bluuebunny/crossref_metadata_2025 huggingface dataset:
68Ga-HER2 affibody PET/CT imaging as an option in patients whose HER2 status of any tumor in the body needs to be deciphered.
Authors: Miao Haitao , Sun Yuyun , Hu Xichun , Song Shaoli , Zhang Jian
Published: June 2021

1045

Background: Anti-HER2 targeted agents are standard of care for HER2 positive patients with either early or advanced breast cancer. Determination of tumor HER2 status helps diagnosing and treating breast cancer. In any tumor which required this biological information, we used a novel 68Ga-NOTA-MAL-MZHER2 (68Ga-HER2) affibody PET/CT to differentiate HER2 status of each lesion in the patient body. Methods: 68Ga-HER2 affibody PET/CT was performed in breast cancer patients if HER2 status of any lesions in the patient body remained to be determined. Results: Twenty-four patients were enrolled. 68Ga-HER2 affibody PET/CT was requested by physicians due to the following reasons: 6 with multiple primary cancers (including patients who harbored two primary breast malignancies but with different HER2 status, and patients who had at least another non-breast primary other than HER2-positve breast cancer), 13 with metastases inaccessible for biopsy or repeated biopsy, 6 with inconsistent HER2 status between the primary and metastatic lesions, and 4 with different HER2-status within metastases (ICH ranging from 0-3+). Assessment report showed that the 68Ga-HER2 affibody tumor uptake was considered positive in 16 patients, negative in 7 patients, and equivocal in one patient. In 11 lesions which was pathological-confirmed HER2-positivity, 100% of the tumors were also positive with this PET/CT. The heterogeneity of 68Ga-HER2 affibody uptake was obvious, with a maximal 8.5-fold difference within one patient and a maximal 11-fold difference among patients. Conclusions: 68Ga-HER2 affibody PET/CT imaging is a valuable tool if HER2 status of any tumor needs to determined. We are now evaluating the 68Ga-HER2 affibody PET/CT imaging as a non-invasive approach to classify the molecular subtype of metastatic breast cancer, and its potential application in the dynamic surveillance of anti-HER2 therapies.
Ancestrally unbiased polygenic breast cancer (BC) risk assessment.
Authors: Hughes Elisha , Tiemeny Placede , Gallagher Shannon , Meek Stephanie , Eng Charis , Gary Monique , Gordon Ora , Klemp Jennifer R. , Olopade Olufunmilayo I. , Pederson Holly Jane , Weitzel Jeffrey N. , Whitworth Pat W. , Yehia Lamis , Wagner Susanne , Slavin Thomas Paul , Gutin Alexander , Lanchbury Jerry
Published: June 2021

10502

Background: BC risk is influenced by single-nucleotide polymorphisms (SNPs) with small effects that can be aggregated into polygenic risk scores (PRSs). PRSs have primarily been developed and validated for populations of European descent. To make a PRS available for all women, we developed and validated a novel global PRS (gPRS) that utilizes individual ancestral genetic composition. Methods: Ancestry-specific PRSs corresponding to 3 continental ancestries were developed from 149 SNPs (93 BC and 56 ancestry-informative): an African PRS was developed using a cohort of 31,126 self-reported African American patients referred for hereditary cancer testing; an East Asian PRS was developed based on published data from the Asia Breast Cancer Consortium; and a European PRS was developed using data from the Breast Cancer Association Consortium and 24,259 European hereditary cancer testing patients. For each patient, ancestry-informative SNPs were used to calculate the fractional ancestry attributable to each of the 3 continents. The gPRS was the sum of ancestry specific PRSs weighted according to genetic ancestral composition. In an independent validation cohort (N = 62,707), we evaluated discrimination and calibration of gPRS, and compared performance against a previously described 86-SNP PRS for women of European ancestry. Associations of SNPs and PRSs with BC were analyzed using logistic regression adjusted for personal and family cancer history, age, and ancestry. Odds ratios (ORs) are reported per standard deviation within the corresponding patient population. P-values are reported as two-sided. Results: The gPRS was strongly associated with BC in the full validation cohort and in sub-cohorts defined by self-reported ancestry (Table). 95% (88/93) of BC SNPs had ≥1% frequency of risk alleles within each of the self-reported populations. Compared to the aforementioned 86-SNP PRS, the gPRS showed improved discrimination overall, and within each sub-cohort, with the exception of the Asian population where the sample size was too small to show superiority of either score. The 86-SNP PRS was calibrated for white non-Hispanic women but mis-calibrated for non-European ancestries. The gPRS was properly calibrated for all women. Conclusions: The 149-SNP gPRS is validated and calibrated for women of all ancestries. Combined with clinical and biological risk factors, this approach may offer improved risk stratification for all women, regardless of ancestry.[Table: see text]
Underdiagnosis of germline genetic prostate cancer: Are genetic testing guidelines an aid or an impediment?
Authors: Esplin Edward D. , Cahn David J , Mazzarella Brian , Pieczonka Christopher Michael , Gazi Mukaram , Belkoff Laurence H. , Heron Sean , Modh Rishi , Berger Aaron D. , Morris David , Jayram Gautam , Idom Charles , Veys Joseph , Engelman Alexander , Bevan-Thomas Richard , Hardwick Mary Kay , Hatchell Kathryn E. , Nielsen Sarah M. , Nussbaum Robert Luke , Shore Neal D.
Published: June 2021

