bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and biological features prognostic of survival after relapse of INRGSS-stage MS pattern neuroblastoma: A report from the International Neuroblastoma Risk Group (INRG) project.
Authors: Campbell Kevin M. , Kao Pei-Chi , Naranjo Arlene , Kamijo Takehiko , Ramanujachar Ramya , London Wendy B. , DuBois Steven G. 
Published: June 2022

10044 Background: Neuroblastoma (NB) presenting with INRGSS MS metastatic pattern highlights the extreme heterogeneity within NB and subsequent difficulty in risk assignment. Depending on tumor biology, patients with stage MS disease may be classified as very-low risk or as high-risk. While outcomes at initial diagnosis have been well-described, outcomes after relapse are less well defined. Methods: From the INRG Data Commons, we investigated clinical and biological characteristics of patients diagnosed 1984-2021 with stage MS pattern NB (INSS stage 4s, INSS stage 4 or INRG stage MS) who subsequently experienced disease relapse or progression, excluding patients whose first event was death. Using Kaplan-Meier methods, post-relapse overall survival (OS)± standard error (SE) was calculated from the time of first relapse/progression until death or last contact, overall and by era of diagnosis: < 2000 vs ≥2001. Univariate Cox models were used to identify factors prognostic of post-relapse OS. Results: 209 patients met eligibility criteria,103 diagnosed < 2001 and 106 ≥2001. Of patients diagnosed ≥2001, 89% (n = 94) were < 365 days old at diagnosis; tumors were MYCN amplified in 21% (21/102) and diploid in 31% (20/64). Of this same cohort, time from initial diagnosis to relapse was < 6 months in 40% (n = 42), 6-12 months in 25% (n = 26), and > 12 months in 36% (n = 38) of patients. Of 60 patients with known site of relapse/progression diagnosed ≥2001, 73% (44) were metastatic (29) or primary plus metastatic (15). Among these, 16% (5/32) remained stage MS pattern while 84% (27/32) had metastatic sites beyond MS sites. Five-year post-relapse OS±SE was 53±3.5% overall (n = 209), and higher for those diagnosed ≥2001 (62±5.0%; n = 106) compared to those diagnosed < 2001 (44±4.9%; n = 103) (p = 0.0046). In patients diagnosed ≥2001, factors prognostic of superior post-relapse OS included: age < 365 days; not Hispanic; MYCN non-amplified; no 1p loss/aberration, hyperdiploidy; low/intermediate MKI; LDH < 1400 U/L, favorable INPC histology; and < 12 months from initial diagnosis to first relapse. Conclusions: Most patients with relapsed stage MS NB have metastatic relapse and these relapses more commonly occur at sites outside liver, skin, and bone marrow. Patients diagnosed ≥2001 with MS pattern NB have substantially better post-relapse OS compared to those diagnosed < 2001. In the cohort of patients with MS pattern NB diagnosed ≥2001, most of the well-accepted prognostic factors for OS at diagnosis are also prognostic of post-relapse OS.
Thyroid gland definitive ultrasound screening in childhood cancer survivors following radiotherapy.
