoradiation provides a strategy to optimize the trade-off between treatment efficacy and toxicities in HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). However, the failure of RTOG 1016 and De-ESCALaTE indicated the pitfall of de-escalation in an unselective population and the importance of patient selection for future study design. Induction chemotherapy (IC), as a potential biomarker, has been adopted in several trials to screen candidates for de-intensified treatment based on its tumor response. In present trial, we investigated the feasibility of selectively de-intensified chemoradiotherapy by reducing radiation dose and omitting concurrent chemotherapy guided by response to IC. Methods: From Jan 2019 to July 2021, 48 patients with p16 positive OPSCC, T1-2/N1-3M0 (excluding T1N1M0 patients with single and≤3cm lymph node) or T3-4N0-3M0 according to the UICC/AJCC 8th staging system were enrolled. All of them received two cycles of IC with cisplatin and docetaxel. Those with major response to IC (defined as cCR or ≥50% cPR of both primary site and lymph nodes) received de-intensified treatment with intensity modulated radiation therapy (IMRT) alone with 60Gy to high-risk and 54Gy to low-risk regions (Di cohort). Those with less than major response were given standard chemoradiotherapy with 70Gy to both primary tumor and positive lymph nodes, 63Gy to high-risk and 56Gy to low-risk regions, concurrently with two cycles of cisplatin (St cohort). The primary endpoint was 2-year progression-free survival (PFS). Results: 26/48 (54.2%) patients entered Di cohort while other 22/48 (45.8%) patients entered St cohort. With a median follow-up time of 20.5 months (2.8-36.7months), 3 deaths (1 in Di cohort and 2 in St cohort), 5 loco-regional recurrence (1 in Di cohort and 4 in St cohort) and 6 distant metastases (1 in Di cohort and 5 in St cohort) were documented. The 2-year PFS rates for Di and St cohort were 100% and 60.0% (P = 0.002) with overall survival (OS) rates of 100% and 83.1% (P = 0.062), loco-regional recurrence-free survival (LRFS) rates of 100% and 77.0% (P = 0.035), metastasis-free survival (MFS) rates of 100% and 66.8% (P = 0.011), respectively. Conclusions: For major responders to IC, reduced-dose radiation with omitted concurrent chemotherapy yielded good survival results. In comparison, patients resistant to IC showed poor prognosis even under standard-dose chemoradiotherapy, calling for treatment intensification or development of novel therapeutic agents. Selective de-intensification of chemoradiation guided by response to IC is promising in HPV-associated OPSCC and warrants further evaluation in future studies. Clinical trial information: NCT04012502.
FAST-FNA molecular diagnostic assay facilitates rapid diagnosis and ntrk biomarker testing of salivary gland tumors.
Authors: Pai Sara I. , Oh Juhyun , Yoo Tae Yeon , Faquin William C , Carlson Jonathan C.T. , Saal Talia M. , Deschler Daniel G. , Weissleder Ralph 
Published: June 2022

e18089 Background: Primary epithelial salivary gland tumors (SGTs)are classified into 31 tumor types. Diagnosing SGTs through fine needle aspiration (FNA) biopsies is challenging due to the overlapping cytomorphologic features between benign and malignant tumors. In this study, we developed an innovative, multiplexed cycling technology which allows for the rapid cellular analyses of single cells obtained from FNA which can facilitate the rapid molecular analyses and diagnosis of SGTs. Methods: Antibodies against 29 cell surface markers associated with 7 SGT subtypes were validated and chemically modified via custom linker–bio-orthogonal quencher probes (FAST). Single cell homogenates and a FNA sample set representing 7 SGT subtypes were profiled by FAST cyclic staining, imaging, and automated computational analysis. A prediction model was generated utilizing a training set of 151,926 single cells obtained from primary SGTs (N = 26) and validated on a separate cohort of SGTs (N = 30). Companion biomarker testing, such as