10504

Background: Pathogenic/likely pathogenic (P/LP) germline genetic variants are estimated to occur in 10-15% of all prostate cancer (PCa) patients. However, genetic testing for PCa patients is underutilized, partially due to complicated and restrictive testing guidelines developed at a time when the cost of testing was high. We conducted a study based in community urology clinics to determine the incidence of P/LP variants in PCa patients who met and did not meet the NCCN 2019 PCa germline genetic testing criteria. Methods: An IRB-approved, multicenter, prospective registry was initiated with 15 community and academic urologists nationwide. Eligibility criteria included patients with a PCa diagnosis unselected for personal or family history, stage or histology who had not been previously tested. Consecutive patients ages 18-90 were consented and underwent an 84-gene germline panel test. HIPAA-compliant electronic case report forms distributed to clinician collected information on patient diagnoses, NCCN testing criteria, and results-based recommendations. Results: To date, 640 enrolled patients have genetic testing results available. Overall, 69 (10.8%) patients had 72 P/LP variants detected, 15% of which were in BRCA1/2. Of the 532 patients for whom we have clinician-reported data, 293 (55%) met NCCN criteria and 239 (45%) did not. Median age was 70 (range 44-90). Overall, 11.1% (59/532) of patients with clinician-reported data had a P/LP variant. 36 (12.3%) of patients who met NCCN criteria and 23 (9.6%) of patients who did not meet criteria had a P/LP variant. The difference in P/LP rate between the two groups was not statistically significant (p=0.33). If only a conservative 12-gene PCa panel was considered, P/LP yield was 5.5% (29/532), with 8 (28%) of these patients missed by guidelines. Stratification by self-reported ethnicity was: 76% White/Caucasian (52 patients w/ P/LP), 18% Black/African American (2 patients w/ P/LP), and <5% each of Hispanic or Asian. Conclusions: There was no statistically significant difference in the yield of P/LP variants between patients who met and those who did not meet NCCN PCa guidelines, reinforcing that a significant number of P/LP variants are missed if NCCN guidelines are required for genetic testing. Expanded panel testing yields more medically actionable P/LP variants than testing BRCA1/2 alone or PCa panels with 12 genes. While 18% of the cohort was Black/African American, there was a lower P/LP rate (2%) relative to other groups, indicating that more research is needed to understand genetic variation in underrepresented populations with PCa.
Trends in cancer screening volumes at an urban health center during the COVID-19 pandemic.
Authors: Khan Mahir , Wright Margaret , Watson Karriem , Jain Shikha
Published: June 2021

10551

Background: The Coronavirus-19 (COVID-19) pandemic has disrupted cancer screening for reasons including healthcare resource preservation, infection control efforts, and patient factors. There is limited literature quantifying this interruption of care, particularly in vulnerable and racial/ethnic minorities. Methods: We compared the volume of cancer screening at the University of Illinois Hospital & Health Sciences System before and during the COVID-19 pandemic using data obtained from the electronic medical record. Modalities included mammogram, ultrasound, and MRI for breast; Pap test for cervical; colonoscopy, CT colonography, and flexible sigmoidoscopy for colorectal; low-dose CT for lung; and prostate-specific antigen test for prostate. Of note, screening and diagnostic tests could not be distinguished for colorectal cancer. We examined percent changes in cancer screening counts for each month from February 2020-August 2020, using January 2020 as a reference. Results were stratified by gender, race, and ethnicity. Results: Screening volume declined rapidly after January 2020, with the nadir for each cancer site occurring in April 2020: breast ( n = 0, -100%), cervical ( n = 169, -84%), colorectal ( n = 35, -89%), lung ( n = 0, -100%), and prostate ( n = 108, -72%). Values recovered by August 2020 for most cancer sites except cervical cancer, which remained decreased (-23%). There were no differences in screening trends by gender. With respect to race, breast screening volume in Black patients decreased earlier and exhibited slower recovery compared to White patients. White patients had poorer cervical screening recovery than Black patients by August 2020 (-60% vs. -23%). Hispanics had poorer recovery of breast screening compared to non-Hispanics by August 2020 (-23% vs. 6%). Conclusions: We observed widely decreased cancer screening attributable to COVID-19. Breast cancer screening data specifically showed persistent disparities affecting Black and Hispanic patients. Despite the reassuring recovery of multiple screening methods by August 2020, an increase above baseline is needed to compensate for initial declines. Further studies will likely reveal long-term consequences of this unprecedented situation.[Table: see text]
Adverse consequences of the COVID-19 pandemic on breast cancer stage distribution and breast cancer disparities.
Authors: Fasano Genevieve A. , Chen Yalei , Bayard Solange , Davis Melissa , Bea Vivian , Drotman Michele B. , Kagan Arleo Elizabeth , Marti Jennifer , Malik Manmeet , Simmons Rache M. , Swistel Alexander J. , Tamimi Rulla , Newman Lisa A.
Published: June 2021

