bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychosocial impacts of the COVID-19 pandemic on young adult cancer survivors and parents of children with cancer.
Authors: Smith Stephanie M , Kumar Dhanya , Benedict Catherine , Heathcote Lauren C. , Aftandilian Catherine , Bondy Melissa , Schapira Lidia
Published: June 2021

10050

Background: The COVID-19 pandemic has affected oncology practice in a variety of ways. We sought to evaluate the impact on pediatric oncology parent and young adult (YA) patient experiences, concerns, and perceived stress. Methods: We conducted a cross-sectional Internet-based survey of parents and YA patients in the pediatric oncology and survivorship clinics at Stanford between June-December 2020. Patients were recruited in person by clinic staff or through the electronic patient health portal. Surveys (available in English and Spanish) included the NIH Perceived Stress Scale (PSS-10) and investigator-developed questions evaluating clinical practice changes, concerns about health and cancer care, and pandemic-related challenges. Bivariate analyses evaluated associations between demographic, clinical, and pandemic-related factors and (a) concern about the pandemic affecting health and cancer care, and (b) perceived stress. Results: Among 81 participants (66 parents, mean age 41.6 ± SD 9.6; 15 YAs, mean age 21.9 ± 8.4 years), 37% self-identified as Hispanic/Latino, 36% non-Hispanic white, and 21% Asian. Twenty-eight percent were on treatment and 47% had completed treatment (79% < 5 years prior). Thirty percent reported cancer-related appointment changes, largely rescheduling (75%) and/or switching to telehealth (42%). Nearly half (45%) of parents and 27% of YAs reported feeling ‘very’ or ‘extremely’ concerned about the pandemic affecting their child’s/their health or cancer care. Race/ethnicity emerged as the only demographic feature that was significantly associated with high concern (p = 0.018), with 57% of Hispanic/Latino and only 21% of non-Hispanic white respondents reporting high levels of concern. Specific concerns included fear of severe infection, immunosuppression, and whether infection would change treatment and compromise effectiveness. Parents and YAs reported ‘a lot’ or ‘a great deal’ of challenges in their personal/family life (61%) and work/professional life (48%). Among these were having less support from friends/family (35%), reduced wages/work hours (31%), and job loss (20%) with 20% reporting ≥ 3 challenges. On the PSS-10, stress in the past month was high for parents (mean 30 ± 4) and YAs (mean 31 ± 5.1) on a scale of 0-40. Risk factors for higher stress included: male gender (p = 0.028), less support from family/friends (p = 0.002), and experiencing ≥ 3 pandemic-related challenges (p = 0.013). Conclusions: Our findings confirm the prevalent worry and stress that pediatric oncology patients and families are experiencing during the COVID-19 pandemic. Better communication about cancer care service changes may help to alleviate some concerns. Supportive care resources may also help patients and families cope with psychosocial stressors, particularly among at-risk groups.
Community-based lung cancer screening adherence to Lung-RADS recommendations.
Authors: Kim Roger , Rendle Katharine A. , Neslund-Dudas Christine , Greenlee Robert T. , Burnett-Hartman Andrea N. , Honda Stacey A. , Simoff Michael J. , Croswell Jennifer M. , Ritzwoller Debra P. , Vachani Anil
Published: June 2021

10540

Background: In the NLST and NELSON trials, most low-dose CT (LDCT) screen-detected lung cancers were not diagnosed during the first round of screening, suggesting that longitudinal adherence to lung cancer screening (LCS) recommendations is key. Adherence was as high as 95% in clinical trials, but limited data exist regarding LCS adherence in clinical practice. We aimed to determine adherence to Lung-RADS recommendations among community-based patients undergoing LCS. Methods: We performed a multicenter retrospective cohort study of patients screened for lung cancer at healthcare systems within the Lung Population-based Research to Optimize the Screening Process (PROSPR) Consortium. We included 55-80 year-old current or former smokers who received a baseline (T0) LDCT with a Lung-RADS score between January 1, 2015 and September 30, 2017 and excluded patients who were diagnosed with lung cancer prior to the T0 scan. Over a 24-month period, we calculated the proportion of patients adherent to Lung-RADS recommendations and evaluated associations with patient-level (age, sex, race, ethnicity, smoking status, body mass index, Elixhauser comorbidities, year of T0 scan, and Lung-RADS score) and census tract (median family income, level of education) data, using multivariable logistic regression with mixed effects to account for site variability. Results: Of the 6,723 patients in our cohort (median age 65 years [IQR 60-69]; 45.1% female; 73.0% white; 59.0% current smokers), 5,583 (83.0%) had Lung-RADS 1 or 2 T0 scans, 733 (10.9%) Lung-RADS 3, 274 (4.1%) Lung-RADS 4A, and 133 (2.0%) Lung-RADS 4B or 4X. Overall, 55.2% (3,709/6,723) of patients were adherent (Table). In the final multivariable model, Black patients had reduced adherence compared to white patients (adjusted odds ratio [aOR] 0.79, 95% CI 0.66-0.94), while greater adherence was observed in former smokers compared to current smokers (aOR 1.33, 95% 1.19-1.49). Compared to individuals with a negative T0 scan (Lung-RADS 1 or 2), those with Lung-RADS 3 (aOR 1.56, 95% CI 1.31-1.86), 4A (aOR 1.63, 95% CI 1.24-2.15), or 4B/4X (aOR 3.59, 95% CI 2.30-5.60) T0 scans had greater odds of adherence. Conclusions: In the largest study of real-world patients receiving LCS to date, adherence to Lung-RADS recommendations is lower than previously observed in clinical trials. Our results highlight the need for further study of system-level mechanisms to improve longitudinal LCS adherence rates.[Table: see text]
Global tissue stiffness on breast MR elastography: High-risk dense breast patients have higher stiffness compared to average-risk dense breast patients.
Authors: Patel Bhavika K. , Pepin Kay , Brandt Kathy R , Mazza Gina L. , Pockaj Barbara A. , Chen Jun , Zhou Yuxiang , Northfelt Donald W. , Anderson Karen , Ernst Brenda , Cronin Patricia , Ahmad Sarwat , Kling Juliana , Millstine Denise , Apsey Heidi , Vachon Celine M , Nelson Ilyse , Ehman Richard
Published: June 2021