NTRK, was also assessed with the FAST technology. Results: The customized FAST-FNA SGT molecular diagnostic and biomarker panel was validated on human cell lines and specificity confirmed by both flow cytometry and clinical immunohistochemical staining on primary SGTs. The FAST molecular diagnostic assay was able to distinguish between benign and malignant SGTs with an accuracy of 0.86 for single-cell suspension samples and 0.88 for FNA samples. Profiling of multiple markers as compared to a single tumor marker increased the diagnostic accuracy of the SGTs, 0.82 as compared to 0.65-0.74, respectively. The results of the assay were highly reproducible and independent of the cell number sampled. NTRK expression in SGTs was also assessed by the FAST assay within hours, highlighting the potential therapeutic application of this technology. Conclusions: High dimensional single-cell profiling and molecular diagnostic testing on FNA samples are feasible at relatively low cost and as a rapid test. Application of the novel multiplexed single cell technology improves the diagnostic accuracy of SGT biopsy and facilitates multiplex biomarker testing from FNA samples. The customizable and modular FAST-FNA approach has relevance to multiple pathologies and organ systems where cytologic samples are often scarce and/or indeterminate resulting in improved diagnostic workflows and timely therapeutic clinical decision making.
Disparities in timely treatment among lung cancer patients.
Authors: Chhabra Jatin , Ray Herman , Derkach Sergii , Thompson David , Whyte Warren 
Published: June 2022

e18515 Background: NSCLC is the leading cause of cancer-related deaths in the US. There are no federal standardized guidelines regarding timely treatment (TT) of NSCLC care and little is known regarding the sociodemographic differences in TT of anticancer therapies among NSCLC patients. This is particularly notable among Black Americans, who are less likely to receive lung cancer screening, more likely to be diagnosed with advanced or metastatic NSCLCL, and less likely to receive NCCN-concordant targeted therapy relative to their white counterparts. The objective of this retrospective study is to assess racial differences in TT and related outcomes among patients with advanced or metastatic NSCLC (aNSCLC). Methods: We identified 3,603 patients from ConcertAI’s Real-world data (RWD) sources, including CancerLinQ Electronic Medical Records. Patient demographics included: a) aged 18 to 64 years; b) confirmed diagnosis of aNSCLC between January 1, 2010, and December 31, 2019; and c) self-identify as White or African American. For this study the primary endpoint was receipt of TT, defined as start of systemic therapy within 30 days after diagnosis of aNSCLC. Logistic regression was leveraged to obtain adjusted odds ratios of comparisons between White and Black American populations on receipt of TT, controlling for demographic and baseline characteristics such as type of setting, ECOG score and smoking status. Results: Descriptive analyses revealed 79.1% of Black aNSCLC patients did not receive TT, as compared to 71.4% of White aNSCLC patients. When controlling for associated confounding factors, Black aNSCLC patients had a 21.4% less chance of receiving TT as compared to White patients, and the same was evident from the predicted probabilities of TT for Black vs. White aNSCLC patients. When evaluating institutional setting type, 76.1% of community hospitals provided TT vs. 61.3% of academic centers. Conclusions: This real-world study shows Black aNSCLC patients were associated with treatment delay. While present findings suggest improving access to effective screening and timely access to NCCN-concordant targeted therapies may be used as a means through which to lessen NSCLC disparities, further investigation is required to assess how it may improve overall outcomes for minorities. [Table: see text]
Patient-reported reasons for no-shows to screening mammogram appointments among African American women.
