bluuebunny/crossref_metadata_2025_split huggingface dataset:
Invasive Paget’s disease of the breast versus genitalia versus skin: What are the demographic and prognostic differences?
Authors: Moon Ashley S. , Liao Cheng-I , Chen Hsiu-Min , Lee Danny , Chan John 
Published: June 2021

e17577 Background: Invasive extramammary Paget’s disease is most commonly in the vulva but can also occur in other genitalia as well as primary skin locations (face, scalp, neck, trunk, extremities). We aim to determine the clinicopathologic and prognostic factors of invasive Paget’s disease of the breast, genitalia and skin. Methods: Data on patients with invasive Paget’s disease of the breast, genitalia and skin were collected between 2001 and 2015 from the National Cancer Data Base Participant Use File 2016. Univariate, multivariate analyses, and Kaplan-Meier survival analysis were performed by SAS. Results: 10, 122 female patients were eligible, of which 7, 051 had invasive disease (breast n = 5, 105, genitalia n = 1, 717, skin n = 229) and the remainder had in situ disease. Median age for invasive disease was 63 years for breast, 73 years for genitalia and 75 years for skin. Among Whites, the proportion of invasive Paget’s of breast, genitalia, and skin was 70.8%, 25.8%, 3.4%; Blacks 93.8% breast, 5.3% genitalia and 0.9% skin; Asian/Pacific Islanders 65.0% breast, 31.8% genitalia and 3.2% skin. Among treatment institutions, academic centers treated 30.2% of invasive breast, 48.9% genitalia and 51.5% skin. Surgery was performed in 89.4% of invasive breast compared to 21.1% genitalia and 46.7% skin. Radiotherapy was administered to 25.3% of invasive breast, 3.0% genitalia and 15.3% skin. Chemotherapy was given to 28.0% of breast, 1.9% genitalia and 5.7% skin. Early stage (I or II) disease was diagnosed in 70.8% of invasive breast, 63% genitalia and 30.6% skin. Five-year OS from any cause for patients with invasive Paget’s disease of breast, genitalia and skin was 81.9%, 83.8%, and 69.9%, respectively. In univariate analysis, older age (HR 3.75, 95% CI 3.27-4.31, p < 0.001), Black race (HR 1.21, 95% CI 1.00-1.46, p = 0.046), history of other cancer (HR 1.53, 95%CI 1.36-1.71, p < 0.001), higher comorbidity score (HR 2.12, 95%CI 1.88-2.39, p < 0.001), higher stage (HR 4.25, 95%CI 3.73-4.85, p < 0.001), and no surgical treatment (HR 3.47, 95% CI 2.87-4.19, p < 0.001) were associated with worse survival. In multivariate analysis, invasive Paget’s of the skin was associated with the worst survival (HR 1.56, 95% CI 1.19-2.05, p = 0.001). For all three types of invasive Paget’s disease, better prognosis was associated with Asian/Pacific Islander race (HR 0.49, 95% CI 0.31-0.80, p = 0.004), income ≥ $63, 000 (HR 0.83, 0.70-0.98, p = 0.028) and treatment at an academic/research center (HR 0.78, 0.62-0.99, p = 0.037). Conclusions: Invasive Paget’s disease of the breast is 3-fold more common than genitalia with younger age at diagnosis. Most are diagnosed at early stages with good prognosis. Blacks have a higher proportion of invasive Paget’s disease of the breast than other races. Invasive Paget’s disease of primary skin had the poorest prognosis.
Cytokines performance during nivolumab treatment: A subgroup analysis of NIVACTOR study.
