bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of clinical trial enrollment on specialty palliative care utilization in pediatric patients with high-grade gliomas.
Authors: Roberts Holly , Franson Andrea Flynn 
Published: June 2022

10057 Background: In pediatric oncology patients, palliative care has been shown to provide numerous benefits, including less intense clinical care in the last month of life, improved symptom management, and dedicated family communication. Pediatric patients with high grade glioma (HGG) represent a patient population particularly well suited for early involvement of palliative care given their high symptom burden and relatively poor prognosis. However, a recent study revealed that pediatric patients with primary malignant central nervous system (CNS) tumors missed multiple opportunities for appropriate palliative care involvement throughout their disease courses. We hypothesize that clinical trial enrollment may lead to a lack of or delay in involvement of palliative care in children and young adults with HGG. Methods: We identified a cohort of 43 deceased pediatric patients with HGG who received care at our institution. IRB exemption was obtained. For each patient, the electronic medical record was reviewed to collect patient demographics, cancer diagnoses and outcomes, clinical trial enrollment, non-clinical trial treatments, and palliative care involvement. Statistical analysis was performed comparing patients enrolled in trials to those not enrolled, employing Fisher’s exact tests for categorical data and t tests for numerical data. Results: Overall, 72% (31/43) of patients had at least one visit with a specialty palliative care provider. 56% (24/43) of patients enrolled in a clinical trial with HGG-directed therapy. 71% (17/24) of patients who enrolled in a clinical trial received specialty palliative care compared to 74% (14/19) of non-trial participants (p = 1.000). Similarly, among patients who received palliative care there was no statistically significant difference in the timing of palliative care involvement, measured from the date of first palliative care contact to date of death, for patients who enrolled in a clinical trial (mean = 177 days) compared to those who did not (mean = 113 days, p = 0.180). Of the 24 patients enrolled in clinical trials, only 7 (29%) had palliative care involvement prior to initiation of study treatment. Conclusions: As our understanding of the genomic landscape of pediatric brain tumors increases, it can be expected that patients electing to enroll in targeted therapy clinical trials will also increase. As such, it is reassuring that our data suggest that trial participation does not interfere with the receipt of specialty palliative care in children with HGG. While not statistically significant, initial palliative care involvement trends toward occurring in closer proximity to death in the patients who are not enrolled on a clinical trial. Overall, it is encouraging that in our pediatric HGG patient cohort, enrollment in clinical trials does not appear to have an adverse impact on specialty palliative care involvement.
Pyrotinib plus nab-paclitaxel in patients with HER2-positive advanced or metastatic breast cancer: A multicenter, single-arm, open-label phase 2 trial.
Authors: Li Huan , Li Zhaohui , Yan Min , Cui Xiujie , Ji Xuening , Fang Fenqi , Zhang Yuyang , Wang Xiaoxin , Wang Yan , Guo Xiangyu , Jing Mingxi , Gao Zhichao , Cao Hui , Dong Fangyuan , Wu Jie , Jiang Cui , Duan Yangyang , Li Xiaorui , Jiang Yujun , Sun Tao 
Published: June 2022

1035 Background: For human epidermal growth factor receptor 2 (HER2) positive advanced or metastatic breast cancer, the standard therapeutic strategy is HER2-targeted agents combined with a taxane. This multicenter, single-arm phase 2 trial was designed to assess the efficacy and safety of pyrotinib (a brand-new generation, irreversible anti-HER2 tyrosine kinase inhibitor) plus nab-paclitaxel in patients with HER2-positive advanced or metastatic breast cancer. Methods: This was a multicenter, single-arm, open-label phase 2 trial conducted at seven centers in China (ChiCTR1900023653). Women aged 18-75 years, with histologically or cytologically confirmed HER-2 positive (immunohistochemistry [IHC] 3+ or positive confirmed by fluorescence in situ hybridization) advanced or metastatic breast cancer and with Eastern Cooperative Oncology Group performance score (ECOG PS) of 0-1 were enrolled. Patients with primary resistance to trastuzumab and bone-only metastases were excluded. Eligible patients received pyrotinib (400 mg, po, qd) plus nab-paclitaxel (125 mg/m2, iv, day 1/8/15) for each 28-day cycle until disease progression, unacceptable toxicity, consent withdrawal or death. The primary endpoint was objective response rate (ORR), defined as the proportion of patients with complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints included progression-free survival (PFS), overall survival, safety and quality of life. Results: Between December 2019 and December 2021, 51 patients were enrolled. The median age was 55 years (range 35–72). Twenty-three patients (45.1%) had ECOG PS of 0. Ten patients (19.6%) with metastatic disease had previously received first-line treatment and 28 (54.9%) had received prior treatment with trastuzumab. More than half (29 of 51, 56.9%) had hormone receptor-positive disease. Visceral metastases occurred in 56.9% of the patients (29 of 51) and 26 patients (51.0%) were menopausal. The data cutoff for the present analysis was January 21, 2022. Among 38 evaluable patients, four patients (10.5%) had CR, 27 (71.1%) had PR, six (15.8%) had stable disease, and one (2.6%) had progressive disease. The confirmed ORR was 81.6% (95% CI 65.1-91.7%). The PFS data were still immature. The most common grade ≥3 treatment-emergent adverse events included neutropenia (14 of 51, 27.5%), diarrhea (10 of 51, 19.6%), fatigue (5 of 51, 9.8%) and peripheral neuropathy (4 of 51, 7.8%). Conclusions: Pyrotinib combined with nab-paclitaxel showed a promising antitumor activity with good tolerance in patients with HER2-positive advanced or metastatic breast cancer. Clinical trial information: ChiCTR1900023653.