Authors: Hensing Whitney L , Tao Yu , Park Chaelee , Redding Dori , Arb Teresa , Clark Pechaz , White Stephanie , Thompson Tess , Ademuyiwa Foluso Olabisi 
Published: June 2022

e18534 Background: Mammography screening significantly reduces breast-cancer related mortality; however, many women fail to undergo screening as recommended by national guidelines. No-shows are responsible for a significant proportion of delayed or missed cancer screening exams. Further, no-shows disproportionately affect underserved and minority populations. We previously identified a high no-show rate for screening mammograms among patients seeking care our institution. African American (AA) women were almost three times more likely to no-show than non-Hispanic white women. The racial disparity in no-shows persisted after adjustment for socioeconomic factors. The objective of this survey study was to identify reasons for missed mammogram screening appointments among AA women. Methods: We conducted a survey (via mail or telephone) of AA women who missed their screening mammogram appointment in summer 2021. Using a structured survey instrument, we collected information on patient-specific and health service barriers. Patient-specific barriers included procedure-related concerns (e.g., concern about discomfort), cognitive-emotional factors (e.g., fear of finding cancer), and changes in health status. Health service barriers included logistical factors (e.g., transportation), cost (e.g., lack of insurance) and scheduling problems (e.g., forgot about appointment or scheduled at an inconvenient time). Here we describe the most common reasons for missed appointments and compared women who reported patient-specific versus health service barriers. Results: 255 women who no-showed for their appointment were contacted and 91 participated in the study survey (35.6% response rate). Most respondents (90%) attributed their no-show to at least one of the listed barriers. Nineteen (7.5%) attributed their no-show to COVID-19, but only 1 person reported this as their only barrier. Scheduling issues were the most commonly reported barriers (57.8%), followed by transportation (38.9%). Three-quarters of respondents reported health service barriers, while only 40.7% reported patient-related barriers. The most common patient-related barriers were cognitive-emotional (25%), changes in health status (20.9%) and procedure-related concerns (15.6%). The majority of respondents (82.6%) were interested in rescheduling their mammogram. Conclusions: Most appointment no-shows among surveyed AA women resulted from potentially preventable scheduling and transportation issues. Relatively few respondents reported cognitive-emotional or procedure-related concerns. Further, the majority of respondents were interested in rescheduling their mammogram; which suggests that these women remain motivated to undergo breast cancer screening. Programs which address preventable health-service related issues may help these women keep their appointments.
Estimating patient demand for oncologists in the United States using Google trends.
Authors: Waris Shanawar , Raiker Rahul , Siva Nanda , Koirala Monika , Pakhchanian Haig , Boustany Osama , Khalid Ahmed A. 
Published: June 2022

e18535 Background: Cancer accounts for a massive burden of global disease, healthcare expenditure, and is one of the leading causes of death worldwide, accounting for approximately 1 in 6 deaths. As both the incidence and prevalence of cancer continue to increase, along with the percentage of the population over the age of 65, it is important to understand patient demand for oncologists. Previous studies have predicted a shortage of over two thousand oncologists by 2025. The inconsistencies between supply and demand for oncologists require analysis and supervision to identify potential gaps in oncological care and fulfill patient demand for quality care. Methods: The average relative search volume (RSV) for the term “oncologist” was determined by analyzing Google Trends from 2004-2019 for each state. The oncologist per capita values were computed by taking the number of oncologists per state and then dividing by the corresponding 2019 Census estimates. The RSV values were then divided by per capita values to quantify demand index and standardized to generate a relative demand index (RDI). A spearman’s rho correlation test was also conducted to assess the relationship between RDI and overall 2019 state health rankings as conducted by the America’s Health Rankings group. Results: The states with highest RSV was New Jersey (100), Florida/Tennessee (98), and Connecticut (97), while the lowest RSV were Oregon (53), Alaska (44), and Vermont (41). The RDI for oncologists was greatest in Idaho (100), Mississippi (86), and Arkansas (77) while the lowest were for Vermont (15), Massachusetts (14), and District of Columbia (8). Spearman’s rho test revealed a strong negative relationship between RDI and overall state health ranking that was statistically significant (rs= -0.6363, p < 0.001). Conclusions: These trends may give us a preliminary idea of states that have unmet healthcare needs in oncology. Further studies are warranted.