10541

Background: Biomechanical tissue properties may vary in the breasts of patients at elevated risk for breast cancer. We aim to quantify in vivo biomechanical tissue properties in various breast densities and in both normal risk and high risk women using Magnetic Resonance Imaging (MRI)/MRE and examine the association of biomechanical properties of the breast with cancer risk. Methods: In this IRB–approved prospective single-institution study, we recruited two groups of women differing by breast cancer risk to undergo a 3.0 T dynamic contrast enhanced MRI/MRE of the breast. Low-average risk women were defined as having no personal or significant family history of breast cancer, no prior high risk breast biopsies and a negative mammography within 12 months. High-risk breast cancer patients were recruited from those patients who underwent standard of care breast MR. Within each breast density group (non-dense versus dense), two-sample t-tests were used to compare breast stiffness, elasticity, and viscosity across risk groups (low-average vs high). Results: There were 50 low-average risk and 86 high-risk patients recruited to the study. The risk groups were similar on age (mean age = 55.6 and 53.6 years), density (68% vs. 64% dense breasts) and menopausal status (66.0% vs. 69.8%). Among patients with dense breasts, mean stiffness, elasticity, and viscosity were significantly higher in high risk patients ( N = 55) compared to low-average risk patients ( N = 34; all p < 0.001). In the multivariate logistic regression model, breast stiffness remained a significant predictor of risk status (OR=4.26, 95% CI [1.96, 9.25]) even after controlling for breast density, MRI BPE, age, and menopausal status. Similar results were seen for breast elasticity (OR=4.88, 95% CI [2.08, 11.43]) and viscosity (OR=11.49, 95% CI [1.15, 114.89]). Conclusions: Structurally-based, quantitative biomarker of tissue stiffness obtained from global 3D breast MRE is associated with differences in breast cancer risk in dense breasts. As such, tissue stiffness could provide a novel prognostic marker to help identify the subset of high-risk women with dense breasts who would benefit from increased surveillance.[Table: see text]
Understanding factors associated with uptake of lung cancer screening among individuals at higher risk.
Authors: Gudina Abdi , Cupertino Anapaula , Kamen Charles Stewart , Adler David , Belcher Elizabeth , Gilmore Nikesha , Kleckner Amber , Arana Evelyn , Kehoe Lee , Hardy Sara , Janelsins Michelle Christine , Morrow Gary R.
Published: June 2021

10559

Background: Lung cancer is the leading cause of cancer death in the U.S, accounting for about 25% of all cancer mortality. The U.S Preventive Services Task Force has recommended annual screening for lung cancer using low-dose computed tomography (LDCT) scanning for individuals at higher risk (aged 55-80 years with a >30 pack-year smoking history). Early detection using LDCT scanning reduces lung cancer specific mortality by 20%. Despite its efficacy, the uptake of annual lung cancer screening among high-risk individuals remains low ( < 18%). The purpose of this study was to identify factors associated with the uptake of lung cancer screening in high-risk individuals in the U.S population. Methods: Data for this study were obtained from the 2017-2019 Behavioral Risk Factor Surveillance System (BRFSS), a population-based survey conducted annually by the Centers for Disease Control and Prevention (CDC) in collaboration with health departments in all 50 states, Washington, DC, and the U.S territories. We restricted our sample to high-risk individuals aged 55-80 years with a >30 pack-year smoking history. Only subjects with complete data on all predictor variables (age, gender, race/ethnicity, marital status, education, income, insurance, COPD, current smoking status, primary care provider) and the outcome variable (uptake of lung cancer screening) (n = 11, 714) were included in the final analysis. Chi-square tests were used to compare the uptake of lung cancer screening by demographic and socioeconomic factors. Multivariable logistic regression models were used to model the association between the predictors and the outcome variable. Results: Individuals with no health insurance (OR: 0.64; 95%CI: 0.46-0.90), no primary healthcare provider (OR: 0.40; 95%CI: 0.31-0.52), no chronic obstructive pulmonary disease (COPD) (OR: 0.35; 95%CI: 0.31-0.0.40) and who were females (OR: 0.86; 95%CI: 0.76-0.96) were less likely to participate in annual lung cancer screening. Individuals aged 65–69 years (OR: 1.65; 95%CI: 1.38-1.97), 70–74 years (OR: 1.77; 95%CI: 1.46-2.14) or 75–80 years (OR: 1.42; 95%CI: 1.16-1.76) were more likely to receive annual lung cancer screening compared with those aged 55-59 years. Race/ethnicity, level of education, level of income, marital status, and current smoking status had no significant association with the uptake of annual lung cancer screening. Conclusions: Our study identifies factors associated with lower uptake of annual lung cancer screening (no health insurance coverage, no primary healthcare provider, no COPD, and female gender). The findings from this study have important implications for the design of more effective interventions to target specific subgroups for the uptake of annual lung cancer screening.
Trends in breast cancer incidence among young women aged 20 to 49 years in the United States.
Authors: Xu Shuai , Han Yunan , Wan Fei , Toriola Adetunji T.
Published: June 2021