Authors: Baran Julia A. , Halada Stephen , Bauer Andrew J. , Li Yimei , Isaza Amber , Patel Tasleema , Sisko Lindsay , Ginsberg Jill P. , Kazahaya Ken , Adzick N. Scott , Mostoufi-Moab Sogol 
Published: June 2022

10049 Background: Childhood cancer survivors (CCS) are at risk for radiotherapy (RT) late effects, including second malignancies. Optimal screening for thyroid cancer (TC) in CCS post-RT remains controversial. We assessed the clinical benefit of thyroid ultrasound (US) surveillance in CCS exposed to RT. Methods: 316 CCS (175 males) were prospectively surveilled with thyroid US between 2002 and 2021 at the Children’s Hospital of Philadelphia. Patients were screened upon referral to the Survivorship Program. Thyroid US, clinicopathologic features, and endocrine-related outcomes were ascertained. Outcomes were compared using primary CCS diagnosis age cohorts of ≤ 3, > 3 to ≤ 10, and > 10 years. Risk factors for thyroid nodule(s) and TC were evaluated using Kruskal Wallis and ANOVA [OR (95% CI)]. Results: The most common CCS diagnoses were leukemia (32%), CNS tumor (26%), and neuroblastoma (18%). Patients received TBI (43%) and/or RT to craniospinal (43%), chest (13%), and neck regions (7%). About 48% (n = 152) of patients presented thyroid nodule(s) (Table). Forty-six patients underwent surgery, and 28 had TC, including 19 with ATA low-risk, 2 with ATA intermediate-risk, and 7 with ATA high-risk disease. Of the 9 patients with intermediate- or high-risk disease, 5 were ≤ 3 years, 3 were > 3 to ≤ 10 years, and 1 was > 10 years at the time of RT exposure. Eight patients with TC demonstrated pathogenic variant(s). RT exposure at ≤ 3 years old conferred 2-fold increased risk for nodule(s) compared to RT at > 10 years [OR = 2.14 (1.44-2.84) p = 0.03]. Female sex [OR = 1.73 (1.25-2.21) p = 0.02] and greater interval between RT and first US [OR = 1.10 (1.04-1.15) p = 0.001] were additional independent risk factors. Conclusions: Younger age at RT exposure is associated with increased risk of and shorter latency for developing TC. Thyroid US surveillance appears most beneficial in CCS exposed to RT ≤ 3 years old in an effort to diagnose TC at an earlier stage prior to metastasis. [Table: see text]
Treatment exposure-based risk-stratification for care of survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.
Authors: Dinan Michaela Ann , Stratton Kayla , Leisenring Wendy M. , Yasui Yutaka , Chow Eric Jessen , Moskowitz Chaya S. , Yeh Jennifer M , Noyd David H , Armstrong Gregory T. , Oeffinger Kevin C. 
Published: June 2022

10056 Background: Treatment exposure-based risk-stratification oflong-term cancer survivors is needed to allocate tailored health care in survivorship clinics. Investigators from the United Kingdom (UK) developed a treatment exposure-based algorithm that stratifies survivors into low, medium, and high risk groups. Because this algorithm has not been validated, we sought to use the large, diverse population of the Childhood Cancer Survivor Study (CCSS) to validate risk for poor outcomes. Methods: Five-year survivors of childhood cancer (diagnosed between 1970-1999 at < 21 years of age) were categorized into low, medium, and high risk groups based on treatment exposures and diagnoses (Table). Primary endpoints included cumulative health-related (i.e., non-recurrence, non-external) late mortality and cumulative incidence of grade 3-5 chronic conditions (CTCAEv4.03) conditional on reaching age 20 without the outcome. Siblings were a comparison group for chronic conditions. Cox proportional hazards models among survivors estimated hazard ratios (HRs) and 95% confidence intervals (CI) adjusted for sex and race. Results: A total of 21,504 survivors were analyzed with a median follow-up of 22 years. Application of the risk stratification algorithm resulted in 3,152 low risk, 6,443 medium risk, and 11,909 high risk survivors. Among those who survived to age 20 without any grade 3-5 conditions, the risk of developing one by age 35 was 12.2% (95% CI 1.0-14.7%), 14.2% (12.8-15.7%) and 25.4% (24.2-26.6%) for low, medium, and high-risk patients, respectively, and 6.9% (6.1-7.9%) for siblings. HRs of grade 3-5 conditions for medium (HR 1.8, 95% CI 1.6-2.1) and high (HR 3.9, 95% CI 3.5-4.4) risk relative to low risk survivors, respectively, were elevated. Cumulative health-related mortality was similarly associated with risk categories; conditional on being alive at age 20, survivors within low, medium, and high risk groups had cumulative incidences of 2.3% (95% CI 1.7-3.1%), 3.3% (2.8-3.9%) and 6.1% (5.6-6.6%), respectively, by age 35. Conclusions: Risk categorizations based on treatment exposures were effective at providing generalized risk stratification within the CCSS with respect to risk of grade 3-5 conditions and health related mortality, particularly for identifying high risk survivors. These risk groups may be useful to physicians in determining follow-up intervals and guiding management and long-term surveillance of these survivors. [Table: see text]
Effect of socioeconomic status as measured by Neighborhood Deprivation Index on survival in metastatic breast cancer.