Updated overall survival (OS) data from the phase 1b study of tebentafusp (tebe) as monotherapy or combination therapy with durvalumab (durva) and/or tremelimumab (treme) in metastatic cutaneous melanoma (mCM).
Authors: Middleton Mark R. , Hamid Omid , Shoushtari Alexander Noor , Meier Friedegund Elke , Bauer Todd Michael , Salama April K.S. , Kirkwood John M. , Ascierto Paolo Antonio , Lorigan Paul , Mauch Cornelia , Orloff Marlana M. , Evans T.R. Jeffry , Abdullah Shaad Essa , Yuan Yuan , Mitchell James , Hassel Jessica Cecile 
Published: June 2022

104 Background: Tebe is a T-cell receptor bispecific (gp100 x CD3) against gp100 peptide-HLA-A2 complexes that are overexpressed in uveal (UM)/cutaneous melanoma (CM). Tebe is the only therapy to show an OS benefit (HR 0.51) in a phase (Ph) 3 trial in previously untreated metastatic UM. In a prior Ph 1 trial, tebe demonstrated monotherapy activity in anti-PD1 naïve mCM (1-yr OS, approx. 74%). The safety and initial activity of tebe with dose escalation of durva and/or treme in previously treated mCM has been reported. Here, we present updated OS in the subset of mCM patients (pts) relapsed or refractory to prior anti-PD1, a population where recent reports suggest a benchmark 1-yr OS of approximately 55% and median OS of approximately 14 months (mos). Methods: Patients with HLA-A2+, pre-treated mCM received weekly tebe (IV) monotherapy in Arm 4a or in combination with dose escalation of durva and/or treme (IV) on day 15 of each cycle (Arms 1-3). Primary objective was RP2D, secondary objectives were safety and efficacy. Subgroup analyses were performed for durva doses ≥10 mg/kg, a threshold previously defined by Bavarel et al, 2018. Analysis performed on data cut-off 04 January 2022 with median follow up for 14.3 mos. [NCT02535078] Results: 112 pts were treated with median age 59, 23% were ECOG = 1, 37% were BRAFm (73% received prior BRAFi/MEKi), 55% had LDH > ULN. 92% of pts were 2L+ and 74% 3L+; median 3 prior lines. The safety profile of all therapy arms within this study therapy remains very favorable with no new safety signals identified. 97 of 112 pts were documented as relapsed or refractory to prior anti-PD1 (80% also received ipilimumab). Of these 97 pts, 32 received tebe + durva (Arm 1), 13 received tebe + treme (Arm 2), 26 received triplet therapy (Arm 3), and 20 received tebe monotherapy (Arm 4a). 33 of 97 pts in any arm received durva ≥ 10 mg/kg with 1-yr OS of 79%, 2-yr OS of 34%, and median OS of 20 mos. 64 of 97 pts received durva < 10 mg/kg with 1-yr OS of 53%, 2-yr OS of 24%, and median OS of 13 mos. Tebe + durva doublet therapy had similar OS to triplet therapy with tebe + durva + treme: 1-yr OS of 74% vs. 76%, and 2-yr OS of 32% vs. 27%, respectively. Conclusions: Promising OS is seen in mCM similar to mUM, with both tumor types overexpressing gp100. In mCM relapsed or refractory to prior anti-PD1, tebe with anti–PD-L1 continues to demonstrate promising OS (1-yr, approx. 75%) compared to recent benchmarks (1-yr, approx. 55%). These data provide rationale for a randomized study of tebe with anti-PD(L)1 in mCM. Clinical trial information: NCT02535078.