10555

Background: The COVID-19 surge in March 2020 resulted in a hiatus placed on screening mammography programs in support of shelter-in-place mandates and diversion of medical resources to pandemic management. The COVID-related economic recession and ongoing social distancing policies continued to influence screening practices after the hiatus was lifted. We evaluated the effect of the hiatus on breast cancer stage distribution on the diverse patient population of a health care system in New York City, the first pandemic epicenter in the United States. Methods: Breast cancer patients diagnosed January 1, 2019 to December 31, 2020 were analyzed, with comparisons of stage distribution and mammography screen-detection for three intervals: Pre-Hiatus, During Hiatus (March 15, 2020 to June 15, 2020), and Post-Hiatus. Results were stratified by African American (AA), White American (WA), Asian (As) and Hispanic/Latina (Hisp) self-reported racial/ethnic identity. Results: A total of 894 patients were identified; of these, 549 WA, 100 AA, 104 As, and 93 Hisp comprised the final race/ethnicity-stratified study population. Overall, 588 patients were diagnosed Pre-Hiatus, 61 During-Hiatus, and 245 Post-Hiatus. Nearly two-thirds (65.5%) of the Pre-Hiatus cases were screen-detected versus 49.2% During-Hiatus and 54.7% Post-Hiatus (p = 0.002). Frequency of tumors diagnosed < 1 cm declined from 41.9% Pre-Hiatus to 31.7% Post-Hiatus (p = 0.035). WA patients were more likely to have screen-detected disease compared to AA in the Pre-Hiatus period (69.1% vs. 56.1%; p = 0.05) but non-significantly more likely to have screen-detected disease compared to As and Hisp patients (66.2% vs. 56.9%; p = 0.08). In the Post-Hiatus period, the frequency of screen-detected disease was highest among WA patients (63.0%) compared to all other racial/ethnic groups (AA; 48.1%, As-33.3%, and Hisp-40%; p = 0.007). Similar patterns were observed for frequency of tumors diagnosed ≤1cm Pre-Hiatus (WA-44.3% vs AA-26%, p = 0.02; and vs. As-41.3%, Hisp-48%; p = 0.09), and Post-Hiatus (WA-37.7% vs. AA-18.2%, As-30.8%, Hisp-23.5%; p = 0.25). Conclusions: The 3-month pandemic-related mammography screening hiatus resulted in a more advanced stage distribution for New York City breast cancer patients, and worsened pre-existing race/ethnicity-associated disparities, especially for AA pts.
Validation of a high performing blood test for multiple major cancer screenings.
Authors: Xu Linhao , Wang Jun , Ma Weifeng , Liu Xin , Li Sihui , Chen Siyu , Hu Qian , Yang Ting , Ye Zhujia , Chen Zhiwei , Fan Jianbing
Published: June 2021

10561

Background: Early detection at the localized stage is pivotal for the successful treatment of various cancer types. Although several cancers already have routine screening approaches, the comprehensive utilities are impeded for various reasons, e.g., low accuracy, high cost, limited availability of required facilities, especially in the developing countries. Therefore, an accurate, cost-effective, and non-invasive test for multiple major cancer screening is in high demand. We previously reported a cfDNA methylation test, which can detect five major cancer types with high specificity and sensitivity, especially at the early stage (stage I). These five major cancers, including lung cancer (LC), breast cancer (BC), colorectal cancer (CRC), gastric cancer (GC), and esophageal cancer (EC), account for 56% of new cancer cases and 60% of cancer-related deaths yearly in China. Here, we report the result in an independent cohort as a further validation of this multi-cancer screening test. Methods: The high-throughput targeted methylation profiling platform, Aurora, was used to analyze the plasma samples from an independent retrospective cohort containing 505 healthy controls and ̃200 cases for each cancer type. A locked model based on our previous pilot study (reported in AACR 2020 and 2021) was applied to this data set to assess the overall performance. Results: The Area Under Curves (AUC) of the classifier for LC, BC, CRC, GC and EC are 97.3%, 96.2%, 92.0%, 94.0% and 93.5%, respectively. At a fixed specificity of 99%, the sensitivities for LC, BC, CRC, GC and EC are 84%, 75%, 82%, 85% and 78%, respectively. Conclusions: A methylation blood test for five major cancer screening has been validated in a large retrospective cohort. Its high sensitivity for each cancer type, especially at the early stage (stage I), and easy to use suggests it can be implemented in real clinical world. A large prospective clinical trial is undergoing to further validate this test in asymptomatic populations.
Prior tonsillectomy and subsequent risk of breast cancer in females: Systematic review and meta-analysis.
Authors: Kacimi Salah Eddine Oussama , Ould Setti Mounir , Benmelouka Amira Yasmine , Aloulou Mohammad , Sekkal Hanane Zoubida , Shamseldin Laila Salah , Vidovic Jovana , Klouche-Djedid Selma Nihel , Shah Jaffer , Yasmin Farah , Riffi Omar , Afifi Ahmed M , Ghozy Sherief
Published: June 2021

10568

Background: Exposure to recurrent infections in childhood was linked to an increased risk of cancer in adulthood. There is also evidence that a history of tonsillectomy, a procedure often performed in children with recurrent infections, is linked to an increased risk of leukemia, and Hodgkin lymphoma. Tonsillectomy could be directly associated with cancer risk or it could be a proxy for another risk factor such as recurrent infections and chronic inflammation. Nevertheless, the role of recurrent childhood infections and tonsillectomy on the one hand, and the risk of breast cancer (BC) in adulthood remain understudied. Our study aims to verify whether a history of tonsillectomy increases the risk of BC in women. Methods: A systematic review was conducted using PubMed, Google Scholar, Scopus, Embase and Web of Science databases from inception through November 2020 to identify the studies which explored the association between history of tonsillectomy and BC in females. The Newcastle Ottawa Scale was used to assess the quality of included studies. Odds ratio (OR) was used to measure effect size. The Random/Fixed effects model was applied to synthesize the associations between tonsillectomy and BC risk based on heterogeneity. Heterogeneity was assessed using the I-squared statistic. A forest plot was generated, and publication bias was assessed. The leave-one-out sensitivity analysis was performed to check if results were driven by a single study. Results: Seven studies with a total of 7259 patients were included in our analysis; out of them, 2200 patients were diagnosed with BC. Patients with a history of tonsillectomy (n = 2843) showed higher subsequent risk of developing BC (OR = 1.252; 95% CI = 1.115 - 1.406; P < 0.001; I2 = 9%) as compared to patients without a history of tonsillectomy (n = 4416). Using the leave-one-out sensitivity analysis to iteratively remove one study at a time, we confirmed that no single study had a substantial influence on the overall effect size. Conclusions: Our study supports and confirms the evidence that a history of tonsillectomy is associated with an increased risk of breast cancer. These findings are also an argument in support of the hypothesis that recurrent childhood infections are linked with adulthood breast cancer.
Identification of potential germline (GL) variants by routine clinical comprehensive genomic profiling (CGP) and confirmatory GL testing in 24 tumor types.
Authors: Hanson Kristen , Mullane Michael , Schnettler Erica , Pavlick Dean C. , Frampton Garrett M. , Cooper Maureen , Wham Deborah , Thompson Michael A. , Godden Jennifer , Walters Mary , Venstrom Jeffrey Michael , McGregor Kimberly
Published: June 2021