10573

Background: Breast cancer in young women is diagnosed at more advanced stages and has a less favorable prognosis. We investigated trends in breast cancer incidence by race/ethnicity, hormone receptor status, and tumor stage in women aged 20-49 years over the past 25 years, as well as the impact of period and cohort effects on these trends. Methods: We used data from Surveillance, Epidemiology, and End Results (SEER) 13 registries for 1993-2002 and SEER 18 registries for 2003-2017. We calculated age-standardized incidence rates and annual percent change (APC), and stratified by race/ethnicity, hormone receptor status (estrogen receptor [ER] and progesterone receptor [PR]), and tumor stage (I-IV) for 222,424 women aged 20-49 years with a primary invasive breast cancer. We performed age-period-cohort analysis (presented as incidence rate ratios [IRR]) to investigate the effects of age, period, and cohort on incidence trends using the 1948 cohort and 1993-1997 period as the reference groups, respectively. Results: Between 2010-2017, invasive breast cancer incidence increased (APC = 0.67%, 95%CI: 0.32 to 1.03) among women aged 20-49 years, after being stable from 1993-2010. There were differences by race over the 25-year period (1993-2017). We observed significant increases in incidence among non-Hispanic White (NHW) (APC = 0.25%, 95%CI: 0.16 to 0.34), non-Hispanic Asia/Pacific Islander (NHAPI) (APC = 0.58%, 95%CI: 0.34 to 0.82), and Hispanic women (APC = 0.59%, 95%CI: 0.34 to 0.83), but not among non-Hispanic black (NHB) women (APC = 0.14%, 95%CI: -0.06 to 0.34). Incidence increased for ER+ tumors but decreased for ER- tumors: ER+/PR+ (APC = 2.39%, 95%CI: 2.20 to 2.58), ER+/PR- (APC = 1.46%, 95%CI: 1.05 to 1.87), ER-/PR+ (APC = -6.33%, 95%CI: -7.31 to -5.33), and ER-/PR- (APC = -0.70%, 95%CI: -1.09 to -0.32). The decrease in ER-/PR- tumors appeared largely driven by decreases among HNW women. Incidence for stages I (APC = 0.31, 95%CI: 0.07 to 0.55), II (APC = 0.99, 95%CI: 0.82 to 1.16), and IV (APC = 2.88, 95%CI: 2.37 to 3.39) tumors increased while that for stage III tumors decreased (APC = 0.81%, 95%CI: -1.04 to -0.59). Both the cohort and period effects impacted incidence, with the cohort effect almost 10 times larger than the period effect. Age-specific relative risk by birth cohort initially decreased between 1948 and 1958 but steadily increased from 1958 to 1993. Breast cancer incidence was higher among women born in the 1988 (IRR = 1.17, 95%CI: 1.07 to 1.28) and 1993 (IRR = 1.22, 95%CI: 0.99 to 1.51) cohorts than for those born in 1948 cohort. Conclusions: Breast cancer incidence is increasing among young women, mainly driven by increases in ER+ tumors. Prevention efforts need to focus on how we can address factors driving the increase in ER+ tumors and also learn from what has worked for decreasing ER- tumors.
Hereditary cancer testing in an ethnically diverse U.S. population.
Authors: Basiliere Michele , Woods Stephanie , Owen Heidi , Dohany Lindsay , McDaniel Lisa , Wisniewski Nicholas
Published: June 2021

10579

Background: The clinical utility of hereditary cancer multigene testing is well-established. Most testing has been performed in the White European population, with a relative shortage of data in other ethnic groups. Evaluation of hereditary cancer variants within diverse ethnic populations is important to drive accurate variant interpretation. This study aims to review the outcomes of hereditary cancer testing in an ethnically diverse U.S. population. Methods: We conducted a retrospective analysis of 8,888 test results from a 31-gene hereditary cancer test using next-generation sequencing with copy number variant analysis. Results were separated into seven categories based on the ethnicity selected on the test requisition: African American (AA), Asian (A), Ashkenazi Jewish (AJ), Hispanic (H), White (W), Other (O), and Unknown (U). O was used for any handwritten ethnicity or if multiple ethnicities were selected and U if no ethnicity was chosen. We quantified the number of negative, positive (pathogenic or likely pathogenic (P/LP) variant) and variant of uncertain significant (VUS) results for each ethnic group. We tallied the gene and variant for each result with a positive, negative or VUS. We used a Fisher's Exact test and Bonferroni-adjusted p-values to account for multiple hypothesis testing. Results: Of the 8,888 orders reviewed, 45% were non-White ethnic groups. The P/LP variant rate was lower for AA (4%, p=2e-04) compared to W (9%). The VUS rate was higher for O, AA and A (48%, 56%, and 57%; p=0.0045, 3.1e-17 and 4.8e-06, respectively), compared to 38% in W. Lower negative rates were found in A and AA (37% and 40%; p=0.00024 and 9.4e-10, respectively), and trending lower in O (46%, p=0.0097), compared to 58% for W. The VUS rate for H is 41% (p value = 0.095). Conclusions: Our results suggest that non-Whites may be at a disadvantage when it comes to hereditary cancer multigene testing due to the higher rate of VUS results. The inverse correlation between the overall rates of VUS and negative results when comparing these populations suggests there may be limited variant information for the non-White population in medical literature and available databases. This underrepresentation may make it more difficult to accurately characterize a variant. Despite the small sample size, these findings are consistent with previous publications; however, gene specific outcomes could not be evaluated. This finding suggests that providers could give these patients uninformative results more often, which has potential to impact screening protocols for these families. More research is needed to understand the impact of variant classification across ethnicities to decrease health disparities.
Variant reclassification and its impact on clinical care in an Asian cancer center.
Authors: Chiang Jianbang , Chia Tze Hao , Chan Sock Hoai , Ngeow Joanne YY
Published: June 2021

