bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and efficacy of naxitamab plus modified dosing of GM-CSF for patients with high-risk neuroblastoma (HR-NB) in first complete remission (CR) or with primary refractory disease.
Authors: Kushner Brian H. , Modak Shakeel , Basu Ellen M. , Iglesias Cardenas Fiorella , Kramer Kim , Roberts Stephen S. , Cheung Nai-Kong V.
Published: June 2023

e22012

Background: In an international trial, the humanized anti-GD2 antibody naxitamab+GM-CSF was effective against chemo-resistant HR-NB, leading to approval by the Food and Drug Administration. We subsequently modified GM-CSF dosing based on a shortened priming period and pharmacokinetics showing prolonged T½ of naxitamab. We investigated safety and efficacy of naxitamab plus GM-CSF administered by a novel schedule in HR-NB patients treated in 1st CR (Group 1) or with primary refractory disease in bones and/or bone marrow (BM) (Group 2). Methods: Immunotherapy was administered q1-2 months up to 5 cycles in Group 1 and ≥5 cycles after major responses in Group 2. Naxitamab was infused intravenously (30-90”) on days 1/Monday-3/Wednesday-5/Friday (i.e., 3 doses/cycle), 3mg/kg/infusion (9mg/kg/cycle, i.e., ~270mg/m2/cycle). Previously, priming doses of GM-CSF 250µg/m2/day were subcutaneously-administered x5 (days -4 to 0), followed by a step-up to 500µg/m2/day x5 (days 1-to-5), but now priming doses were x3 days (days -2 to 0 [Friday-Saturday-Sunday]) and stepped-up dosing was x7 (days 1-to-7 [Monday-to-Sunday]), i.e., through 2 days after the last dose of naxitamab. Patients did not receive isotretinoin. Follow-up was from start of naxitamab through 1/15/23. Results: From 2/22/2021-to-12/15/22, 59 patients (32 Group 1, 27 Group 2) received 1-10 (median 5) cycles, total 250. No unexpected toxicities occurred. No patient had to discontinue GM-CSF. Treatment was outpatient, except 3 patients with hypertension. Cycles were aborted because of viral symptoms (n=3), suspected small bowel obstruction (n=3), hypoxia (n=2), and hyperbilirubinemia (n=1). Four patients received only ½ of dose 1 in cycle 1 because of agitation or hypotension. In Group 1, 4/32 patients relapsed at 4-5 months while 28 patients remain in CR at 1+-to-22+ (median 15+) months. In Group 2, disease sites and responses were: BM alone (n=7): CR in 6 (1 later relapsed); MIBG alone (Curie scores 1-11) (n=8): 1 partial response, 1 progressive disease, 2 stable (1 later relapsed), 4 non-evaluable because of radiotherapy; MIBG (Curie scores 1-26) and BM(+) (n=12): 7 CR (3 later relapsed), 4 PR, 1 stable disease (subsequently progressed). Conclusions: This large experience confirms that the new schedule is safe and, despite short follow-up, appears as effective as the prior schedule.
Molecular pathways involved in hepatoblastoma tumorigenesis in trisomy 18.
Authors: Schepers Emily , Glaser Kathryn , Zwolshen Harrison , Bondoc Alexander
Published: June 2023