10596

Background: Tumor CGP may identify both somatic and GL variants, though confirmatory testing is required to verify which variants originate from the GL. Studies have shown CGP can identify patients who both do and do not meet criteria for genetic counseling (GC). Ideally, improved annotation from tumor CGP could more appropriately direct GC referrals. We explore how a computational algorithm might be used to influence GC and confirmatory GL testing for variants in inherited cancer predisposition genes. Methods: 849 patients from the Aurora Oncology Precision Medicine Program who had routine hybrid-capture based CGP by Foundation Medicine from 8/2018-8/2020 were eligible. A previously published algorithm, SGZ (Sun et al PMID 29415044) which incorporates allele frequency, aneuploidy, and admixed copy number modeling was used to predict whether each single nucleotide variant (SNV) was GL or somatic. SGZ predictions for SNVs in 24 actionable inherited cancer predisposition genes were available to Aurora for review as part of standard screening to identify appropriate GC referrals. For patients who had GL testing, variants in genes on both assays were compared. Results: 76 pathogenic (P) or likely pathogenic (LP) variants predicted to be GL by SGZ were detected in 73/849 (9%) patients: ATM (7), BAP1 (2), BRCA1 (13), BRCA2 (8), BRIP1 (1), CHEK2 (18), FH (0), FLCN (2), MLH1 (1), MSH2 (0), MSH6 (3), MUTYH (12), PALB2 (3), PMS2 (1), POLE (0), RAD51C (1), RAD51D (0), RET (1), SDHA/B/C/D (0,0,0,0), TSC2 (0), and VHL (3). 27/73 (37%) patients had GL testing. 25/26 (96%) variants were confirmed to be GL in origin and 1 additional variant was detected by CGP in a region not interrogated by the GL assay: ATM (2/2), BRCA1 (6/6), BRCA2 (2/2), BRIP1 (1/1), CHEK2 (9/9), FLCN (0*/1), MSH6 (1/1), MUTYH (2/2), PALB2 (1/1), RAD51C (1/1), and VHL (0/1). Variants were confirmed in bladder, breast, CRC, glioma, NSCLC, ovary, pancreas, prostate, sarcoma, and gastric cancer. The VHL variant was discordant in a leiomyosarcoma. Conclusions: We identified the potential real-world clinical impact of computationally screening solid tumor patients undergoing routine CGP for potential P/LP GL variants. Predicting GL results with SGZ for 24 inherited cancer predisposition genes was highly concordant with confirmatory GL testing independent of tumor type. CGP annotations can facilitate GC referral and GL testing for at-risk patients, particularly in tumor types which may not typically meet guidelines for GL testing.[Table: see text]
Romidepsin (HDACi) plus cisplatin and nivolumab triplet combination in patients with metastatic triple negative breast cancer (mTNBC).
Authors: Sharma Priyanka , Abramson Vandana G , O'Dea Anne , Nye Lauren Elizabeth , Mayer Ingrid A. , Crane Gregory James , Elia Manana , Yoder Rachel , Staley Joshua M , Schwensen Kelsey , Finke Karissa , Heldstab Jaimie , LaFaver Stephanie , Prager Micki , Williamson Stephen K. , Phadnis Milind , Reed Gregory A , Kimler Bruce F. , Khan Qamar J. , Godwin Andrew K.
Published: June 2021

1076

Background: Histone deacetylase inhibitors (HDACi) upregulate genes involved in antigen presentation machinery and increase expression of natural killer group 2, member D ligands (NKG2DL), thus resulting in enhanced tumor cell recognition and response to PD-1/CTLA-4 blockade. Cisplatin and HDACi combination synergistically induces cytotoxicity, apoptosis, and DNA damage. This phase I-II trial investigated combination of romidepsin (HDACi) plus cisplatin and nivolumab (PD-1 inhibitor) in mTNBC. Patients and Methods: Eligible patients had mTNBC with any number of prior chemotherapies. Phase I was 3+3 dose-escalation design with three dose levels of romidepsin (8, 10, 12mg/m2, D2, 9) plus cisplatin 75mg/m2 D 1 every 21 days. Phase II treatment included romidepsin plus cisplatin plus nivolumab 360mg every 21 days and was designed according to Simon’s two stage minimax design. Primary endpoints were recommended phase 2 dose (RP2D) and objective response rate (ORR). Additional endpoints included safety, PFS, and pharmacokinetics. Results: 51 patients were enrolled (N=13 phase I, N=38 phase II) between 2015-2020. 69% had received ≥1 prior metastatic chemotherapy, 47% had prior platinum, 53% had liver metastasis, 12% had BRCA1/2 mutation, and 11% had PD-L1 positive disease. There were no dose limiting toxicities in phase I. The RP2D was romidepsin 12mg/m2 D2,9 + cisplatin 75mg/m2 D1 + nivolumab 360mg D1 every 21 days. Thrombocytopenia (G3:27%, G4:0%), neutropenia (G3:25%, G4:0%), anemia (G3:22%, G4:0%), nausea (G3:22%, G4:0%), and vomiting (G3:20%, G4:0%) were the most common grade 3/4 adverse events. 21% of patients had immune AEs (G3-4:8%). Among 34 evaluable phase II patients, ORR was 44% (Table), median PFS was 4.4 months, and 1-year PFS was 23%. Median OS was 10.3 months and 1-year OS was 43%. No pharmacokinetic interactions were detected with co-administration of romidepsin-cisplatin-nivolumab. Conclusions: The triplet combination of romidepsin plus cisplatin and nivolumab was well tolerated and shows encouraging efficacy in pretreated mTNBC, including in patients with PD-L1 negative disease and in those with liver metastasis. Correlative biomarker work is ongoing. This combination warrants further evaluation in larger studies. Clinical trial information: NCT02393794 .[Table: see text]
A phase 2 study of pamiparib in the treatment of patients with locally advanced or metastatic HER2-negative breast cancer with germline BRCA mutation.
Authors: Sun Tao , Shi Yanxia , Cui Jiuwei , Yin Yongmei , Ouyang Quchang , Liu Qiang , Zhang Qingyuan , Chen Yiding , Zhimin Shao , Wang Shouman , Wang Xiaojia , Tong Zhongsheng , Zhong Yahua , Yan Min , Yan Xi , Wang Chuan , Yang Haiyuan , Li Miao , Xiang Xiao , Xu Binghe
Published: June 2021