Authors: Denaro Nerina , Paccagnella Matteo , Galizia Danilo , Falletta Antonella , Abbona Andrea , Gammaitoni Loretta , Fiorino Erika , De Zarlo Lorena , Bossi Paolo , Sangiolo Dario , Licitra Lisa F. , Aglietta Massimo , Merlano Marco Carlo 
Published: June 2021

e18008 Background: Nivolumab is approved for 2nd line R/M SCCHN, but only ̃20% of patients will benefit. Therefore, there is an unmet need for predictive markers. Nivactor is a prospective real-life study of nivolumab in SCC-HN. We report an ancillary study on circulating cytokines in a subgroup of patients from Nivactor. Methods: We analysed changes of circulating cytokines (IL-2/4/5/6/8/10/12/13/15, CCL-2/4/22, CXCL-10, IFN-γ, TGF-β, TNF-α, VEGF) during nivolumab therapy at baseline (T0), cycle 3 (T1), cycle 7 (T2) and at disease progression (TPD). ROC analysis identifies cytokines that correlate best with PFS and OS and calculate cut-off points. Cox analysis was performed to assess HR. Hierarchical Clustering on Principal Components (HCPC) was performed to cluster pts and then compared clusters for good or poor PFS and OS. Correction for multiplicity was applied. Results: 19 pts were analysed. Using ROC analysis, we were able to identify cut-off values correlated with PFS at T0 only for IL-6 and IL-10. Similarly, we identified IL-6, IL-10, TGF-β and VEGF cut-off for OS. Then we performed Cox analysis dividing the population based on the identified cut-offs and we found that pts with IL-6 or IL-10 lower than cut off had a significant better PFS and OS (p = 0.049 and p = 0.003 for PFS, respectively; p = 0.029 and p = 0.006 for OS, respectively). TGF-β lower than cut-off correlates with better OS (p = 0.02). Interestingly, pts with all the 3 cytokines below the cut-off show the best OS. Finally, we performed a multivariate analysis using HCPC to identify 4 clusters of pts. Cluster 2 has the best PFS and OS than all other cluster considered together (p = 0.001 and p = 0.004 respectively). Patients in cluster 2 show at T0 lower IL-6/10/15 and at T1 lower IL-5/10 and higher IFN-γ compared to the others. Longitudinal analysis among the 3 time points shows that the increase of IFN-γ, IL-5 and IL-10 between T0 and T1 correlates with better PFS (p = 0.01, p = 0.03, p = 0.02, respectively); only IFN-γ and IL-5 correlates with better OS (p = 0.04; p = 0.02, respectively). Conclusions: ROC analysis can identify cytokines whose basal level may predict patients that could benefit from nivolumab treatment: low IL-6 and IL-10 positively influence both PFS and OS. Low TGF-β does not correlate with PFS but only with better OS and can be considered a pure prognostic marker. Longitudinal analysis offers information on the effect of treatment on circulating cytokines, and show that the subgroup of pts with better PFS exhibits an increase of inflammatory cytokines values.
NTRK, ALK and RET rearrangements in salivary gland cancer.
Authors: Kutukova Svetlana , Imyanitov Evgeny , Beliak Natalia P. , Ivaskova Julia V. , Razumova Alexandra 
Published: June 2021

e18023 Background: We investigated the prevalence of rare genes rearrangements in salivary gland adenocarcinomas and the impact of these fusions on overall survival (OS) and progression free survival (PFS). Methods: For 51/60 (85.0%) patients with different types salivary gland adenocarcinomas (stage I-IVA), sufficient tumor tissue was available for molecular characterization by polymerase chain reaction (PCR) and has been tested for NTRK, ALK, ROS1, RET and MET deletion. OS and PFS curves were estimated with the Kaplan-Meier method and compared using the log-rank test. Results: Two cases (3.92%) of NTRK translocation were found, both are a classic rearrangement of ETV6ex5; NTRK3ex15. Of the other alterations, 2 cases (3.92%) of unbalanced ALK expression. However, it was not possible to establish the option of rebuilding. In addition, were found 2 cases (3.92%) of highly balanced expression of NTRK2 and ALK, and one case (1.96%) of high expression of ROS1. RET mRNA expression was detected in 13 of 48 cases (27.08%). NTRK, RET, ALK and ROS1 fusions were equally common in both men and women (p = 0.89), not depending on age (0.76). All patients bearing ALK, RET and NTRK fusions had shorter overall survival - 13.2 months, 95% confidence interval [CI] 13.0 to 32.0 months in multivariable model 105.0 moth (95% CI 105.0-105.0) in patient's group without mutations (p = 0.1817); and shorter PFS: 5.0 month (95% CI 5.0-16.0) vs not reached PFC in group (mean of PFS 63.15±5.58; 95% CI 52.20-74.09) without mutations (p = 0.0467). ALK fusion is an independent poor prognosis factor affecting on OS: p = 0.0168, hazard ratio (HR) = 8.65 (95% CI 1.47-50.77); and poor prognosis factor affecting on PFS: p = 0.0170, HR = 7.13 (95% CI 1.42-35.80). Conclusions: ALK, NTRK, ROS1 and RET mutations define a new rare subtype of salivary gland adenocarcinomas with enormously poor prognosis. The presence ALK-mutation is an independent poor prognosis factorб negatively affecting both overall survival and progression-free survival. It’s advisable to consider the possibilities of using ALK, NTRK and RET inhibitors in this cohort of patients.