e22015

Background: Trisomy 18 (T18) is the second most common aneuploidy caused by additional copies of chromosome 18. It occurs at a rate of 1 in 2000-6000 live births, with current 1-year survival rates between 5-10% of live births. Meta-analysis of tumor in T18 patients revealed 67 tumors, with 44 (66%) being HB. The contribution of underlying genetic alterations to tumorigenesis is incompletely understood. There is a reversed gender ratio in children with T18 and HB as well as more favorable histology and response to treatment. These suggest an alternative molecular pathway in these cases might promote tumorigenesis. Although there is an association between trisomy 18 and hepatoblastoma, the cause of this increased incidence is unknown. We hypothesize that SMAD4/TGFβ signaling in conjunction with canonical Wnt signaling has a role in T18 HB tumor development as well as a more fetal tumor histology. Methods: Seven patients with T18 were treated at CCHMC for HB. Five patient samples were collected at time of surgery for evaluation. Patient samples and data were collected with informed consent and institutional IRB approval. We performed transcriptomic analysis using RNA bulk sequencing data for five paired background and tumor samples. Further gene and protein expression were evaluated and compared to non-syndromic patients with HB. Histologic evaluation for tumor subtype and target proteins was performed. Results: Of the seven patients evaluated, six (85.7%) were female with a median age of diagnosis of 9 months. All patients underwent hepatectomy, with final pathology demonstrating predominantly fetal histology. All patients are currently in remission. Bulk RNAseq demonstrated upregulation of SMAD4 and TGFβ, as well as upregulation of canonical Wnt signaling pathway including Wnt3 and transcription factors Lef1, TCF4, and APC in tumor of T18 patients compared to background and non-syndromic HB patients. β-catenin immunostaining demonstrates increased or stabilized expression in tumor compared to background liver consistent with non-syndromic HB. Conclusions: We have identified a novel tumorigenic mechanism of HB in T18. Upregulation of SMAD4 in T18 results in increased TGFβ signaling, with potential crosstalk between SMAD4/TGFβ and Wnt/β-catenin signaling promoting cancer development. Further evaluation is required to understand the pathway crosstalk and impact of genetic mutation on pathway regulation.
Outcome of nasopharyngeal carcinoma (epithelial undifferentiated NOS) in children and adolescents: SEER database analysis.
Authors: Pendharkar Dinesh , Nirmal Garima , Ali Adnan , Gupta Neha
Published: June 2023

e22016

Background: Nasopharyngeal carcinoma (NPC) is a rare malignant epithelial tumor of the nasopharynx and account for less than 1% of childhood tumors. Undifferentiated epithelial tumors are one of the commonest histologies. This study aimed to demonstrate the characteristics and outcome of NPC in children and adolescents. Methods: The Surveillance, Epidemiology and End Results database (SEER Research Data 18 Registries Nov 2020Sub (2000-2018)was analyzed for patients diagnosed with carcinoma undifferentiated NOS, NPC ( ICD-O-WHO-3 code 8020). Patients were excluded if the cause of death was not associated with their cancer according to SEER’s cancer-specific death categorization. Overall Survival were estimated using the Kaplan-Meier method, and variables were compared using the log-rank test. P values < .05 were considered significant. Results: A total of 62 patients aged ≤19 years with undifferentiated nasopharyngeal carcinoma were identified. The cohort included 39 (62.9%) males and 23 (37.1%) females .Among them, 40.3 % were white, 40.3% were black,17.7% were Asians/Pacific Islanders, and 1.6% were American Indian. The age of diagnosis distribution included 2 (3.2%)children with 5-9 year, 17 (27.4%) children with 10-14 years and 43(69.4%) children with 15-19 years. With a median follow up of 7.9 years, 3 year OS of the entire cohort was 84.5%. 3 year OS for children aged ≤14 years was 82.1% and for children aged 15-19 years was 85.5% (p- value = 0.649). When stratified by treatment era, the 3-year OS of all patients treated after 2009 was not statistically significant than those treated before (3-year OS, 85.5% vs 82%, P = .0649). Conclusions: Children and adolescents with undifferentiated epithelial neoplasm NOS, NPC had excellent survival. Age and treatment era has no prognostic impact on outcomes.
Pediatric carcinoid tumors of the lungs: A descriptive analysis.
Authors: Lee Dong-jin Joshua , Largen Joseph , Abid Kaamil , Hu Robert W.
Published: June 2023

