bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benefits, harms, and burden of colorectal cancer screening among childhood cancer survivors previously treated with abdominal-pelvic radiation.
Authors: Yeh Jennifer M , Seguin Claudia L. , Whitton Jillian , Leisenring Wendy M. , Armstrong Gregory T. , Henderson Tara O. , Hudson Melissa M. , Nathan Paul C. , Neglia Joseph Philip , Oeffinger Kevin C. , Diller Lisa , Knudsen Amy B 
Published: June 2022

10015 Background: Survivors of childhood cancer treated with abdominal-pelvic radiation are at increased risk for colorectal cancer (CRC). The Children’s Oncology Group recommends early initiation of CRC screening at age 30, yet the benefits and burden are unknown. Methods: We used incidence and mortality data from the Childhood Cancer Survivor Study to modify the SimCRC model from the Cancer Intervention and Surveillance Modeling Network (CISNET) to reflect high CRC and competing mortality risks among survivors, assuming the elevated cancer risk arises from higher adenoma onset. Strategies evaluated varied by modality (no screening, colonoscopy, multitarget stool DNA [mtsDNA] testing, fecal immunochemical testing [FIT]), screening start age (25, 30, 35, 40, 45) and screening interval (every 3, 5 or 10 yrs for colonoscopy; every 1, 2 or 3 yrs for mtsDNA and FIT). Abnormal stool test results were followed up with colonoscopy. Screening performance and complication rates were based on published studies. Analyses assumed full uptake and adherence to all screening and follow-up procedures. To identify the optimal strategy for each modality, we estimated the number of colonoscopies required per additional life-year gained and compared it to benchmarks for screening strategies recommended by the US Preventive Services Task Force for average-risk individuals. Results: Among a simulated cohort of 20-yr-old 5-yr survivors with a history of abdominal-pelvic radiation, the cumulative CRC risk at age 50 was 0.8%, approximately twice that predicted among general population average-risk individuals (0.4%). In the absence of screening, 73 per 1000 survivors would be diagnosed with CRC in their lifetime and 29 would die from the disease. All screening strategies evaluated were estimated to yield substantial reductions in the lifetime number of CRC cases (45-71 cases averted per 1000) and deaths (23-28 deaths averted per 1000). The estimated lifetime number of colonoscopies ranged from 1781 to 14,625 per 1000. The lifetime number of colonoscopy complications was relatively low at 9 to 20 per 1000. Based on the burden-to-benefit ratios, colonoscopy every 10 yrs starting at age 30, mtsDNA every 3 yrs starting at age 30, or FIT every 3 yrs starting at age 25 were the optimal screening strategies identified (Table). Conclusions: Early initiation of screening may substantially reduce CRC mortality among high-risk childhood cancer survivors. These estimates of the balance of screening benefits and burden can inform follow-up care guidelines. [Table: see text]
Identifying trends for high symptom burden across the care continuum in adolescents and young adults (AYA) with hematologic malignancies.
Authors: Monick Sarah Elizabeth , Hanson Collin , Wang Amy Yuan , Lee Sang Mee , Hoehn Karen Sarah , Hlubocky Fay J. , Stock Wendy , Duvall Adam , McNeer Jennifer Lynn , Henderson Tara O. , Daugherty Christopher 
Published: June 2022

10019 Background: Cancer in adolescence and young adulthood is a non-normative life event associated with profound long-term physical and psychosocial consequences. Prior studies specifically demonstrate AYA patients with hematologic malignancies experience high symptom burden with poor quality of life. Here, we describe trends and factors associated with high symptom burden in patients treated at a multi-disciplinary AYA leukemia clinic at an academic medical center. Methods: The Edmonton Symptom Assessment Scale [ESAS] (measuring physical symptoms) and Brief Symptom Inventory-18 [BSI-18] (measuring psychological distress) were administered at baseline, 3 months, and 6 months from initial survey. Baseline demographic and treatment characteristics were collected. All patients had leukemia or lymphoma, were on treatment or in survivorship, and had access to a palliative care provider who was integrated into the clinic. Data was analyzed using Wilcox ranked sum test and linear mixed-effects model testing. Results: Of the 31 patients (median age 29 years, range 18-43) who completed surveys, 25 (80%) completed surveys at 6 months; 48% were female, 58% were white, 16% lived alone, 28% were single, 37% had children, 54% completed college, and 35% had an annual household income ≥ $75,000. Phases of care included 52% on intensive frontline/salvage treatment, 19% in maintenance (i.e. lower intensity) therapy, 16% as recent stem cell transplant (SCT) recipients (< 1 year since date of transplant), and 13% in survivorship. Overall, ESAS scores among patients were similar regardless of care phases; however, patients on frontline/salvage therapy reported higher fatigue than those in maintenance (p = 0.01). Moderate-severe symptoms (defined as ESAS > 3), including tiredness, anxiety, poor appetite, and poor feeling of well-being, were reported regardless of phase of care. At 6 months, there was no significant change in BSI-18 scores compared to baseline, while tiredness (p = 0.02), depression (p = 0.01), and constipation (p = 0.02) improved; no ESAS scores worsened. Age ≥ 30 was associated with worsening anxiety (p = 0.01) at 6 months vs baseline, while no statistically significant differences in ESAS scores were observed among race, education, relationship status, presence of children, living arrangement, or income. Conclusions: AYA patients with hematologic malignancies experience high symptom burden independent of demographic characteristics or phase of care. These findings highlight the need for standard symptom screening at each visit and the importance of incorporating supportive care throughout the continuum.