Comparison of diagnostic characteristics between sentinel lymph node biopsy (SLNB) and radio-guide elective neck dissection (RGEND) in patients with T1-2N0 oral tongue cancer.
Authors: Kotov Maxim , Radzhabova Zamira , Novikov Sergey 
Published: June 2021

e18037 Background: Elective neck dissection remains the standard treatment for cN0 oral cancer due to the high incidence of occult lymph node (LN) metastases. Sentinel lymph node biopsy (SNB) might be a less morbid alternative to neck dissection. Diagnostic value of SLNB depends on the number of sampled LNs. We aimed to compare the diagnostic features of SNB and RGEND in patients with T1-2N0 oral tongue cancer. Methods: A prospective study was conducted in patients with cT1-2N0M0 oral tongue squamous cell carcinoma treated between January 2016 and December 2020. The procedure included SLNB ollowed by immediate extent ipsilateral neck dissection. SLNB included accumulated radiotracer LNs, which located close to the primary tumor. RGEND included LNs accumulated radiotracer with all LNs located at the same level. Pathology assessment was performed and diagnostic characteristics were compared between SLNB and RGEND. Results: A total of 38 patients were enrolled. The mean age was 55.7±13,1. Twenty-four patients had unilateral lymph flow and 14 had bilateral. Sentinel LNs were located at levels IIa-III. Occult metastases were found in 15,8% (n = 6) of patients. The median number of LNs in the sample was 3 (IQR: 1-5). The sensitivities of SLNB and RGEND were 50% (95%CI: 15.7 - 84.3) and 100% (95%CI: 54.7-100), respectively, p-value = 0.001. Specificity was similar among groups: 100% (95%CI: 88-100) and 100% (95%CI: 89.1-100. SLNB had accuracy of 89.5% (95%CI: 77.2 - 97), and RGEND 100% (95% CI: 90.7-100), p-value = 0.001. Positive predictive value (PPV) was similar among groups. Negative predictive value (NPV) was 88.2% (95% CI: 78.9 - 93.7) in SLNB and 100% (95%CI: 91-100) in RGEND groups. p-value = 0.001. Conclusions: SLNB and RGEND have high rates of specificity, accuracy, PPV, and NPV, regardless of sampling size. RGEND has the highest sensitivity in patients with cT1-2N0 oral tongue cancer.
Trainings needs of allied health professionals caring for sexual and gender minority adolescents and young adults with cancer: A qualitative analysis.
Authors: Alpert Ash B. , Gampa Vikas , Vadaparampil Susan Thomas , Quinn Gwendolyn P. 