Authors: Puthanmadhom Narayanan Susrutha , Rosenzweig Margaret Q. , Ren Dianxu , Oesterreich Steffi , Lee Adrian V. , Brufsky Adam 
Published: June 2022

1013 Background: Socioeconomic status (SES) and race are major determinants of health outcomes in the United States. We aim to assess the effect of SES as measured by the Neighborhood Deprivation Index (NDI) and race on outcomes in metastatic breast cancer patients at our center. Methods: The NDI scores for patients with metastatic breast cancer who were treated at our center between 2000 and 2017 were obtained from the Neighborhood Atlas using their Zip-Code (N = 1246). The SES groups were defined as low deprivation with an NDI score in the bottom tertile and high deprivation with NDI in the top or middle tertiles. Baseline characteristics were compared between the SES groups with Bonferroni correction. Univariate and multivariate survival analysis were performed using the R packages “survival” and “survminer”. Results: Race was the only baseline characteristic that was significantly different between the SES groups, the high deprivation group had a higher proportion of African Americans (10.5%) than the low deprivation group (3.7%, P = 9.3e-05). In univariate Kaplan-Meier survival analysis, both SES and race had significant effect on overall survival such that the high deprivation group had worse survival than low deprivation (Log Rank P = 0.01) and African Americans had worse survival than Caucasians (P = 0.008). In multivariate Cox proportional hazard model, SES, but not race, had a significant effect on overall survival (hazard ratio for high deprivation was 1.19 [95% Confidence interval 1.04 - 1.37], P = 0.01; Table). Progression-free survival on first-line chemotherapy was not different between the SES groups or racial groups in both univariate and multivariate analysis. Conclusions: The current study shows that patients from the high deprivation group (i.e., low SES), have worse survival in metastatic breast cancer. Race was no longer a significant predictor of survival when SES was accounted for in the analysis. This possibly suggests that poor outcomes in the African American population is explained by the association between low SES and African American race. Based on these results, there is an urgent need for healthcare investments in the low SES neighborhoods. [Table: see text]
Increasing Black patient participation in metastatic breast cancer clinical trials: The BECOME (Black Experience of Clinical Trials and Opportunities for Meaningful Engagement) project.
Authors: Walker Stephanie , Carlson Martha , White Carol B. , Howell John , Felder Tisha M. 
Published: June 2022

1014 Background: Among U.S. racial/ethnic groups, Black people with breast cancer have the highest death rate and shortest survival. Although ̃15% of cancer patients in the U.S. are Black, only 4-6% of clinical trial participants are Black. Only when trial participants reflect the diversity of the general population can oncologists understand how a drug works across subpopulations. The objectives of the BECOME initiative are to understand barriers to trial participation by Black patients with metastatic breast cancer (MBC) and to identify actions to increase participation. Methods: BECOME is sponsored by the Metastatic Breast Cancer Alliance, a consortium of representatives from nonprofit organizations, pharmaceutical/biotech companies, and patient advocates, many of whom are living with MBC. Findings from a literature review and Key Informant interviews informed a survey of U.S. adults living with MBC. Results: Of 424 survey respondents, 102 (24%) self-identified as Black. Black respondents’ trust and satisfaction with their oncology care team were high (> 90%), and 83% of Black respondents were somewhat or very likely to consider trial participation. However, 40% of Black respondents reported no one on their care team had discussed trials. Black respondents’ reasons to not participate in a trial included concerns about side effects (73%) and effectiveness (63%). Black respondents were more likely than non-Black respondents to believe unstudied treatments may be harmful (57% vs 31%). Black respondents were less likely than non-Black respondents to indicate they trust trials (73% vs 91%) and trust that people of all races/ethnicities get fair treatment in trials (32% vs 56%). Black respondents were more likely than non-Black respondents to value receiving trial information from someone with the same racial/ethnic identity (67% vs 10%), who has had breast cancer (73% vs 44%) or MBC (73% vs 51%), or who has been in a trial (72% vs 48%). Black respondents were also more likely to be motivated to participate to ensure people with their racial or ethnic identity will benefit (83% vs 51%). Conclusions: Black patients with MBC are willing to consider participating in clinical trials. Actionable steps to increase Black patient participation include: 1) enhancing awareness about trials by informing patients, increasing education, training healthcare providers to deliver patient-friendly information in an unbiased manner, and providing messaging from people of shared racial/ethnic identity and health experience; 2) building trust through clear communication; 3) addressing concerns about side effects, effectiveness, harm, and fair treatment; and 4) helping patients find and access trials. All stakeholder groups have a role to play in increasing Black patient participation in MBC clinical trials.