1087

Background: Breast cancer is the most common cancer among women, with up to 37% of patients (pts) harboring germline BRCA1/2 mutations (g BRCA1/2m) that appear to be sensitive to poly (ADP-ribose) polymerase proteins 1 and 2 (PARP1/2) inhibition. Pamiparib is an orally administered selective PARP1/2 inhibitor that has the potential to cross the blood-brain barrier. This study evaluated the efficacy and safety of pamiparib in pts with locally advanced/metastatic human epidermal growth factor receptor 2-negative (HER2-) breast cancer, with deleterious or suspected deleterious g BRCA1/2m, who received ≤ 2 prior lines of chemotherapy. Methods: In this open-label, phase 2, multi-center study in China (NCT03575065), pts with locally advanced/metastatic HER2- breast cancer with deleterious or suspected deleterious g BRCA1/2m triple negative breast cancer (TNBC cohort) or hormone receptor-positive (HR+)/HER2- breast cancer (HR+ cohort) were enrolled. Pts received pamiparib 60 mg orally twice daily in 28-day cycles. The primary endpoint was objective response rate (ORR; RECIST v1.1) by independent review committee (IRC). Secondary endpoints included duration of response (DOR) and progression free survival (PFS) by IRC, overall survival (OS), safety and tolerability. Results: 88 pts were enrolled (median age 45.5 years), 76 pts (TNBC cohort n = 55; HR+ cohort n = 21) had measurable disease at baseline per IRC. 60 pts (68.2%) received 1 or 2 prior lines of chemotherapy; 42 pts (47.7%) were treated with platinum previously. Median follow-up was 13.77 months (TNBC cohort, 10.87 months; HR+ cohort, 18.45 months). In the TNBC cohort: confirmed ORR was 38.2% (95% CI: 25.4–52.3); median DOR (mDOR) was 6.97 months (95% CI: 3.94–not estimable[NE]); median PFS (mPFS) was 5.49 months (95% CI: 3.65–7.33); median OS (mOS) was 17.08 months (95% CI:13.70–NE). In the HR+ cohort: confirmed ORR was 61.9% (95% CI: 38.4–81.9); mDOR was 7.49 months (95% CI: 5.55–14.75); mPFS was 9.20 months (95% CI: 7.39–11.93); mOS was not reached (NR; 95% CI 18.10–NE). ≥ Grade 3 treatment emergent adverse events (TEAEs) occurred in 54 pts (61.4%); anemia was the most common TEAE, occurring in 77 pts (87.5%). Dose reduction due to TEAEs occurred for 57 pts (64.8%); discontinuations due to TEAEs occurred for 2 pts (2.3%). Conclusions: Pamiparib showed a promising response in pts with locally advanced/metastatic HER2- breast cancer with a g BRCA1/2m. The safety profile of pamiparib was considered acceptable and was generally consistent with therapies in the same class. Clinical trial information: NCT03575065 .[Table: see text]
Clinical outcomes in patients (pts) with a history of central nervous system (CNS) metastases receiving talazoparib (TALA) or physician’s choice of chemotherapy (PCT) in the phase 3 EMBRACA trial.
Authors: Litton Jennifer Keating , Ettl Johannes , Hurvitz Sara A. , Martin Miguel , Roche Henri , Lee Kyung-Hun , Goodwin Annabel , Usari Tiziana , Lanzalone Silvana , Guenzel Carolin , Blum Joanne Lorraine , Rugo Hope S.
Published: June 2021