e22017

Background: From 1973 to 2012, the prevalence of neuroendocrine tumors in children was found to have increased by approximately 6-fold when using the Surveillance Epidemiology, and End Results. While carcinoid tumors in adults are mostly indolent, pediatric carcinoid tumors tend to carry worse prognoses. Our goal for this study is to describe the population of pediatric patients with pulmonary carcinoid tumors. Methods: We used the National Cancer Database to identify pediatric patients diagnosed with carcinoid tumors of the lungs between 2004-2020. Analysis was conducted with SPSS to determine frequency of cases in different demographics. Survival was assessed using Kaplan-Meier curves with significance set at p < 0.05. Results: Of the 125 patients identified, 55% of the patients were male and 45% female. Pulmonary carcinoid tumor patients were predominately white accounting for 80% of all cases. Black patients accounted for 14% of cases. The ages of diagnosis ranged from 3-17 years of age with the mean being 14.5 years of age. The majority of patients were diagnosed during their teenage years–84% were between the ages of 13 and 17 at diagnosis. Only one case was observed in a patient of age 6 or under. The median survival was 89 months. Univariate analysis revealed no significant difference in survival was seen in sex, race, or insurance groups. Charlson-Deyo score, however, did impact survival, where patients with a score of 2 had lower median survival time (36 months) compared to patients with a score of 1 (121 months) or 0 (87 months). Conclusions: Pediatric pulmonary carcinoid tumors are more commonly seen in white patients with most diagnoses occurring during patients’ teenage years (13-17). Age, sex, and race did not have a significant effect on survival although a Charlson-Deyo score of 2 was indicative of a worse prognosis when compared to a score of 1 or 0.
Cardiac iron overload in pediatric oncology and bone marrow transplant survivors.
Authors: Hans Rhea , Cleveland Celeste , Shah Sanjay , Wisotzkey Bethany , Walsh Alexandra Maria
Published: June 2023

e22022

Background: Cardiovascular late effects are a leading cause of mortality and morbidity in childhood cancer and Bone Marrow Transplant (BMT) survivors. In patients receiving chronic red blood cell transfusions, excess iron may be deposited in the liver, heart, and pituitary gland. Iron overload cardiomyopathy is characterized as a restrictive physiology with early diastolic dysfunction ultimately progressing to end-stage dilated cardiomyopathy. Iron loading in the heart can also lead to arrhythmias and increase myocardial ischemia reperfusion injury due to increased formation of reactive oxygen species. It is not yet known whether high transfused packed red blood cell (PRBC) volumes in cancer and BMT patients leads to cardiac iron deposition, and whether iron-induced cardiac injury contributes to the known cardiovascular late effects in these patients. Methods: 83 childhood cancer and BMT survivors with elevated serum ferritin levels and subsequent liver Magnetic Resonance (MR) imaging were identified. 18 patients (21.7%) who had liver iron content of > 12mg/g (mean 16.0 ± 7.36 mg/g) also underwent Cardiac MRI (CMR) to determine cardiac iron content. Results: Median transfused blood volume was 393 ml/kg [95% Confidence Interval (CI) 170-780 ml/kg]. All 18 patients had at least one echocardiogram showing normal ventricular ejection fractions [mean 65.1 ± Standard Deviation (SD) 3.53%] and normal shortening fractions (mean 35.4 ± 3.67%). All patients had myocardial iron content within normal ranges (T2* relaxation time mean 35.1 msec ± 7.1 [normal >20 msec], mean ± SD iron content 0.63± 0.2 mg/g dry weight, range 0.5-1.1). There was no association of cardiac iron content with transfused blood volume, anthracycline dose (mg/m2) or liver iron content (Pearson Correlation Coefficients 0.27, 0.29 and 0.89 respectively). Conclusions: Childhood cancer and BMT patients receive multiple PRBC transfusions to treat symptomatic anemia. It is currently unknown whether excess iron deposition in the heart contributes to the cardiac effects of impaired diastolic function and ultimately systolic dysfunction. In this study, 11 of 18 patients (61.1%) with high levels of liver iron had at least 1 other risk factor for the development of future cardiac dysfunction (either anthracycline exposure, radiation to the chest or total body irradiation or both). Larger studies are needed to determine whether oncology patients with high levels of iron deposition in their liver are also at risk for clinically significant cardiac iron loading, and what risk factors may exist for elevated myocardial iron content.
SARS-CoV2 vaccination response in pediatric oncology patients.
Authors: D'Souza Amber Marie , Gnanamony Manu , Thomas Maria , Nguyen Thu Hien , de Alarcon Pedro Antonio
Published: June 2023