Predictors of differential outcomes according to response to induction chemotherapy in high-risk neuroblastoma.
Authors: Sokol Elizabeth , LaBarre Brian , Naranjo Arlene , Pinto Navin R. , Kreissman Susan G. , Granger Meaghan , Park Julie R. , Bagatell Rochelle , DuBois Steven G. 
Published: June 2022

10032 Background: Response to induction chemotherapy has been shown to predict outcome in patients with high risk neuroblastoma, with those achieving a complete response (CR) having superior outcomes. Little is known about what factors impact survival within groups of patients with favorable and unfavorable end-induction response. We evaluated whether conventional prognostic factors remain prognostic in subsets of patients defined by response to induction. Methods: Patients from four COG high risk trials (A3973, ANBL02P1, ANBL0532, and ANBL12P1) were included. End-induction response was determined according to the 1993 International Neuroblastoma Response Criteria (INRC). Patients were categorized as having end-induction responses of CR, partial response (PR) or better, less than PR without progressive disease (PD), and PD. Univariate Cox models calculated OS hazard ratios for clinical and biological variables in subsets defined by response category. Results: 1,244 patients were included. Among all patients, age >5 years, INSS stage 4 disease, adrenal primary site and unfavorable histology by INPC were associated with inferior OS (see Table). Among patients who achieved a CR, stage 4 disease was the only factor that remained significantly associated with worse OS. Among those who achieved PR or better, age >5 years, stage 4 disease and unfavorable histology remained significantly associated with inferior OS. For those with less than PR but without PD, adrenal primary site, MYCN amplification and 1p LOH were significantly associated with inferior OS. For those with PD, MYCN amplification and 1p LOH were associated with worse OS, but older age was associated with better OS. Conclusions: Specific prognostic factors in neuroblastoma are associated with differential survival in groups defined by response to induction. Age, stage, and histology appear to be associated with OS for patients with more favorable response to induction, whereas MYCN and 1p LOH play a greater role in patients with unfavorable response to induction. These data can help to further define prognosis for patients with variable responses to induction. [Table: see text]
Predicting outcomes with circulating adrenergic neuroblastoma mRNAs in children with relapsed and refractory neuroblastoma: A BEACON-Neuroblastoma biomarker study.