1090

Background: In the EMBRACA trial (NCT01945775) of pts with germline BRCA1/2-mutated HER2-negative locally advanced/metastatic breast cancer (ABC), the poly(ADP-ribose) polymerase (PARP) inhibitor TALA significantly improved progression-free survival (PFS) vs PCT (8.6 vs 5.6 mo; HR [95% CI] 0.54 [0.41-0.71]; P < 0.0001). Patient-reported outcomes favored TALA, and most common adverse events included anemia, fatigue, and nausea. Previous subgroup analyses found that pts with a history of CNS metastases had improved PFS for TALA vs PCT (HR [95% CI] 0.32 [0.15-0.68]; P = 0.0016) and improved objective response rate (ORR) 63.2% vs 15.8%, respectively (odds ratio [95% CI] 8.95 [1.86-52.26]; P = 0.0013). This retrospective subgroup analysis further explored the clinical characteristics and outcomes in pts with a history of CNS metastases in EMBRACA. Methods: Pts were randomized 2:1 to TALA or PCT. Pts with adequately treated and stable CNS metastases not requiring corticosteroids were included. This analysis assessed intracranial ORR and best overall response (BOR) based on investigator assessment per RECIST 1.1 in pts with intracranial disease at baseline (data cutoff 15-Sep-17), and overall survival (OS; data cutoff 30-Sep-19). Results: In the intent-to-treat (ITT) population, 63 pts (43/287 [15.0%] TALA and 20/144 [13.9%] PCT) had a history of CNS metastases, of which 33 (11.5%) pts (TALA) and 15 (10.4%) pts (PCT) had intracranial disease at baseline. Additional baseline characteristics are shown in the table. Intracranial ORR in pts with intracranial disease at baseline and unconfirmed complete or partial response was 18.2% (TALA) vs 20.0% (PCT) (odds ratio [95% CI] 0.78 [0.13-5.80]; P = 0.765). In pts with intracranial disease at baseline, an intracranial BOR of stable disease was 69.7% for TALA vs 33.3% for PCT. Median OS in pts with a history of CNS metastases was 12.9 mo (95% CI 9.4-15.6) for TALA and 13.4 mo (95% CI 8.8-17.6) for PCT (HR [95% CI] 0.67 [0.37-1.2]; P = 0.1936 [stratified log-rank test]). In the safety population ([n = 43, TALA]; [n = 19, PCT]), median treatment duration (range) with TALA was 5.0 (0.1-36.0) mo compared with 2.1 (0.4-6.9) mo for PCT. Conclusions: In this subgroup analysis, baseline characteristics between pts with a history of CNS metastases treated with TALA or PCT were comparable. More pts with intracranial disease at baseline treated with TALA vs PCT experienced stable disease. Intracranial ORR in pts with intracranial disease was 18.2% for TALA vs 20.0% for PCT. Treatment options for pts with a history of CNS metastases are limited and further investigation in larger data sets is warranted. Clinical trial information: NCT01945775 .[Table: see text]
Systemic chemotherapy in patients with brain only metastatic breast cancer: A retrospective analysis.
Authors: Puri Akshjot , Mylavarapu Charisma , Ensor Joe E. , Parveen Parveen , Tremont-Lukats Ivo , Chang Jenny Chee Ning , Niravath Polly Ann
Published: June 2021

1093

Background: The treatment of patients with brain only metastatic breast cancer (BO-MBC) remains very challenging. There is also very limited literature informing on appropriate treatment or natural history of this entity. Systemic chemotherapy in addition to targeted therapy and/or anti-estrogen treatment is often used, but little is known if it adds to the overall or disease free survival. In this retrospective study, we examine this, as well as other factors which may be associated with increased risk of CNS or systemic recurrence in these patients. Methods: A database search at a single institution identified 178 patients with brain metastases (BM) from breast cancer out of which 45 patients had BO-MBC between 2007-2020. We collected demographic, clinical, radiographic and other treatment data. Leptomeningeal disease (LMD) was diagnosed by cerebrospinal fluid (CSF) cytology, neuroimaging, or both. We used the Brookmeyer and Crowley method. Results: The patients were followed for a median of 17.9 months; 36 out of 45 patients (80%) received local treatment for BM (surgery/radiation/both) and HER2 directed antibodies or tyrosine kinase inhibitors and/or anti-estrogen treatment, whereas 9 out of 45 patients (20%) received systemic chemotherapy in addition. There were 22 out of 45 (49%) HER2 +, 5 out of 45 (11%) HR + and 18 out of 45 (40%) triple negative breast cancer (TNBC) patients. There were 17 out of 45 patients (38%) who were deemed to have low burden of BM (defined as one to three BM and largest being ≤3 cm) whereas there were 24 out of 45 patients (53%) who had high burden of BM (defined as four or more BM or largest being > 3 cm). Conclusions: Patients with BO-MBC represent a distinct entity. Despite having better survival than patients with BM and extra CNS disease these patients have a high risk of developing LMD, CNS and systemic recurrences. The addition of chemotherapy to targeted therapy and/or anti-estrogens does not decrease the rates of systemic or CNS recurrence. The ER+ subset have a lower rate of development of systemic disease, as expected due to their relatively indolent biology. The CNS and systemic recurrence seem to be higher in patients with HER2+ cancers and counterintuitively even in those with low burden of BM; albeit these were statistically insignificant.[Table: see text]
Digital footprint of hematology-oncology fellowship programs: Identifying gaps after the first virtual recruitment season.
Authors: Velazquez Manana Ana I. , Abuali Inas , Rodriguez Vargas Juan J. , Aslanova Minira , Molina Aponte Yaniris , Romero Ramos Yaideliz , Duma Narjust
Published: June 2021