Published: June 2021

e18532 Background: Little is known about the training needs of allied health professionals who provide reproductive health counseling and other support services to sexual and gender minority (SGM) adolescent and young adult (AYA) people with cancer. Methods: A 28-item electronic survey with 4 qualitative items was distributed to 601 allied health professionals who had participated in a training focused on reproductive health needs in AYA people with cancer. Open-ended questions invited respondents to describe personal experiences, reservations, and suggestions for improving SGM AYA cancer care. Using an interpretive description methodology, two investigators independently analyzed qualitative survey responses noting thematic saturation. Together, they refined themes, resolving disagreements with consensus. Interrater reliability was 88%. Results: 321 people participated in the survey and 190 answered open-ended questions. Themes included: 1) an ecosystem exists around patients’ interactions with clinicians and institutions; 2) institutional and individual assumptions result in stigmatization of SGM AYA people with cancer; 3) accommodating patients and providing clinicians with relevant education and experiences are initial steps to decrease stigma; and 4) improving the care for SGM AYA people with cancer may require transformative approaches that incorporate intersectional frameworks and challenge current systems. Conclusions: Improving the quality of care for SGM AYA people with cancer will require systemic and institutional change as well as educational interventions.
Patterns of presentation among New Zealand Māori with pancreatic cancer at Lakes District Health Board.
Authors: Camburn Laura , Hari Dass Prashanth 
Published: June 2021

e18553 Background: New Zealand (NZ) Māori have higher rates of pancreatic cancer than other ethnic groups in NZ. Lakes District Health board (LDHB) has one of the highest proportion of Māori patients within New Zealand, 34.7% compared to 15.7% nationally. We aimed to review the patterns of presentation of patients diagnosed with pancreatic cancer at LDHB between ethnicities. Methods: Patients diagnosed with pancreatic cancer at LDHB between 01 Jul 2014 to 31 Mar 2020 were identified using the faster cancer treatment data and regional hospice referral data. This was cross checked against surgical and oncology referrals. Electronic notes were reviewed to collect data on ethnicity, patient demographics, & presentation. Results: 69 patients were identified; 25 Māori patients and 44 New Zealand European (NZE) patients. The mean age at diagnosis was 63.4 years for Māori and 73.4 years for NZE patients. 22 (88%) Māori patients were below the age of 75 at diagnosis compared to 24 (55%) NZE patients. In both groups there were more affected males than females. Risk factors such as positive smoking history, obesity and diabetes were more prevalent in Māori patients (80% v 43%, 40% v 16%, 44% v 20% respectively). Māori were more likely to present with metastatic disease compared to non-Māori at presentation (64% v 52%). Conclusions: Māori pancreatic cancer patients in our region were more likely to present younger with metabolic syndrome and more advanced disease compared to NZE patients.
Excess body weight association with various cancer: A United States population-based study 2021.
Authors: Alkrekshi Akram , Arroyo Suarez Raul , Kassem Ahmad Nader 
Published: June 2021

e18558 Background: Excess body weight (EW) is a rising healthcare issue affecting over two-thirds of the United States (US) population, and it is a risk factor for various cancer. Methods: We used Explorys, IBM, a US database that includes ̃ 73 million patients. We evaluated non-gastrointestinal cancers prevalence based on age (18-64 and ≥ 65 years; for female cancers 18-49 and ≥ 50 years), race; Caucasians (C) and African-Americans (AA), and weight; normal weight (N) with BMI 18.5- 24.9 kg/m2 and EW for BMI ≥ 25 kg/m2. Compared to NW, the odds ratio (OR) and 95% confidence interval (CI) for multiple cancer rates in the EW group were calculated. p-value of <0.001 was considered significant (S) and > 0.001 as non-significant (NS). Results: A population of 26.9 million was included. C 85.6%, AA 14.4%. See table. Conclusions: A strong association between EW and urological cancers (prostate, bladder, renal), non-Hodgkin's lymphoma, multiple myelomas (MM), breast cancer, endometrial cancer, ovarian cancer in C 18-64 yrs but not in C ≥ 65 yrs with the exception for kidney cancer. A similar finding in AA 18-64 yrs for cancers of prostate, renal, breast, uterus, and MM compared to AA ≥ 65 yrs. EW is possibly more oncogenic earlier in life, especially in C.[Table: see text]
Breast cancer survivorship and level of institutional involvement utilizing integrative oncology.