Detection of presumed germline pathogenic variants of hereditary breast cancer predisposition genes in circulating tumor DNA: SCRUM-Japan MONSTAR-SCREEN.
Authors: Hattori Masaya , Naito Yoichi , Yamanaka Takashi , Yasojima Hiroyuki , Nakamura Rikiya , Watanabe Junichiro , Yoshinami Tetsuhiro , Ozaki Yukinori , Fujisawa Takao , Nakamura Yoshiaki , Bando Hideaki , Yoshino Takayuki , Yamaguchi Rui , Imoto Issei , Iwata Hiroji 
Published: June 2022

1029 Background: Approximately 5-10% of breast cancer are hereditary. Variant allele frequency (VAF) of hereditary breast cancer predisposition genes in circulating tumor DNA (ctDNA) may be useful for detecting presumed germline pathogenic variants. Methods: One hundred and sixty-eight patients with advanced breast cancer (ABC) who underwent ctDNA and tumor tissue sequencing analyses in the SCRUM-Japan MONSTAR-SCREEN, a cancer genome screening project in Japan, from December 2019 to November 2021 were included. The patients were tested and monitored for their genomic alterations by FoundationOne Liquid assay or FoundationOne Liquid CDx assay. The pathogenic variants (PV) of hereditary breast cancer predisposition genes with VAF of 30% or higher in ctDNA were defined as PGPV. The VAF of BRCA1/2 on ctDNA analyses in BRCA1/2 germline pathogenic variant (GPV) carriers and the prevalence of PGPV in five hereditary breast cancer predisposition genes, including ATM, BRCA1, BRCA2, CHEK2, and PALB2, were investigated. Results: From 168 patients with ABC, including 115 Luminal, 32 HER2-positive, and 21 triple negative breast cancer, with a median age of 58 years, 39 PVs in 5 genes were identified with a median VAF of 0.62% (range: 0.1-84.77). ctDNA identified GPV of known BRCA1/2 GPV carriers (1 with BRCA1 and 6 with BRCA2) , with a median VAF of 51.4% (range: 48.2-77.5). The VAF of GPV on ctDNA were higher than 30% in subsequent consecutive samples. Among 161 patients with ABC, excluding 7 known BRCA1/2 GPV carriers, 6 PGPV (1 with BRCA1, 3 with BRCA2, and 2 with PALB2) were detected, with a median VAF of 65.5% (range: 51.2-84.8). Subsequent confirmatory tests were performed for two PGPV, and the variants were confirmed to be of germline origin. Conclusions: VAF on ctDNA analysis can help to easily detect PGPV of hereditary breast cancer predisposition genes. The PGPV detected in ctDNA analysis should be validated by established germline tests, and the results could provide opportunities for targeted therapies, as well as cancer risk assessment of patients and their relatives.
Pyrotinib in combination with metronomic oral vinorelbine in patients with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy: A single-center, single-arm, prospective phase 2 study.