10583

Background: Genetic testing has demonstrated clinical utility in the identification and subsequent surveillance of patients with cancer predisposition syndromes. However, the increased likelihood of encountering a variant of uncertain significance (VUS) in individuals of non-European descent such as Asians may be challenging to both clinicians and patients in interpretation and management. VUS can be reclassified as more data becomes available. VUS reclassification is important, as it may have implications for surveillance and treatment. This study aims to evaluate the prevalence and patterns of variant reclassification in an Asian country and its impact on patient management. Methods: A prospective cohort of patients seen at the Cancer Genetics Service at the National Cancer Center Singapore between February 2014 to March 2020 was evaluated. The frequency, direction and time to variant reclassification was assessed by comparing the reclassified report against the original report. Results: A total of 1412 VUS were reported in 49.9% (845/1695) of patients. Over six-years, 6.7% (94/1412) of variants were reclassified. Most VUS (94.1%; 80/85) were downgraded to benign/likely benign variant, with a smaller proportion of VUS (5.9%; 5/85) upgraded to pathogenic/likely pathogenic variant. Actionable VUS upgrades and pathogenic/likely pathogenic variant downgrades, that resulted in management changes, happened in 31.0% (39/126) of patients. The median and mean time taken for reclassification were 1 and 1.62 year(s) respectively. Conclusions: Clinicians need to put in place a system for review of variants, as variant reclassification can lead to changes in management in nearly 1/3 of patients. Management should be based on the patient’s personal history, family history and variant interpretation. We propose a clinical guideline to standardize management of patients with VUS. For clinically relevant or suspicious VUS, follow-up is recommended every two years, as actionable reclassifications may happen during this period.
Evaluation of cohort diversity in development and validation studies of hereditary cancer genetic risk assessment models.
Authors: Gammon Amanda , Khan Ambreen , Jeter Joanne M.
Published: June 2021

10600

Background: Multiple models estimate a person’s chance of harboring a pathogenic variant increasing cancer risk. Some pathogenic variants are more common in individuals from specific ancestries, such as the BRCA1 and BRCA2 founder variants in Ashkenazi Jews. Yet data remains limited on the larger variant spectrum seen among people of different ancestral backgrounds and whether or not the pathogenic variant frequency differs in many populations. Due to this, it is important that genetic risk assessment models be validated in a diverse cohort including Black, Indigenous, People of Color (BIPOC). Methods: A literature search was conducted to identify published development and validation studies for the following genetic risk assessment models: BRCAPRO, MMRPRO, CanRisk/BOADICEA, Tyrer-Cuzick, and PREMM. Validation studies that only evaluated the cancer risk prediction capabilities of the models (and not the genetic variant risk prediction) were excluded. The following participant information was abstracted from each study: total number of participants, gender, race, and ethnicity. Authors were contacted to obtain missing information (if available). Results: 12 development and 12 validation studies of the genetic risk assessment models BRCAPRO, MMRPRO, CanRisk/BOADICEA, Tyrer-Cuzick, and PREMM were abstracted. Of the validation studies, five were internal validation studies conducted by the model developers, and seven were external validation studies. Four external validation studies compared multiple models. 75% (18/24) of papers did not include reporting of participant race or ethnicity information in their published reports. External validation studies (4/7, 57%) more often reported participant race/ethnicity than development (0/12, 0%) or internal validation (2/5, 40%) studies. The external validation studies for BRCAPRO reporting race/ethnicity information involved cohorts that ranged from 50-51% non-Ashkenazi Jewish white, 28% African American, 1% Asian, 2-49% Hispanic, and 19-42% Ashkenazi Jewish. The external validation studies for MMRPRO and PREMM reporting race/ethnicity information involved cohort that ranged from 0-82% white, 4-100% Asian, 7% Black, and 7% Hispanic. Conclusions: Increased reporting of participant ancestry and ethnicity is needed in the development and validation studies of genetic risk assessment models. BRCAPRO’s validation cohorts have included a higher percentage of Hispanic and Black/African American participants, while MMRPRO and PREMM have been validated in a higher percentage of Asian participants. As debate continues about the utility of currently used racial categories in genetics research, it will be important to determine how best to report on participant diversity. These findings highlight the continued need for genetics researchers to engage BIPOC and identify ways to diversify their participant cohorts.
Stereotactic radiosurgery (SRS) for brain metastasis (BM) in hormone receptor positive (HR+) HER2 negative breast cancer (BC).
Authors: Singareeka Raghavendra Akshara , Gao Chao , Wang Fuchenchu , An Ran , Wang Yan , Suki Dima , Heimberger Amy B. , Tripathy Debu , Li Jing , Ibrahim Nuhad K.
Published: June 2021