Brain metastasis as first and only metastatic relapse site portends poor outcomes in patients with advanced HER2+ breast cancer.
Authors: Noteware Laura , Broadwater Gloria , Dalal Nicole , Alder Laura , Herndon James Emmett , Floyd Scott R. , Van Swearingen Amanda E.D. , Anders Carey K. , Sammons Sarah 
Published: June 2022

1045 Background: In patients (pts) with stable or no extracranial disease (ECD) presenting with breast cancer brain metastases (BCBrMs), current guidelines recommend pts receive local therapy with radiation +/- surgery, without changing systemic therapy. However, preliminary studies suggest that pts with isolated HER2+ BCBrM without ECD have inferior overall survival (OS) compared to pts with concurrent ECD. Our study further explores the implications of ECD status on intracranial progression free survival (iPFS) and OS. Methods: Retrospective analysis was performed on data from 153 pts diagnosed with initial HER2+ BCBrM who received CNS radiation at Duke between 2008 and 2020. Demographics, dates of metastatic and BCBrM diagnosis, ECD status at first CNS event, systemic therapy, and outcomes were collected. The primary endpoint was iPFS defined as the time from first CNS radiation to the subsequent documentation of intracranial progression (RANO-BM). OS was defined as time from first CNS radiation and first metastatic disease to date of death or last known contact. ECD status was defined by RECIST1.1 from systemic staging scans within 30 days of first CNS event. Results: In this cohort of 153 pts with HER2+ BCBrMs undergoing CNS radiation, > 70% of pts with known ECD status had controlled systemic disease: either no ECD (27%) or stable/responding disease (44%). 64% of pts’ tumors were ER+. Median age was 50 years (range 24 – 75). Most pts (59%) developed first CNS event during adjuvant or 1st/2nd line metastatic therapy. CNS radiation treatment included 48% of pts receiving SRS only, 9% WBRT only, and 43% SRS and WBRT. All pts with no ECD presented with isolated BCBrMs as first metastatic disease. Among pts with known ECD status, OS from initial metastatic disease to death was markedly worse for pts with isolated brain metastases or no ECD (median = 28.4m, 95% CI: 18.1 to not reached) compared to those with progressive or stable/responding ECD (48.8m, 95% CI: 40.5 to 65.0; and 68.1m, 95% CI: 55.2 to 85.7, respectively; log-rank p = 0.004). OS from first CNS involvement to death was significantly worse for pts with progressive ECD (17.8m, 95% CI: 13.7 to 28.8) versus stable/responding (36.6m, 95% CI: 29.7 to 45.2) or no ECD (28.4m, 95% CI: 18.1 to not reached; log-rank p = 0.008). iPFS did not differ statistically among subgroups of pts with known ECD status: progressive ECD (median = 7.7m), no ECD (8.3m), or stable/responding ECD (11.2m) (log-rank p = 0.15). Conclusions: Overall survival in pts with HER2+ isolated BCBrM was markedly inferior to that of pts with progressive or stable/responding ECD. Studies investigating initiation of brain penetrable HER2-targeted therapies earlier in the disease course of isolated HER2+ BCBrMs pts are warranted.
Democratizing germline genetic testing and its impact on prostate cancer clinical decision-making.
Authors: Shore Neal D. , Gazi Mukaram , Pieczonka Christopher Michael , Heron Sean , Cahn David J , Belkoff Laurence , Berger Aaron D. , Mazzarella Brian , Veys Joseph , Morris David , Engelman Alexander , Dato Paul , Bevan-Thomas Richard , Cornell Robert , Layman Paige , Hatchell Kathryn E. , Heald Brandie , Nielsen Sarah M. , Nussbaum Robert Luke , Esplin Edward D. 