Authors: Crudup Terri , Li Linna , Dorr Jennifer Wright , Lawson Elizabeth , Stout Rachel , Niknam Pedram Vazifeh , Jones Judi , Steen Robert , Lu Lynn L , Casner Susan , Wang Yi , Scott James , Zanine Shelby , Robertshaw Stacey , Broderick Gabriella , Singh Simarpreet , Lu Jingsong , Zhou Li , Palommella Vaishali , Jonas Wayne 
Published: June 2021

e18588 Background: A growing body of evidence has shown that a Whole Person Integrative Oncology approach, adding the use of complementary and lifestyle therapies to cancer treatments, benefits patients by improving patient-reported outcomes and potentially extending overall survival. This study aims to investigate the relationship between the survival outcomes of breast cancer patients and the level of involvement in Integrative Oncology at the institutions treating those patients. Methods: Between January 2013 and December 2014, 4,815 breast cancer patients were available for survival analysis using an established claims-based method. These patients were filtered to include those with clear mapping to treating oncologists and treating institutions. To measure each institution’s level of Integrative involvement, a scoring system was developed with the Samueli Foundation and oncologists from each institution were surveyed on the education, availability, and financing of 12 complementary and lifestyle approaches during the treatment timeframe. Statistical analysis using multivariate modeling with logistic regression and a lasso approach were employed. 19 variables across region, patient demographics, and institutional profile were included. Model coefficients are exponentiated and presented as odds-ratios, with less than one having a negative impact on survival and greater than one improved survival. Results: We identified 173 patients mapping to 103 institutions and 103 oncologists who responded to our survey. Median age of breast cancer patients was 51 (range: 32-76). 14 of the patients (8%) were identified as metastatic. The 5-year overall survival among the Low scoring institutions was 89%, Low-Mid 96%, Mid-High 96%, High 95%. Chi square testing across these cohorts showed no statistically significant difference between them. On multivariate modeling, age, geography, metastatic status, academic setting, and Integrative score were predictors of 5-year survival. The most significant 9 variables are shown in Table. Having metastatic disease, treatment at a non NCCN designated facility, treatment at Midwest or Western Region predicts for lower 5-year survival. Older age, treatment at an academic setting, and having a High or Low-Mid Integrative score are predictors of improved survival. Conclusions: This study suggests that in addition to traditional predictors of survival such as metastatic disease and younger age, patients receiving treatment at an institution that supports Integrative Oncology programs may be associated with improved survival. More work is needed to evaluate the relationship between Integrative Oncology and cancer treatment outcomes.[Table: see text]
Clinical outcomes of cancer patients with COVID-19: A systematic review and meta-analysis.
Authors: Alasfour Maryam , Alawadi Salman , AlMojel Malak , Costa Philippos Apolinario , Barreto Coelho Priscila , Plate Thomas , Ahn Soyeon , Lopes Gilberto 
Published: June 2021

e18600 Background: Patients with coronavirus disease 2019 (COVID-19) and cancer have worse clinical outcomes compared to those without cancer. Primary studies have examined this population, but most had small sample sizes and conflicting results. Prior meta-analyses exclude most US and European data or only examine mortality. The present meta-analysis evaluates the prevalence of several clinical outcomes in cancer patients with COVID-19, including new emerging data from Europe and the US. Methods: A systematic search of PubMED, medRxiv, JMIR and Embase by two independent investigators included peer-reviewed papers and preprints up to July 8, 2020. The primary outcome was mortality. Other outcomes were ICU and non-ICU admission, mild, moderate and severe complications, ARDS, invasive ventilation, stable, and clinically improved rates. Study quality was assessed through the Newcastle–Ottawa scale. Random effects model was used to derive