1069

Background: With the increase of the utilization of SRS for the treatment of oligometastatic BM over surgical reaction or whole brain radiation therapy (WBRT), we sought to evaluate the impact of SRS on overall survival in HR+Her2- BC and prognostic factors associated with SRS. Methods: We reviewed prospectively collected data in the electronic data bases of the breast medical, surgical and radiation oncology departments at MD Anderson cancer center. We aimed at identifying HR+HER2- BC patients who received upfront SRS for BM’s between 08/10/2009 and 02/27/2018.Overall survival was defined as the time from the first SRS to last follow-up/death. Multivariate analysis by the Cox proportional hazards regression analysis was performed to evaluate the prognostic factors (age at BM, stage, Karnofsky performance score (KPS), symptomatic BM, BM at 1stdistant metastatic presentation, extracranial Disease, treatment history, salvage therapy, number of brain lesion treated) of SRS that influenced survival. Results: A total of 125 patients were identified, and we are reporting on 68 with completed analysis. Median age at time of first SRS was 53.86 years. 51 patients of the 68 were deceased at the time of this analysis and 17 patients were alive at the time of last follow-up. 49 patients (72.06 %) presented with radiation necrosis after SRS; 36 patients (52.94 %) presented with BM as 1st distant metastasis including metastasis to other sites. Number of BM’s lesions <4 was 60 (88.2%) and >=4 was 7 (10.3%). The median follow-up from time of first SRS for survivors was 10.84 months. 24 (35.29%) received two or more sessions of SRS and the mean time between first and second SRS sessions for these patients was 14.24 months. Median time from first SRS to second SRS for ER+HER2− patients was 10.84 months (n = 24); on multivariable analysis, higher Karnofsky performance score (KPS) was associated with better survival compared to no salvage therapy. Patients with KPS>90 (p=0.005) had better survival and reduced the hazard by a factor of 0.33 (or 67%). Receiving SRS (p=0.0003) or SRS+WBRT (0.0001) as salvage therapy reduced the hazard (risk of death) by 86% and 85%, respectively. Conclusions: SRS is an effective treatment modality for HR+HER2- BM from BC. Patients who received SRS or SRS and WBRT, KPS >90 had better survival than patients who didn’t receive any salvage therapy. Updated data will be available at the time of the presentation.[Table: see text]
Decreased enrollment of patients with advanced lobular breast cancer compared to ductal breast cancer in interventional clinical trials.
Authors: Abel Mary Kathryn , Melisko Michelle E. , Rugo Hope S. , Chien Amy Jo , Diaz Italia , Levine Julia K. , Griffin Ann , McGuire Joseph , Esserman Laura , Borno Hala , Mukhtar Rita A.
Published: June 2021

1092

Background: Response Evaluation Criteria in Solid Tumors (RECIST) criteria are often used to measure tumor response in cancer trials, especially in the stage IV setting. However, RECIST requires measurable disease, which is less common in invasive lobular breast carcinoma (ILC) of the breast, a diffusely growing tumor type, compared to invasive ductal carcinoma (IDC). We examined the prevalence of RECIST in breast cancer clinical trials, and whether there are differential trial enrollment rates by histology and stage. Methods: We analyzed the clinicaltrials.gov database to evaluate the proportion of interventional, stage IV clinical trials that require measurable disease as inclusion criteria or outcome measures. We then performed an institutional cohort study comparing the proportion of patients in the University of California, San Francisco (UCSF) OnCore clinical trials management system (CTMS) to the UCSF Cancer Registry between 2000-2018, stratified by histology and stage. We hypothesized that the proportion of patients with ILC in the CTMS would be significantly lower than in the cancer registry. Results: There were 146 actively-recruiting, interventional clinical trials for stage IV breast cancer that were identified in our search on clinicaltrials.gov. Overall, 108 (74%) required measurable disease for study participation. The UCSF Cancer Registry included 8,679 patients, while the UCSF OnCore CTMS included 1,511 patients (Table). In those with early stage disease, where RECIST is not typically used, there was no difference in the proportion of ILC patients enrolled in clinical trials versus in the cancer registry. However, among those with stage IV disease, there was a significantly lower proportion of patients with ILC in the CTMS than in the cancer registry (9.2% versus 17.9%, p = 0.005). In contrast, patients with stage IV IDC were overrepresented in the clinical trials database compared to the cancer registry. Conclusions: Patients with metastatic ILC were significantly less likely to be enrolled in clinical trials than those with metastatic IDC. This decreased enrollment may be due to the widespread use of RECIST, and further investigation is needed to ensure equity in access to clinical trials.[Table: see text]
Efficacy of a fully remote primary lecture series at an academic hematology and oncology fellowship program.
Authors: Ghanem Sassine , Harewood Janine Claudia Khadija , Yee Jia-Llon , Campbell Jimenez Brian , Gonsky Jason Parker
Published: June 2021