Authors: Moreno Lucas , Weston Rebekah , Viprey Virginie , Tchirkov Andrei , Corrias Maria , Lammens Tim , Gray Juliet , Owens Cormac , Laidler Jennifer , Gambart Marion , Castel Victoria , Van Eijkelenburg Natasha , Nysom Karsten , Laureys Genevieve , Castellano Aurora , Gerber Nicolas U. , Ladenstein Ruth Lydia , Valteau Couanet Dominique , Wheatley Keith , Burchill Susan A 
Published: June 2022

10039 Background: Children with relapsed and refractory neuroblastoma (RR-NBL) have poor outcomes. Early identification of children at greatest risk of relapse could mean timelier modifications of treatment to improve outcomes. High levels of adrenergic neuroblastoma mRNAs in blood of children with stage M neuroblastoma receiving frontline treatment predict poor outcome (Viprey PMID: 24590653). Since these markers have not been thoroughly studied in the RR-NBL population, we have prospectively evaluated the prognostic potential of the adrenergic neuroblastoma mRNAs paired-like homeobox 2B (PHOX2B ) and tyrosine hydroxylase (TH) in blood from children with RR-NBL treated in the BEACON-Neuroblastoma trial (NCT02308527). Methods: Blood samples collected at baseline from 88 children were analysed by reverse transcriptase polymerase chain reaction (RTqPCR) for PHOX2B and TH mRNAs. The prognostic power of these mRNAs was evaluated using Kaplan-Meier survival curves and Cox proportional hazards regression. Progression-free (PFS) and overall survival (OS) were calculated from the date that the blood sample was taken at screening to the date of an event; progression, disease recurrence, death or censored alive at the last clinical evaluation. Results: Of the children in this cohort, 58 (66%) had relapsed and 30 (34%) had refractory disease. Twenty-three (26%) had MYC-N amplified tumours. TH and PHOX2B mRNAs were detected in 55% and 60% of blood samples respectively; the correlation coefficient between TH and PHOX2B was 0.75. Higher levels of TH, PHOX2B mRNAs or both combined were associated with reduced PFS and OS (Table). For TH, median PFS for children with TH levels below the median was 12 months (95%CI, 4.6–13 months) versus 5.5 months (95%CI, 1.8–9.4 months) for those children with TH levels above the median. For PHOX2B, median PFS for children with PHOX2B levels below the median was 11.5 months (95%CI, 7.6–34 months), compared to 5.7 months (95%CI, 1.8–10.5 months) where levels were above the median. Conclusions: TH and PHOX2B mRNAs in blood collected at baseline identify children with refractory or relapsed neuroblastoma at greatest risk of progression or death. In the RR-NBL setting, this simple blood test could be used to stratify treatment strategies. Clinical trial information: NCT02308527. [Table: see text]
Protein, fat, and animal food intakes and premature aging in adult survivors of childhood cancer: St. Jude Lifetime (SJLIFE) cohort.
Authors: Park Yikyung , Williams AnnaLynn , Finch Emily R , Lanctot Jennifer Q. , Jiang Shu , Krull Kevin R. , Armstrong Gregory T. , Hudson Melissa M. , Colditz Graham A. , Robison Leslie L. , Ness Kirsten K. 
Published: June 2022

10055 Background: Childhood cancer survivors are a growing population who appear to be at higher risk for premature aging and age-related chronic health conditions than their peers with no history of cancer. Diet affects many hallmarks of aging, such as inflammation, metabolic dysfunctions, and molecular and epigenetic changes, leading to impairment in physical and cognitive functions and premature death. High consumption of animal foods that are high in protein and fat increase risk for many age-related chronic diseases. However, some studies found protein intake was beneficial for physical frailty in elderly and cancer survivors. Methods: Adult survivors (> = 18 years old) of childhood cancer survivors enrolled in the SJLIFE Cohort between 2007 and 2017 completed a 110-item food frequency questionnaire at study entry (n = 3,322). Survivors’ sociodemographic, cancer, cancer treatments, and medical history data were abstracted from medical records. Health conditions self-reported after cancer diagnosis were clinically validated. Premature aging was assessed using the Deficit Accumulation Index (DAI) based on 45 aging-related health conditions. DAI is categorized into low (< 0.2), medium (0.2-0.34) and high (> 0.35) aging risk groups. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multinomial logistic regressions adjusting for potential confounders. Results: The average age of survivors at baseline was 31 years. Approximately half of the survivors were women, and 82% were white, non-Hispanic. 20% and 8% of survivors were at medium and high risk for aging, respectively. Survivors at high risk for aging tended to be female, smokers, have low socioeconomic status, and received radiation therapy to head and neck, chest, spine or abdomen compared to those at low aging risk. Higher protein intake was associated with a less risk of premature aging (OR = 0.74, 95% CI: 0.58-0.95 for high aging risk group; OR = 0.91, 95% CI: 0.78-1.07 for medium aging risk group, per increment of 5% of total energy intake). On the other hand, higher fat intake was related to an increased risk of premature aging (OR = 1.14, 95% CI: 1.01-1.29 for high aging risk group; OR = 0.99, 95% CI: 0.91-1.08 for medium aging risk group, per increment of 5% of total energy intake). However, substituting monounsaturated fat for other types of fat was associated with a lower risk of premature aging (OR = 0.81 95% CI: 0.70-0.95 for high aging risk group). Red meat (OR = 1.11, 95% CI: 0.87-1.42 for high aging risk group) and dairy intake (OR = 0.99, 95% CI: 0.72-1.38 for high aging risk group) was not related to risk of premature aging. Conclusions: Consuming protein and fat from healthy foods may lower the risk of premature aging in childhood cancer survivors.