Authors: Hao Chunfang , Wang Xu , Shi Yehui , Tong Zhongsheng , Li Shufen , Liu Xiaodong , Zhang Lan 
Published: June 2022

1033 Background: In 15% to 30% of breast cancers, human epidermal growth factor receptor 2 (HER2) is overexpressed, this is related to aggressive disease and poor prognosis. Although important clinical benefits for patients have been achieved by the use of the HER2 antibody trastuzumab, 50% to 74% of patients with metastatic disease have no response to treatment, and approximately 75% progress within one year. The purpose of this study was to evaluate the efficacy and safety of oral pyrotinib in combination with oral metronomic vinorelbine in patients with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy. Methods: This prospective phase 2 study enrolled patients aged 18-75 years with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy, and had an Eastern Cooperative Oncology Group performance score of 0-2. Patients received pyrotinib 400 mg once daily and vinorelbine 40 mg once on Monday, Wednesday, Friday of each week until disease progression or unacceptable toxicity. Both pyrotinib and vinorelbine were orally administered 30 min after meals. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease remission rate (DCR), overall survival (OS), quality of life (QoL) and safety (CTCAE 5.0). The follow-up of this study is ongoing, but enrolment is closed. This study is registered on Clinical Trials.gov, number NCT04903652. Results: Between Oct 21, 2019, and Jan 21, 2022, 36 patients were enrolled and all of them were included in the intent-to-treat (ITT) population. 20 of 36 patients had disease progress or death. Median follow-up was 16.23 months. The median PFS (mPFS) was 14.23 months (95% CI 8.13-20.33). The ORR and DCR were 38.9% and 83.3%, respectively. The median OS was not reached. Grade 3 adverse events (AEs) occurred in 17 of 36 patients, the most common were diarrhea 27.8% and stomachache 5.6%. No grade 4 AEs were observed. Conclusions: Pyrotinib combined with metronomic oral vinorelbine showed promising efficacy and manageable safety in patients with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy. This study might represent a potential treatment option for these patients. Clinical trial information: NCT04903652..
Monitoring and management of interstitial lung disease/pneumonitis among patients with metastatic breast cancer treated with trastuzumab deruxtecan.
Authors: Kish Jonathan K. , Mehta Sandhya , Kwong Jackie , Lam Clara , Falkenstein Angelica , Brown-Bickerstaff Cherrishe , Xiao Dong , Feinberg Bruce A. 
Published: June 2022

1036 Background: Trastuzumab Deruxtecan (T-DXd) was associated with an increased risk of interstitial lung disease (ILD)/pneumonitis (P) in metastatic breast cancer (mBC) patients (pts) in clinical trials, leading to ILD/P monitoring and management guidelines in the product label. This study aims to describe the monitoring and management of ILD/P during T-DXd therapy among US community oncology practices. Methods: Oncologists in the Cardinal Health Oncology Provider Extended Network (OPEN) participated in a cross-sectional survey on monitoring approaches for ILD/P among mBC pts. Participating physicians provided data from medical charts of up to 10 pts who were treated with T-DXd regarding presence of ILD/P symptoms, management, and outcomes of ILD/P symptoms. Results: Twenty-eight physicians from across the U.S participated and provided data on 149 T-DXd pts. Nearly all physicians reported they were monitoring ILD/P after T-DXd initiation by physical examination (n = 27), symptoms checklist (n = 25) and pulse oximetry (n = 23) at every visit, whereas fewer reported performing lung CT scan (n = 18), echocardiogram (n = 13), chest X-ray (n = 12), lung PET scan (n = 10), pulmonary function tests (n = 8) and diffusion testing (n = 7) on a less frequent basis. Among 149 T-DXd pts, 4 pts were diagnosed with ILD/P over an average T-DXd treatment duration of 5.5 months. All 4 cases initiated T-DXd treatment at 5.4mg/kg every 3 weeks, experienced ILD/P within the first 5 cycles of T-DXd, were diagnosed with lung CT scan and initially presented with Grade 2 symptomology (2 cases progressed to Grade 3). For both cases that remained as Grade 2, ILD/P completely resolved within 23 days. One case received IV methylprednisolone (1000mg daily; duration of therapy (DOT): 3 days) during hospitalization, oxygen therapy and T-DXd was permanently discontinued; whereas the other one received oral prednisone (started at 40mg daily and tapered to 5mg daily; DOT: 7 days) and T-DXd dose was held. For the two grade 3 cases, one received IV methylprednisolone (125mg daily; DOT: 7 days) during hospitalization, T-DXd dose was held, and ILD/P completely resolved within 11 days; whereas the other case received oral prednisone (started at 80mg daily and tapered to 5mg daily; DOT: 63 days), oxygen therapy, T-DXd was permanently discontinued, and ILD/P resolved with sequela within 46 days. Conclusions: ILD/P incidence in this small study sample of patients receiving T-DXd treatment was 2.7%. Although general awareness of ILD and routine screening by pulse oximetry and physical exam were common, management approaches for ILD/P were not always consistent with T-DXd prescribing information. Further physician education may be needed to improve appropriate management of ILD/P and outcomes for T-DXd pts.