11031

Background: 615 fellows began training in American combined hematology/oncology fellowship programs in July 2020. These new fellows face a steep learning curve. The coronavirus pandemic has significantly affected how we learn, with programs having to convert most collective learning to a completely virtual format. Research on the efficacy of introductory lecture series in academic hematology/oncology programs is limited especially regarding virtual formats. We introduced a virtual introductory lecture series with the goal of increasing the clinical confidence and knowledge base of first-year fellows. Methods: A once weekly remotely-delivered two-hour primer series was designed with lectures given by both third-year fellows and faculty from July-August 2020. Fellows were asked to complete pre & post-test evaluations of each lecture. Evaluations included a combination of knowledge-based questions & self-reported confidence assessment. Results: 14 fellows were assigned pre- and post-tests in the study. 1 fellow was excluded due to lack of participation. A total of 123 paired pre and post-tests were compared. Data analysis was performed with SPSS v 24.0 using the paired samples t-test. Pre and post-tests were graded on a scale of 0-100. The pre to post mean difference compares the mean test result of the post tests to that of the corresponding pretests. Questions were divided into 2 groups. The 1st group tested the fellow’s medical knowledge regarding the pathology while the 2nd group tested the comfort in the management, diagnosis and treatment. In the statistical analysis, these questions were defined as “Knowledge” and “Comfort” accordingly, the sum as “Complete”. A statistically significant improvement in post-test knowledge for fellows of all years was noted with a pre to post test mean difference of 12.52, P <.0001. The difference was more pronounced among 1st year fellows with a pre to post test mean difference of 16.84, P <.0001. A similar improvement was seen for the comfort in management questions. The post-test comfort pre to post test mean difference was 10.48, P <.0001 for fellows of all years and 6.70, P <.0001 for first year fellows. Conclusions: A remotely-delivered introductory lecture series for fellows in a hematology/oncology training program increases both clinical knowledge and clinical confidence in fellows of all years of training.[Table: see text]
NCI protocol 10250: A phase II study of temozolomide and olaparib for the treatment of advanced uterine leiomyosarcoma.
Authors: Ingham Matthew , Allred Jacob B. , Gano Katherine , George Suzanne , Attia Steven , Burgess Melissa Amber , Seetharam Mahesh , Boikos Sosipatros Alexandros , Bui Nam , Chen James Lin , Close Julia Lee , Cote Gregory Michael , Thaker Premal H. , Ivy S. Percy , Das Biswajit , Shapiro Geoffrey , Kochupurakkal Bose , Trepel Jane B. , Pommier Yves , Schwartz Gary K.
Published: June 2021

11506

Background: Uterine leiomyosarcoma (uLMS) is an aggressive sarcoma subtype with frequent metastatic relapse. After failure of front-line chemotherapy, remaining options provide limited benefit (trabectedin: ORR 11%, mPFS 4.0 mos; pazopanib: ORR 11%, median PFS 2.9 mos; dacarbazine: ORR 9%, mPFS 1.5 mos). Recent molecular studies suggest uLMS harbors characteristic defects in the homologous recombination (HR) DNA repair pathway, including somatic biallelic BRCA2 deletion in 10%, implicating potential sensitivity to PARP-inhibitor based treatment approaches. In preclinical uLMS models in which temozolomide (T, an oral equivalent to dacarbazine) or the PARP inhibitor olaparib (O) showed limited single agent activity, the combination of T + O was highly effective in inhibiting uLMS tumor growth and promoting apoptosis. Methods: NCI protocol #10250 is a single-arm, open-label, multi-center phase II study evaluating T + O in advanced uLMS. Pts had progression on ≥ 1 prior line and ECOG PS ≤ 2. Pts received T 75 mg/m2 PO daily + O 200 mg PO BID days 1-7 in 21-day cycles. Primary endpoint was ORR. A one-stage binomial design was used. If ≥ 5/22 responded, the treatment was considered promising (95% power; α = 0.06). All pts underwent paired tumor biopsies. Correlative assays to evaluate for HR deficiency (whole exome sequencing/RNAseq, RAD51 foci formation) and for intrinsic PARP inhibitor resistance (SLFN11 expression) will be correlated with response. Results: 22 patients were evaluable (median age 55, median prior treatment lines 3). Median follow-up was 10.8 mos. Primary endpoint, ORR within 6 mos of initiating treatment, was 23% (5/22). Overall ORR was 27% (6/22). Median PFS was 6.9 mos (95% CI: 5.4 mos – not estimable (NE)). Median duration of response (DOR) was 12.0 mos (95% CI: 9.5 mos – NE). Hematologic toxicity was common (grade 3/4 neutropenia, 77%; thrombocytopenia 32%) but manageable with dose modification. Correlative assays are ongoing with plans to present at the meeting. An immunohistochemical assay for RAD51 foci has been adapted for uLMS samples and clearly distinguishes BRCA2- deleted and wild-type tumors. Conclusions: NCI 10250 met the prespecified primary efficacy endpoint of ORR in a population of patients with heavily pre-treated uLMS. Responses are durable (median DOR 12 mos). Correlative assays are being completed to evaluate whether uLMS tumors with HR deficiency or with preserved SLFN11 expression are most sensitive to T + O and may underlie durable responses. A randomized study of the combination is planned. Clinical trial information: NCT03880019.
Updated results of European Organization for Research and Treatment of Cancer (EORTC) phase 2 trial 1202 cabazitaxel in patients with metastatic or inoperable locally advanced dedifferentiated liposarcoma.
Authors: Sanfilippo Roberta , Hayward Richard L , Musoro Jammbe , Benson Charlotte , Leahy Michael Gordon , Brunello Antonella , Blay Jean-Yves , Steeghs Neeltje , Desar Ingrid , Ali Nasim , Hervieu Alice , Thway Khin , Marreaud Sandrine , Litiere Saskia , Kasper Bernd
Published: June 2021