Published: June 2022

10500 Background: Approximately 10-15% of prostate cancer (PCa) patients (pts) have a pathogenic germline variant (PGV). Identification of a PGV has important implications affecting decisions regarding cancer screening, treatment selection, and family cascade testing. There exists limited data documenting real world recommendations post germline genetic testing (GGT). This study was designed to collect clinician reported outcomes from PCa pts who underwent GGT. Methods: An IRB-approved, nationwide, prospective registry recruited unselected PCa pts from 15 community and academic urology practices. Pts underwent an 84-gene panel test, with clinical outcomes collected via clinician-completed case report forms > 1-month post GGT. Statistical significance was determined by two-tailed Fisher’s exact test. Results: 982 predominantly white (75.9%), non-metastatic (80.7%) males with PCa were recruited; 56.9% met National Comprehensive Cancer Network (NCCN) GGT criteria. Average age was 65.3 years at PCa diagnosis. PGVs, most commonly CHEK2 (17) and BRCA2 (10), were identified in 100 (10.2%) pts; 34 (34%) of these did not meet NCCN GGT criteria. Among PGV positive pts, 241 recommendations were made (Table). They were more likely to have changes to treatment (p < 0.0001), follow up (p < 0.0001) and cascade testing recommendations (p < 0.0001) than those with negative/variant of uncertain significance (VUS) results. There were no significant differences in changes to treatment (p = 0.4471) or follow up (p = 0.861) for pts who met NCCN criteria versus those who did not. 7 pts with PGVs received targeted therapy or were referred to a clinical trial. 5 pts with VUS results were also referred to a clinical trial. Among these 12 pts, 6 (50%, 2 CHEK2 PGV, 1 ATM PGV, 1 VUS each ATM, BLM, CHEK2) did not meet NCCN GGT criteria. Referral to a genetic counselor was the most common follow up recommendation for those with PGV (38 patients, 38%) and VUS results (66, 13.7%). The most commonly reported impact to health outcomes for those with negative results was knowledge/reassurance (38, 7.88%). Conclusions: This study showed that GGT did influence PCa pts care. Appropriately, pts with PGVs received a greater number of recommendations for relatives, changes to follow up and treatment. [Table: see text]
Racial and regional disparities in metastatic breast cancer.
Authors: Singhal Sachi , Desai Devashish , Khosla Akshita , Lanade Oladimeji , Potdar Rashmika 
Published: June 2022

10516 Background: Breast cancer is the most commonly diagnosed malignancy in American women, with about 281,500 new reported cases this year, 3.8 million women living with an active or history of breast cancer, and a lifetime occurrence of 1 in 8 women in this nation. Racial disparities persist despite the advent and implementation of screening by national agencies. AA females are less likely to be diagnosed with breast cancer, and yet bear an arbitrarily high burden of mortality of this malignancy. Socioeconomic variables and lifestyle are the most plausible explanations of this discrepancy. Even in clinical trials, there remains an underrepresentation of all ethnic minorities. Encouragement of guideline based screening for all along with constant follow ups, access to health insurance and a more uniform representation in trials are the cornerstone of eliminating these disparities. Methods: Data for this study was obtained from the 2016-18 Nationwide Inpatient Sample (NIS) which comprises 20% of the total US hospital discharges. We identified all patients with a primary diagnosis of Malignant Neoplasms of Breast. In-hospital mortality, race and hospital regions for the given patients were studied. Baseline characteristics of participants were summarized using descriptive statistics. The patient population was stratified as per race, hospital region, gender, therapy they received and family history. Logistic regression was performed to derive the odds ratio while adjusting for different variables. Further details: https://www.hcup-us.ahrq.gov/ . Results: 99, 543 patients with metastatic breast cancer were identified, and almost 99% of them were females. 67% of the population was comprised of Caucasians, 16.91% African Americans (AA), 9.14% Hispanics and 3.28% Asians and Pacific Islanders (API). AAs had the most reported deaths at 5.54%, followed by APIs at 4.80% and Caucasians 4.09% (p < 0.0001). The odds of dying were significantly higher in AA population when compared to Caucasian population (OR 1.391 (1.286-1.504)), and the odds were consistently higher across all regions of the US. In terms of regional variation, it was seen that races identifying as “others' ' had significantly higher odds of dying in the North East (OR 1.646 (1.238-2.189)) and the West (OR 1.503 (1.059-2.133)). Conclusions: It is crucial to identify racial disparities in diagnosis, treatment and mortality before we devise a blueprint to tackle this incongruity. This highlights the significance of universal screening and better health insurance coverage in addition to recognition of reasons behind these differences.