11003

Background: The COVID-19 pandemic has led to unprecedented restrictions to travel and in-person activities that limit hematology/oncology (HO) fellowship programs’ (FP) recruitment activities. Prospective applicants rely on websites and social media (SOME) to guide their decisions of applying or ranking a FP. We aim to evaluate HO FP’s digital footprint in order to identify informational gaps. Methods: The AMA Fellowship and Residency Electronic Interactive Database (FREIDA) was queried for all HO programs. We searched Google, Twitter, Instagram, Facebook, and YouTube for HO FP pages. Content was evaluated using published criteria. Qualitative content analysis of SOME posts is planned. Results: Our analysis includes 176 FP that actively recruited during the 2020 match season. Over half (57%, n = 100) were university-based and the median number of fellow positions per year was 4 per FP (range 0-16). Most FP had websites (95%, n = 167) with varying information (Table) for prospective applicants. Twenty percent (n = 33) included a diversity statement. While 63% (n = 106) of FP provided application information, only 51% discussed visa requirements. Few FP websites included key information such as why fellows chose a particular FP (7%, n = 12), accolades of fellows (3%, n = 5), or employment location of alumni (25%, n = 44). Only 42% (n = 69) provided city, and 5% (n = 8) showed fellows socializing. Thirty-four FP (19%) have informational videos (range 1-10) in YouTube (length range: 1:37-18:15min). Most (82%; n = 28) were published since May 2020 in alignment with the FP recruitment season. Twitter was the second most common SOME platform, used by 19% (n = 32) of FP. 56% (n = 18) joined Twitter since May 2020 correlating with the current recruitment season. The number of Twitter followers (median 119, range: 0-1408) and posts (median 47, range: 0-687) varied across FP. Only 4% used Facebook and 6% Instagram. Conclusions: Our analysis of FP’s digital footprint revealed that applicants participating in the 1st virtual HO recruitment season were provided limited online information. Programs can use online content to provide information on resources, research opportunities, and achievements of faculty and fellows that can guide applicant decision making. In the era of COVID-19, highlighting the diversity and breath of each FP, hospital, and city are vital to attract a diverse and talented pool of trainees.[Table: see text]
Minding the gap: Gynecologic oncology practices differ by gender.
Authors: Temkin Sarah Madhu , Chapman Eloise , Kohn Elise C. , Nair Navya , Blank Stephanie V.
Published: June 2021

11011

Background: Although most gynecologic oncologists (GOs) are now women, gender differences in clinical practice and compensation persist. Practice characteristics and infrastructural support that may influence gender-based differences were explored. Methods: Every 5 years, the Society of Gynecologic Oncology (SGO) conducts a member survey that provides details on member demographics, practice characteristics, activities, and revenue. Between 8/15-9/30/19 SGO members received a direct link to the survey. Gender was self-identified. Differences in responses were evaluated by gender. Results: Of 1425 surveys delivered, 690 were completed (48% response rate). 312 (45%) identified as male; 367 (53%) as female; 1 nonbinary; 1 other; 7 no response. Male GOs were more likely white (75 vs 68%, p=0.048), married (91 vs 81%, p<0.001), heterosexual (94 vs 90%, p=0.045), and hold an academic rank of professor (23 vs 12%, p<0.001). Practice setting and number of partners were similar. Chemotherapy prescribing was more common for females (82 vs 73%, p=0.004), but other clinical activities were similar (Table). Female GOs had lower clinical volumes than males for cervical, ovarian, vaginal/vulvar cancer and benign gynecologic procedures. Females reported fewer medical assistants and transcriptionists supporting their clinical activities. Overall and practice support was higher for male GOs although hospital support was similar for both genders. Female GOs reported more time spent on research (26 vs 19%, p=0.005), but the same research support. Conclusions: Clinical activities, specifically chemotherapy prescribing, and support differ for male and female GOs and may explain gender inequities. Clinical support should be equalized to maximize workplace productivity regardless of gender. Coordination of support between the practice and hospital and standard compensation for chemotherapy prescribing could decrease the large gender wage gap in this specialty.[Table: see text]
Supporting the mental well-being of healthcare professionals during a pandemic.
Authors: Lopez Ana Maria , Capparella Lisa , Pomerantz Miriam , Naputo Kristine , Leader Amy , O'Hayer C. Virginia Virginia
Published: June 2021

11037

Background: Burnout amongst healthcare professionals has been well-documented as a phenomenon that compromises the quality and viability of patient-centered care, particularly in oncology. Due to the extraordinary demands of the pandemic, burnout has emerged as a public health crisis that warrants immediate attention to preserve the wellbeing of healthcare staff. At the onset of the pandemic, The Sidney Kimmel Cancer Center (SKCC) at Jefferson, an urban NCI-designated cancer center, translated its support offerings to virtual events. Initially, healthcare providers (HP) sought support by attending patient programs. In response, SKCC initiated virtual programming to support the well-being and needs of the HP team. Methods: Within weeks of the state shutdown due to the pandemic, programs were initiated to address HP self-reported distress: Coping Effectively and Mindfulness Moments Each 30-minute session was facilitated by a licensed psychologist and social worker. Coping Effectively offers strategies from evidence based treatment including Dialectical Behavior Therapy, Acceptance and Commitment Therapy, and Cognitive Behavioral Therapy, to cope with distress and burnout. Mindful Moments draws from Mindfulness Based Stress Reduction practices including observing breath and guided meditations. These programs have been offered consistently throughout the pandemic. Schwartz Rounds, geared towards supporting the human side of healthcare, provided “hot” topic moderated discussions, four of which focused on the pandemic These discussions allow for HP to come together to discuss difficult topics and emotions impacting a variety of professionals. All programming was evaluated with a single question to measure the impact of the session on reducing distress. Each program began and ended with a poll asking, “How distressed do you currently feel?” Attendees respond on a Likert scale from 0 to 10, in which10 indicated the highest level of distress. Results: Since March 31st, 340 staff have attended Mindful Moments and 236 staff have attended Coping Effectively. From March 2020-February 2021, 382 attendees measured their distress before and after attending a staff program. Schwartz Rounds hosted 471 HP from a variety of disciplines. Participants were asked to complete an evaluation following rounds. 31% of program participants’ completed an evaluation form and 89% rated the program exceptional/very good. Conclusions: Despite the challenges of COVID-19, the pivot to virtually create programs to support staff during the pandemic was swift and thoughtful. The increased attendance and the feedback from evaluations are promising indicators of decreasing burnout amongst HP. How Distressed do you Currently Feel? (Average Score scale 1-10)[Table: see text]
PD1 inhibition in soft-tissue sarcomas with tertiary lymphoid structures: A multicenter phase II trial.
Authors: Italiano Antoine , Bessede Alban , Bompas Emmanuelle , Piperno-Neumann Sophie , Chevreau Christine , Penel Nicolas , Bertucci Francois , Toulmonde Maud , Bellera Carine A. , Guegan Jean-Philippe , Sautes-Fridman Catherine , Bougoüin Antoine , Cantarel Coralie , Le Loarer Francois , Blay Jean-Yves , Fridman Wolf-Herman
Published: June 2021