Profile and outcomes of patients with subsequent ovarian cancer diagnosis following a prior malignancy in the United States.
Authors: Akinyemi Oluwasegun , Abodunrin Faith , Andine Tsion F , Akinwumi Bolarinwa , Akinyemi Irene , Ojo Ademola , Lipscombe Christina , Silberstein Peter T. 
Published: June 2022

e18541 Background: The relationship between a subsequent ovarian cancer and a prior malignancy is complex with possible etiological, genetic, and therapeutic implications. Little is known about the epidemiological and clinical profile of this category of patients. The aim of the present study is to determine the factors associated with the development of ovarian cancer as a subsequent malignancy after a prior malignancy from another organ and determinants of improved survival in these women. Methods: We utilized the SEER 18 Registry 1975-2016 to conduct a retrospective analysis of women who developed a second primary ovarian malignancy following a prior cancer diagnosis. The outcome of interest was the latency interval between the initial primary malignancy diagnosis and a subsequent ovarian cancer diagnosis. Utilizing the cox regression model, we determined the factors associated with the overall survival of these women. Results: There were 10, 800 women who subsequently developed ovarian cancers following a prior malignancy. The commonest prior malignancies were breast cancers (38.2%), endometrial cancers (23.7%), and colorectal cancers (9.5%). The latency interval from developing a subsequent ovarian malignancy was 6.8±6.3 yrs. (Breast cancers) and 0.6 ± 2.5 yrs. (Endometrial cancers). A prior surgical treatment (OR = 1.19; 95% CI 1.02-1.40) or radiotherapy (OR = 1.34, 95% CI 1.21-1.49) in the initial primary malignancy is associated with a > 5years development of a subsequent ovarian malignancy. Black patients (OR = 1.63, 95% CI 1.39-1.92) have the worst survival even after controlling for disease stage and treatment modalities. Determinants of improved overall survival include White race, private insurance, age < 45 years at first primary malignancy diagnosis, prior surgical therapy, and increased latency interval. A prolonged latency interval is associated with a 74% increase in survival (OR = 0.26; 95%CI 0.23-0.30). Conclusions: Determinants of improved survival among patients with subsequent ovarian cancers following a prior primary malignancy include White race, private insurance, and a prolonged latency interval of progression from an initial primary malignancy to a subsequent ovarian cancer.
A mixed-methods study of healthcare provider perspectives on the barriers to enrollment of minority patients on cancer clinical trials.
Authors: Kim Yonghun , O'Shea Mary , Asiedu Gladys , Price Katharine Andress Rowe , Warsame Rahma M. 
Published: June 2022

e18544 Background: Underrepresented minority (URM) patients continue to make up a small percentage of patients treated on cancer clinical trials (CCTs), thus perpetuating health care disparities. Research indicates that engagement of healthcare staff is critical for successful recruitment. Our study sought to better define barriers to minority recruitment to CCT from the research staff perspective. Methods: Semi-structured qualitative interviews were conducted of key stakeholders for CCT enrollment, including clinical research coordinators (CRCs), principal investigators (PIs), and treating clinicians. Questions for the healthcare team explored their experiences caring for URM patients with specific inquiry into the barriers of enrollment/retention and the processes or resources required to better meet patient needs. Results: All hematology and oncology staff at Mayo Clinic Cancer Center were invited to participate via email. Of the 28 who consented, 13 were male (46%), 15 female (54%), and 21% non-white (3 Asian, 2 Hispanic, 1 Black). Of the 19 PIs, 9 were Professors (47%), 5 Associate professors (26%), and 5 Assistant professors (26%). The additional 9 interviewees were CRCs. Select themes with representative quotes and proposed actions can be seen in Table. Conclusions: Recommendations for CCT accrual include accelerating efforts to address workforce diversity gaps, engaging in community outreach, optimization of CCT participation through collaborative care, incentivizing trial participation, and creating flexibility in eligibility criteria.[Table: see text]