Increase in incidence of advanced-stage breast cancer in Asian women versus White women: Can this be explained by the lower utilization of mammograms?
Authors: Liao Cheng-I , Caesar Michelle Ann P. , Lee Danny , Chan Chloe , Kapp Daniel Stuart , Chan John K 
Published: June 2022

10524 Background: To examine trends in postmenopausal breast cancer and mammogram utilization in Asian and White women in the United States. Methods: Data on postmenopausal breast cancer was obtained from the United States Cancer Statistics Public Use Database from 2001 and 2018. Rates of mammogram screening for women ages 18 and older were evaluated using the Behavioral Risk Factor Surveillance System (BRFSS) between 2000 and 2018. Obesity rates for women ages 18 and older were extracted from BRFSS between 2001 and 2016. SEER*Stat 8.3.8 and Joinpoint regression program 4.8.0.1 were used to calculate incidence trends. Breast cancer incidence and trends were described using average annual percent change (AAPC). Mammogram screening trends were described using average biennial percent change (ABPC). Obesity trends were described using AAPC. Age groups were divided into five-year or ten-year intervals. Results: The incidence of metastatic postmenopausal breast cancer in women was 19.48/100,000 in 2018 has increased by 1.03% annually over the past eighteen years (p = 0.000). In 2018, the incidence of advanced-stage breast cancer in Asian and White women was 12.17/100,000 and 19.17/100,000 respectively. Over time, the incidence of advanced-stage breast cancer has increased in Asian women by 2.19% annually (p = 0.000), but remained stable in White women. In a subset analysis of early-stage breast cancer, there was no difference in both Asian and White women. Using the BRFSS data, we evaluated the utilization of mammograms. In the overall population, 20.92% were newer screened and this was higher in Asian women at 40.99% compared to 18.17% in White women in the year 2018. Given the potential association of obesity and breast cancer, we then evaluated the rate of obesity in these two groups. Our data showed that the incidence of obesity was low in Asian women at 12.8% compared to 28.13% in White women. Conclusions: There is an increased incidence of advanced-stage breast cancer in Asian women in the U.S. Although Asian women are less obese but they are also less likely to undergo screening compared to White women.
Designing a decision aid for cancer prevention.
Authors: Milton Shakira R , Macrae Finlay , McIntosh Jennifer , Saya Sibel , Emery Jon D. 
Published: June 2022

10531 Background: Australian guidelines recommend those aged 50 to 70-years-old without contraindications, consider taking low-dose aspirin (100 mg – 300 mg per day) for at least 2.5 years to reduce their risk of colorectal cancer. To increase uptake of the new guidelines, we hypothesized that a decision aid (DA) would help facilitate a discussion between clinicians and patients about aspirin chemoprevention. We aimed to design a DA with clinician and consumer input including state-of-the-art expected frequency trees (EFTs). We aimed to explore clinicians’ opinions about using EFTs with their patients during consultations and gain consumers feedback on DAs including their understanding and their hypothetical decision to take aspirin or not. Methods: Semi-structured interviews were conducted with relevant clinicians including familial cancer clinic staff (geneticists, oncologists and genetic counsellors), gastroenterologists, pharmacists, and general practitioners (GPs). Focus groups were conducted with consumers in the target age range of the guidelines. DAs were developed through an iterative process. The clinician and focus group interview schedules covered ease of comprehension, design, potential effects on decision making, and approaches to implementation of the DA. Coding was inductive and the focus group interviews were independently coded by two researchers. Themes were developed through consensus between the authors. Final versions of the DAs were proposed to consumers for their final approval after all changes were made. Results: Sixty-four interviews were completed with clinicians between March and October 2019. Twelve consumers, aged 50 to 70 years, participated in two focus groups in February and March 2020. The clinicians agreed that the EFTs would be helpful to facilitate a discussion with patients but suggested including an additional estimate of the effects of aspirin on all-cause mortality. Clinicians agreed that patients would benefit from being shown the EFT in a consultation. The consumers felt favorable about the DA, especially if used with a clinician, and suggested some additional changes to the design and wording to improve ease of comprehension. Conclusions: We have designed a DA using novel approaches to communicate risks and benefits of low dose aspirin for cancer and cardiovascular disease prevention. The DAs are currently being trialled in the SITA trial in general practice to determine its impact on informed decision-making and aspirin uptake.