Survival in patients with breast cancer and history of autoimmune disease.
Authors: Dedousis Demitrios , Zhang Annie , Vassiliou Anastasia , Cao Shufen , Yammani Deepthi , Kyasaram Ravi Kumar , Shanahan John , Keinath Melissa C. , Hsu Melinda Laine , Fu Pingfu , Dowlati Afshin , Montero Alberto J. 
Published: June 2022

1020 Background: Patients with autoimmune disease, specifically systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjogren syndrome, are at reduced risk of developing breast cancer compared to those without a prior history of autoimmune disease. Despite this, little is known about the survival of patients with concurrent autoimmune disease and breast cancer. This study compared outcomes in patients with breast cancer with and without autoimmune disease. Methods: This study was a retrospective analysis of patients from SEER-Medicare databases from 2007-2014 with breast cancer. Patients with a history of autoimmune disease were identified using ICD-9 codes. The effects of autoimmune disease on overall survival (OS) and cancer-specific survival (CSS) were estimated using multivariable Cox regression and Gray’s method respectively controlling the effects of age, race and chronic kidney disease (CKD). The cumulative CSS was estimated taking death as a competing risk. Results: The overall prevalence of investigated autoimmune diseases among the 137,324 patients with breast cancer was 26.69%. The most common autoimmune diseases identified were RA (23.35%), psoriasis (2.41%) and SLE (1.12%). In stage IV breast cancer patients the OS and CSS were significantly higher in patients with autoimmune disease (p values < 0.0001), with a median OS of 36 months compared to 30 months in patients without autoimmune disease. After adjusting for the effects of age, race, and CKD, autoimmune disease was still predictive of higher OS (HR: 1.46, 95% CI: 1.37 – 1.57, p < 0.0001) and CSS (HR: 1.39, 95% CI: 1.29 – 1.5, p < 0.0001). Patients with autoimmune disease and stage I-III breast cancer, had lower OS (p < 0.0001, p < 0.0001, and p = 0.026 respectively) compared to patients without autoimmune disease. Conclusions: We found a higher prevalence of RA, Crohn disease, ulcerative colitis, and SLE in patients with breast cancer compared to cohorts of similar age ranges in the general population. History of autoimmune disease resulted in significantly improved OS and CSS in patients with stage IV breast cancer even when controlling for age, race and CKD, in this pre-immunotherapy cohort. These results suggest that that anti-tumor immunity plays an important role in late-stage breast cancer, and could be potentially exploited to improve the effectiveness of immunotherapy. Further research into the relationship between autoimmunity and breast cancer is warranted.
The mutational profile of ER-, PR+, HER2- metastatic breast cancer.