prevalence rates, their 95% confidence intervals (CI) and 95% prediction intervals (PI). Results: Thirty-four studies (N = 4,371) were included in the analysis. The mortality prevalence rate was 25.2% (95% CI: 21.1–29.7; 95% PI: 9.8-51.1; I 2 = 85.4), with 11.9% ICU admissions (95% CI: 9.2-15.4; 95% PI: 4.3-28.9; I 2= 77.8) and 25.2% clinically stable (95% CI: 21.1-29.7; 95% PI: 9.8-51.1; I 2 = 85.4). Furthermore, 42.5% developed severe complications (95% CI: 30.4-55.7; 95% PI: 8.2-85.9; I 2 = 94.3), with 22.7% developing ARDS (95% CI: 15.4-32.2; 95% PI: 5.8-58.6; I 2 = 82.4), and 11.3% needing invasive ventilation (95% CI: 6.7-18.4; 95% PI: 2.3-41.1; I 2 = 79.8). Post-follow up, 49% clinically improved (95% CI: 35.6-62.6; 95% PI: 9.8-89.4; I 2 = 92.5). All outcomes had large I 2 , suggesting high levels of heterogeneity among studies, and wide PIs indicating high variability within outcomes. Despite this variability, the mortality rate in cancer patients with COVID-19, even at the lower end of the PI (9.8%), is higher than the 2% mortality rate of the non-cancer with COVID-19 population, but not as high as what other meta-analyses conclude, which is around 25%. Conclusions: Patients with cancer who develop COVID-19 have a higher probability of mortality compared to the general population with COVID-19, but possibly not as high as previous studies have shown. A large proportion of them developed severe complications, but a larger proportion recovered. Prevalence of mortality and other outcomes published in prior meta-analyses did not report prediction intervals, which compromises the clinical utilization of such results.
Optimism bias in the design of phase III randomized control trials (RCTs) evaluating PD-1/PD-L1 targeting monoclonal antibodies (mAbs).
Authors: Al-Showbaki Laith , Almugbel Fahad , Alqaisi Husam , Amir Eitan , Chen Eric Xueyu 
Published: June 2021

e18616 Background: PD-1/PD-L1 targeting monoclonal antibodies (mAbs) improve outcomes in multiple cancer types. Multiple mAbs are in clinical development, and many randomized control trials (RCTs) have been completed or are in progress. These RCTs compete for limited clinical trials infrastructure, human resources and patients. Since the hypothesized benefit of an intervention is a critical determinant of the number of patients required for an RCT, it is crucial that the expected benefit be estimated appropriately. We examined the hypothesized hazard ratio (HHR) and the observed hazard ratio (OHR) in RCTs evaluating PD-1/PD-L1 targeting mAbs. Methods: Publications of RCTs evaluating at least one PD-1/PD-L1 targeting mAbs approved by the US Food and Drug Administration were identified through PubMed searches. The primary publication for each RCT and its associated protocol were retrieved. Two investigators independently extracted HHR, OHR for the primary endpoint among other data elements. The differences (∆HR) in HHR and OHR were analyzed statistically. Updated OHRs (uOHR) were extracted from reports with extended follow-ups. Results: 49 RCTs enrolling 36867 patients were included. 45/49 RCTs were in the palliative setting. HHR was met or exceeded in 22 (45%) RCTs. The mean HHR and OHR were 0.672 and 0.738, respectively. The mean ∆HR was 0.067 (range: -0.300 to 0.895, 95% confidence interval = 0.003 – 0.130). A lower magnitude of effect than hypothesized in 12/29 RCTs in non-small cell lung cancer, melanoma and renal cell carcinoma, but in 15/20 RCTs in other cancer types. OHR was ≥ 1.0 in 6 RCTs (12%). In the palliative setting, ∆HR was larger in more heavily pre-treated patients. PD-L1 expression was not associated with magnitude of effect. However, a higher magnitude of effect was observed for RCTs published in the New England Journal of Medicine. For 18 RCTs with extended follow-ups, uOHR was higher than OHR in 8. Conclusions: The majority of published RCTs evaluating PD-1/PD-L1 targeting mAbs did not achieve their hypothesized magnitude of effect. Investigators’ optimism regarding these agents should be combined with more realistic expectations. The optimism bias requires attention from the cancer clinical research community given the number of these agents in development and the intense interest in evaluating these agents in various disease settings.