11507

Background: PD1 inhibition has shown limited activity in all comers clinical trials including patients with advanced soft-tissue sarcomas (STS). In the PEMBROSARC study, objective response rate, progression-free (PFS) and overall survival (OS) were respectively 2.1%, 1.4 and 7.1 months respectively (Toulmonde et al. Jama Oncol 2017). We have recently shown that the presence of tertiary lymphoid structures (TLS) may represent a biomarker to select patients who are more likely to benefit from immunotherapy (PetitPrez et al., Nature 2020). We report here the first clinical trial investigating the efficacy of PD1 inhibition in TLS-positive STS. Methods: PEMBROSARC is an open-label multicenter phase II study of pembrolizumab in combination with low-dose cyclophosphamide in pts with STS selected based on the presence of TLS. TLS status has been assessed centrally has previously described (PetitPrez et al., Nature 2020). Eligible patients received pembrolizumab 200mg IV q21 days and cyclophosphamide 50 mg BID 1week on, 1 week off. All patients had confirmed progressive disease at inclusion based on central review of two imaging performed at less than 6 months interval. The primary efficacy endpoint was 6-month non-progression (as per RECIST evaluation criteria v1.1). Based on the following hypotheses: 15% 6-month non-progression rate (H0), 40% acceptable 6-month non-progression rate (H1), 5% type I error rate, 90% power, a total of 29 assessable patients were necessary and 8 patients or more had to be progression-free at 6 months to reach the first endpoint. Results: 240 patients were screened for TLS status between September 2018 and January 2020 in 7 centers of the French Sarcoma Group. Among them, 48 were found to be TLS+ as per central review and 35 were included in the study. The three most frequent histological subtypes were: well-differentiated/dedifferentiated liposarcoma (n = 13); UPS (n = 6), and leiomyosarcoma (n = 4). 30 patients were eligible for efficacy. Of those, as per central imaging review, 13 patients (43.3%) had tumor shrinkage resulting in partial response in 8 patients (26.7%) and stable disease in 5 cases (16.7%). 10 patients had progressive disease. Twelve patients were progression-free at 6 months (40.0% 95%CI = [22.7 – 59.4]).Median PFS and OS were 4.1 months (95%CI, 1.4-9.6) and 14.5 months (95%CI, 8.5- 18.3 months), respectively. Conclusions: With an objective response and a 6-month non-progression rates of 26.7% and 40% respectively versus 2.1% and 4.2% in all comers, the PEMBROSARC study confirms that selection based on TLS status is an efficient approach to tailor immunotherapy in STS patients. Clinical trial information: NCT02406781.
Phase (Ph) 1b/2 evaluation of olaratumab in combination with gemcitabine and docetaxel in advanced soft tissue sarcoma (STS).
Authors: Attia Steven , Villalobos Victor Manuel , Hindi Nadia , Van Tine Brian Andrew , Wagner Andrew J. , Chmielowski Bartosz , Levy Donna Elise , Ceccarelli Matteo , Jones Robin Lewis , Dickson Mark Andrew
Published: June 2021

11517

Background: Doxorubicin (doxo) remains standard first-line therapy for advanced STS. Doxo in combination with olaratumab (O) demonstrated superior clinical activity compared to doxo alone in a Ph 2 trial (NCT01185964), although this was not confirmed in the subsequent Ph 3 trial (NCT02451943). Gemcitabine (G) plus docetaxel (D) is a second line therapy for advanced STS. Here, we report a concurrent Ph 2 study that explored a second-line addition of O to G and D for advanced STS (ANNOUNCE 2 NCT02659020). Methods: Adult patients (pts) with unresectable locally advanced or metastatic STS, ≤ 2 prior lines of systemic therapy, and ECOG PS 0-1 were eligible. Pts were enrolled from 2 cohorts: O-naïve and O-pretreated. In both cohorts, pts were randomized 1:1 to either O, G plus D or placebo (PBO), G plus D. Pts received 21-day cycles of O (20 mg/ kg cycle 1 and 15 mg/kg other cycles, day (d) 1 and d8), G (900 mg/m2, d1 and d8) and D (75 mg/m2, d8). Pts continued treatment until progression, toxicity, or withdrawal. Randomization was stratified by histology (leiomyosarcoma [LMS] vs non-LMS), prior systemic therapy, ECOG PS, and prior pelvic radiation. The primary objective was overall survival (OS) in the O-naïve population using an alpha level of 0.20. Secondary endpoints included OS (O-pretreated) and other efficacy parameters, as well as safety and pharmacokinetics (PK). Results: 167 pts were enrolled in the O-naïve cohort and 89 pts in the O-pretreated cohort. Baseline patient characteristics were well balanced. OS for O-naïve pts was 16.8 vs 18.0 months (m) (hazard ratio [HR] = 0.95, 95% CI: 0.64-1.40; p = 0.78) for the investigational vs control arm, respectively. Other efficacy outcomes are presented in the table. Safety was manageable across treatment arms. PK parameter estimates for O were consistent with previous studies. Conclusions: There was no statistically significant difference in OS between the two arms in the O-naïve population. However, while not statistically significant, the combination of O, G and D demonstrated favorable OS in the O-pretreated cohort, and PFS and objective response rate (ORR) in both cohorts. For O-naïve pts, a clinically meaningful progression-free survival (PFS) improvement was observed. Further investigations in specific histological subtypes are ongoing. Clinical trial information: NCT02659020. [Table: see text]