Authors: Fischbach Neal A. , Huang Richard S.P. , Lustberg Maryam B. , Pelletier Maureen , Pusztai Lajos , Sivakumar Smruthy , Sokol Ethan , Ross Jeffrey S. , Levy Mia Alyce 
Published: June 2022

1025 Background: ER-PR+Her2- breast cancer is a rare subtype occurring at approximately 1% of all breast carcinomas. Most of these cancers behave in an aggressive fashion with limited benefit from anti estrogen therapy, similar to triple negative breast cancer (TNBC). Better characterization of these tumors is needed for predicting clinical behavior, response to endocrine therapy, and eligibility for clinical trials. Here we sought to evaluate the mutational profile of a well curated set of ER-PR+HER2- metastatic breast cancers and compare to other receptor phenotypes. Methods: 2049 consecutive breast cancers submitted to Foundation Medicine for comprehensive genomic profiling (CGP) were included. ER, PR and HER2 expression were abstracted from submitted pathology reports. Cases without complete ER, PR and HER2 information in pathology reports were excluded. CGP was performed as previously described (Frampton, 2013). Results: Patient ages were similar across subgroups. Generally, ER-PR+HER2- tumors were rare (n = 23, 1.1%) and most similar to TNBC in their genomic profiles. These tumors harbored high rates of TP53 and BRCA1 alterations and low rates of PIK3CA, ESR1, and CDH1 alterations. Genomic loss of heterozygosity (gLOH) was similar in the ER-PR+HER2- and ER+PR+HER2-subtypes (8.18% and 8.66% respectively), and lower than TNBC (17.19%). Notably, a high rate of RB1 alterations were identified in the ER-PR+HER2- patients (13%, 3/23), numerically higher than the other subtypes. EGFR, MET, PTEN, CDKN2A and KRAS alterations were also observed at a higher frequency in ER-PR+Her2- cancers (8.7, 4.2, 39.1, 13.0 and 13.0% respectively) relative to the other subtypes. IO drug biomarkers including MSI, TMB and PD-L1 IHC were similar among the groups. Conclusions: The mutational profile for ER-PR+Her2- metastatic breast cancer more closely resembles TNBC than ER+ breast cancer. These data suggest molecular profiling may be a useful adjunct to optimize treatment strategies for this rare subset of cancers. Based on molecular characteristics, we recommend including ER-PR+Her2- patients in clinical trials for TNBC. Finally, genes including RB1, CKDN2A, PTEN, EGFR and MET are mutated at higher frequency in ER-PR+Her2- cancers than other subsets, suggesting unique biology with potential therapeutic implications. [Table: see text]
A phase II, single-arm, open label, Simon two-stage study of pembrolizumab in patients with metastatic HER2-negative breast cancer: Evaluation of impact of germline variants in APOBEC3B (AUROR).
Authors: Ho Gwo Fuang , Lee Soo-Chin , Lim Joanna , Bustam Anita Zarina , Lim Siew Eng , Saad Marniza , Ow Samuel Guan Wei , Ngoi Natalie , Abdul Satar Nur Fadhlina , Malik Rozita Abdul , Alip Adlinda , Law Kian Boon , Toh Yok Yong , Pan Jia Wern , Teo Soo Hwang 
Published: June 2022

1026 Background: A germline deletion in the APOBEC3B cytosine deaminase gene [A3Bdel] occurs more frequently in Asian women (45% heterozygous deletion (hetD) and 15% homozygous deletion (homD)) compared to in Caucasian women (15% hetD and 4% homD). Carriers are more likely to develop breast cancer, and cancers in carriers are more likely to have a hypermutator phenotype (with C > T transitions) and to be immune-enriched. In this clinical trial, we aim to evaluate whether the immune activation increases response to checkpoint immunotherapy. Methods: In this open label, single arm Phase II study of single agent pembrolizumab in metastatic HER2-receptor negative breast cancer patients with germline deletion in A3B, 40 evaluable subjects who have received > = 1 but < = 3 lines of therapy in a metastatic setting will be enrolled and given pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations (2 years), with Objective Response Rate (ORR) using RECIST 1.1 as the primary study endpoint. The study applies a Simon two-stage design, where if at least 3 out of 22 evaluable patients achieve CR/PR in stage I, the study will proceed to stage II. Results: To date, 84 breast cancer patients were screened for germline A3Bdel, of whom 46 (54.8%) were heterozygous carriers and 12 (14.3%) were homozygous carriers. The study enrolled 22 female A3Bdel carriers with a median age of 59.4 years (range: 32.1, 82.9 years) between September 2020 and September 2021 for stage I analysis. On average, patients received 2 prior lines of chemotherapy in a metastatic setting [6 with 1, 8 with 2 and 8 with 3 lines of prior chemotherapy]. Complete response (CR) was observed in one patient, while partial response (PR) was observed in 4 patients, with an ORR of 22.7% (5 over 22 subjects) in stage I, meeting the pre-defined criteria to proceed to stage II. Notably, the patient with complete response had received 2 prior lines of chemotherapy, whereas of the patients with partial response, 1 had received 1 prior line and 3 had received 3 prior lines of chemotherapy in a metastatic setting. As the observed ORR was greater than the value of r1 (13.6%), the study has met the statistical criteria to proceed to the stage II enrolment with an additional 18 patients required to complete the entire study. Conclusions: Single agent pembrolizumab demonstrates promising efficacy in germline A3Bdel carriers, who constitute almost two-thirds of Asian patients. Clinical trial information: NCT03989089.