11518

Background: Treatment options for patients with unresectable and/or metastatic dedifferentiated liposarcoma (DDLPS) are limited. The most effective agents include doxorubicin, ifosfamide, trabectedin and eribulin, but, in general, objective response rates (ORR) and progression free survival (PFS) are modest. Cabazitaxel exerts its effect through inhibition of microtubular disassembly and has been shown to be relatively safe, effective and well-tolerated. EORTC 1202 assessed whether cabazitaxel demonstrated sufficient antitumor activity in patients with metastatic or inoperable locally advanced DD LPS to justify further investigation in a phase III setting. Methods: This was an international multi-center, open label single arm phase II trial. The clinical cut-off date for the primary analysis was performed on August 31, 2020. Data base lock was performed on February 2, 2021. Eligible patients with metastatic or inoperable locally advanced DD LPS, after a centralized pathological review, were treated with cabazitaxel 25mg/m² IV infusion over 1 hour every 21 days. Primary endpoint was PFS rate at 12 weeks assessed by local investigator per RECIST 1.1. Based on a Simon two-stage design, at least 4 out of 17 (Stage 1) and 11 out of 37 (Stage 2) eligible and evaluable patients who are progression-free at 12 weeks were needed. Currently, a centralized radiological assessment is ongoing. Results: Forty patients were registered by 10 institutions in 4 countries between March 2015 and March 2019, with 2 patients being ineligible. One patient was still on treatment at the clinical cut-off date. The number of cycles ranged from 1 to 30, with a median of 5; 26 patients (65%) received at least 4 cycles of cabazitaxel. PFS at 12 weeks was 55% (conditional 1-sided 95% CI 40.8-100), achieving the primary study endpoint. The median FU was 21.6 months, median PFS was 6 months and median OS 21 months. RR was 8% with one CR and two PR. Twenty-three(60.5%) pts had a SD. Disease control (PR+SD) was achieved in 26 patients (68%). The most common cabazitaxel -related grade >3 adverse events in all 40 registered patients were Neutrophil count decreased (50%), febrile neutropenia (25%), fatigue (12.5%), and anemia (10%). There were no cabazitaxel-related deaths. Conclusions: EORTC 1202 met its primary endpoint, with 21/38 pts (55%) being progression-free at 12 weeks. Results of this trial confirm activity of cabazitaxel in patients with metastatic or inoperable locally advanced DD LPS and looks interesting if compared to the other available options and experimental drugs recently reported in this patient population. Clinical trial information: NCT01913652.
Efficacy and safety of anlotinib plus TQB2450 in patients with advanced soft tissue sarcoma: A multicenter, single armed, phase 1b trial.
Authors: Liu Jiayong , Fan Zhengfu , Guo Wei , Gao Tian , Li Shu , Xu Jie , Bai Chujie , Xue Ruifeng , Zhang Lu , Xie Lu , Tan Zhichao
Published: June 2021

11547

Background: Anlotinib, a multitargeted tyrosine kinase inhibitor, had been prove to be effective for the treatment of advanced or metastatic soft tissue sarcoma(STS) faild anthracycline chemotherapy. With the lack of prospective data of combination of PDL-1 inhibitor and antiangiogenic agent, we designed a phase 1b study to investigated the efficacy and safety of anlotinib plus TQB2450 in patients with STS. Methods: Eligible patients (age 18-70, ECOG 0-1, with histopathologically confirmed advanced STS, at least one measurable lesion according to RECIST 1.1, and previously received front-line anthracycline chemotherapy) were included and received anlotinib (12mg qd, D1-14, 21d/cycle) plus TQB2450 (1200 mg, IV, D1, 21d/cycle) until disease progression or intolerable toxicities.The primary endpoint was objective response rate (ORR), secondary endpoints included safety, overall survival (OS), progression-free survival (PFS), disease control rate (DCR). Results: From January 2019 to January 2021, 30 pts were enrolled1, 12 alveolar soft part sarcoma and 18 others (7 synovial sarcoma, 4 leiomyosarcoma, 5 undifferentiated pleomorphic sarcoma, 1 fibrosarcoma and 1 epithelioid sarcoma). ORR by RECIST was 36.7%, DCR was 83.3%, 11/30 pts had PR, 14/30 (46.7%) had SD, 5/30 (16.7%) PD. Median PFS was 9.6 m in all pts and 4.9m. in non-ASPS, respectively. Median OS in non-ASPS was 10.27m, while mOS in all pts and both mPFS and mOS in ASPS had not been reached. Notably, to ASPS pts, ORR was 75%, and DCR was 100%. The most common 1-2 grade treatment-related adverse reaction (TRAE) was hypothyroidism (19/30,63.3%)，hypercholesterolemia (16/30, 53.3%) and hypertriglyceridemia (16/30, 53.3%), the most common ≥3 grade TRAEs were hypertriglyceridemia (3/30, 10%). 6 SAE (20%) occurred, including 2 pneumothorax, 1 Immune associated hapatic injury, 1 hypotension, 1 Immune myocarditis and 1 diabetic ketoacidosis. Conclusions: The combination of anlotinib and TQB2450 showed promising activity in second-line treatment of advanced STS, especially in ASPS, with well tolerance and acceptable toxicity.
A pilot study of the feasibility and utility of a fitness tracker to correlate activity level with patient reported outcomes (PROs) in sarcoma patients undergoing systemic therapy.
Authors: Davis Elizabeth J. , Ayers G. Dan , Wallace Deborah , Kaiser Elizabeth , Keedy Vicki Leigh , Agarwal Rajiv
Published: June 2021

11559

Background: The feasibility and utility of wearable devices is unknown in sarcoma patients (pts). Objective assessment of activity level, body composition, and PROs facilitate understanding of the tolerability and toxicity of cancer treatment. Methods: From 6/11-10/12/2020, we enrolled sarcoma pts receiving systemic therapy to a prospective study evaluating activity levels and sleep via a Fitbit Charge 3, body composition with the Inbody 570, and PROs using NIH PROMIS short forms (fatigue, pain, physical function, and sleep disturbance), the Generalized Anxiety Disorder Scale, and the Patient Health Questionnaire Depression Scale. Time on study was 12-16 weeks depending upon treatment. The Fitbit was worn continuously. Body composition and PROs were assessed every 3-4 weeks. Feasibility was defined as successful device wearing and data syncing. Data was collected through a cloud-based application, Fitabase. Results: 22 pts were approached and enrolled. Two pts did not complete the first study assessment due to disease progression and were excluded from analysis. 50% of pts were female. 90% of pts were white. Median age was 47 yrs (range 20-81). The most common histologies were Ewing sarcoma and leiomyosarcoma. 89.5% (17/19) of pts wore the Fibit for >3 weeks; median time was 68 days (5-112). 95% (19/20) of pts were able to sync data. Median step count was 2614 steps (376-19806). High step counts, defined as greater than the median, were associated with improved sleep (p=0.14) and physical function (p=0.22), and decreased pain (p=0.15), but these associations were not statistically significant. Low step counts, defined as lower than the median, were associated with skeletal muscle mass loss (p=0.22), but this was not statistically significant. Conclusions: Incorporating a fitness tracker is feasible in sarcoma pts receiving systemic therapy. It provides longitudinal, objective evaluation of activity levels and sleep patterns. Correlation of activity level with sleep, body composition, and PROs was limited due to small numbers; however, a larger prospective pilot study is ongoing.[Table: see text]
A patient reported outcomes of treatments for desmoid tumors: An international natural history study.
Authors: Braggio Danielle , Lucas Amanda , Hernandez Lynne , Mercier Kelly
Published: June 2021

11560

Background: The Desmoid Tumor Research Foundation (DTRF) launched the natural history study (NHS) in 2017. At this time, there are no standard-of-care options for this rare sarcoma. The treatments, clinical descriptors, and the patient reported outcomes to pharmacologic agents are described here within. Methods: The web-based natural history study launched September 2017 in collaboration with the National Organization of Rare Disorders. It contains 15 surveys covering diagnostics, disease, treatment, care management, and quality of life. Treatment types included in the DTRF NHS were pharmacology, surgery, radiation, high-intensity focused ultrasound (HiFU), and active surveillance (watch and wait). Results: While surgery was once the primary intervention for desmoid tumor patients, the NHS participants reported that 47.6% had received active surveillance or no systemic treatment at diagnosis. This is most common for desmoid tumors located in abdominal wall (54/103; 52.4%). There were 87 reported cases of complete surgical resection, 38 incomplete resections, and 23 bowel resections. 9 amputations were reported; 8 participants reported recurrent disease following the removal of the limb. The non-surgical interventions, such as radiation and HiFU, were mostly described for participants with chest wall tumors (15 pts) and joints/extremities (10 pts). Many options for systemic therapies were described including sorafenib (44/284; 15.5%), sulindac (36/284; 12.7%), and anti-hormonal agents tamoxifen and toremifene (34/285; 10.9%) were described. Targeted agents, such as gamma secretase inhibitor, pazopanib, and sorafenib, were greater in the United States than the non-US country participants (21% vs 9%). Multiple lines of treatments were reported by 81 participants, surgery is greatest as the first intervention for all tumor locations (49/81, 60%), with the exception of those with head/neck tumors who received chemotherapy (6/11, 55%). Analysis has started to evaluate the efficacy of systemic treatments from these NHS data. The table describes the participant reported outcomes of anti-hormonal agents, chemotherapeutics, non-steroidal anti-inflammatories, and targeted agents. Both chemotherapies and targeted agents were reported to have 38.1% response rates from the participants with 34.3% and 23.8% of participants reported progressive disease on therapy, respectively. Conclusions: Desmoid tumor NHS study participants reported the use of many treatment modalities demonstrating a range of frequency of use by tumor location and efficacy. Data collection through the DTRF NHS is ongoing.[Table: see text]
Palbociclib (P) in patients (pts) with soft tissue sarcoma (STS) with CDK4 amplification: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.
Authors: Schuetze Scott , Rothe Michael , Mangat Pam K. , Garrett-Mayer Liz , Meric-Bernstam Funda , Farrington Laura Catherine , Calfa Carmen , D'Andre Stacy D. , Livingston Michael B. , Thota Ramya , Marr Alissa S. , von Mehren Margaret , Wentzel Kristopher , Schilsky Richard L.
Published: June 2021

11565

Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of STS pts with CDK4 amplification treated with P are reported. Methods: Eligible pts had advanced STS, no standard treatment options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received P at 125 mg orally once daily for 21 days, followed by 7 days off until disease progression. Pts matched to P had CDK4 amplification and no RB mutations. Simon 2-stage design tested the null disease control (DC) - defined as partial (PR), complete response (CR) or stable disease at 16+ weeks (SD 16+) - rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: 29 pts (66% male) with STS with CDK4 amplification were enrolled from July 2016 to Nov 2019. 1 pt was not evaluable and excluded from efficacy analyses. Demographics and outcomes are summarized in Table. One pt with partial response (PR) and 12 pts with SD16+ were observed for DC and objective response (OR) rates of 48% (95% CI: 31%, 62%) and 3.7% (95% CI: 0.1%, 19%), respectively, and the null DC rate of 15% was rejected (p<0.001). 9/13 pts with DC continued on treatment for >32 weeks. 14 pts had at least one grade 3-4 AE at least possibly related to P with the most common being low WBC/platelets. Other grade 3 AEs included increased alanine aminotransferase, anemia, and fatigue. Conclusions: Monotherapy P demonstrated anti-tumor activity in heavily pre-treated pts with STS with CDK4 amplification. Additional study is warranted to confirm the efficacy of P in pts with STS with CDK4 amplification. Clinical trial information: NCT02693535. [Table: see text]