e22023

Background: There remains limited knowledge about the immune response to SARS-COV2 vaccination in pediatric oncology patients, which is essential to provide appropriate counseling and risk adaptation in this vulnerable population. The goal of this study was to understand immunogenicity after vaccination in pediatric oncology patients and determine if certain clinical factors impacted response. Methods: After institutional review board approval, we consented patients in our clinic who had diagnosis of cancer, were 0-25 years old, and actively receiving therapy, including chemotherapy, immunotherapy, and targeted therapy. We excluded patients who were completely vaccinated prior to their cancer diagnosis. Blood samples were collected pre-vaccination, as well as 2, 6, and 8-12 weeks after vaccination. Healthy children who were fully vaccinated could also consent as controls, with samples collected up to 6 months from vaccination. Demographic data, history of COVID19 infection, and complete blood counts around time of vaccination were collected. To study immunogenicity, we measured neutralizing antibodies by enzyme-linked immunoassay (ELISA, GenScript) and interferon gamma (INFl) secretion, which measures T cell response to viral antigens, by enzyme-linked immunospot (ELISPOT, Mabtech). Results: 16 patients enrolled on study, for which 11 were evaluable along with 7 control patients. Seven patients had acute lymphoblastic leukemia, two had sarcomas, one had chronic myeloid leukemia, and one had Hodgkin lymphoma. Overall, the pediatric oncology patients had a worse immune response to vaccination compared to controls. Only one patient, who had COVID19 prior to vaccination, had similar responses to controls. Patients were divided into inadequate (n = 6) and adequate response (n = 5) based on semiquantitative analysis of immune response at 8-12 weeks post vaccination. Inadequate response was primarily seen in acute lymphoblastic leukemia patients (5 of 6 patients) and those receiving highly cytotoxic chemotherapy. Adequate response was seen in patients receiving oral therapy or chemoimmunotherapy. No patients received steroids around the time of vaccination. The inadequate response group had the lowest absolute lymphocyte counts (ALC), but ALC was variable in the adequate response group. Numbers were too small to note a difference based on age, gender, ethnicity, or type of vaccine. Conclusions: Pediatric oncology patients have a suboptimal immune response to SARS-COV2 vaccination. Malignancy type, therapy modality, and to a lesser extent, ALC at the time of vaccination, are all associated with worse immunogenicity. This study supports the need for additional doses and boosters to provide better protection against COVID19 in pediatric oncology patients.
Rates of colorectal cancer screening versus lung cancer screening: Where does the problem lie?
Authors: Menakuru Sasmith R. , Salih Ahmed , Dhillon Vijaypal S. , Hanna Nasser H.
Published: June 2023

e22504

Background: In 2021, the U.S. Preventive Services Task Force recommended expanding the population who should undergo routine lung or colorectal cancer screening to include those between 50 and 80, with a 20-pack or more smoking history, and those who are currently smoking or have quit within the last 15 years. According to the Centers for Disease Control, 74.3% of the at-risk population undergo colorectal cancer screening. In contrast, according to the American Lung Association, only 5.8% of the eligible population undergoes lung cancer screening. Methods: This is a retrospective analysis of 158 patients who underwent colorectal cancer screening by colonoscopy between July 2022 and October 2022 at a high-volume hospital in Indiana. Patients were followed up in their primary care office between November 2022 and January 2023 to assess if they had also met the screening criteria for lung cancer with a low dose computed tomography (LDCT) scan. Patients who met the lung screening criteria were interviewed at their subsequent primary care appointment to evaluate their knowledge, attitudes, and compliance with lung cancer screening. Results: Of the 158 participants, 86 (54.4%) met the criteria for lung cancer screening with a LDCT. Only 5 (5.8%) of the eligible subjects underwent LDCT screening. 72 of the 81 patients who were not screened for lung cancer had scheduled follow-ups with their primary care provider during the study time frame. Of these 72 patients, 45 (62.5%) lacked knowledge about LDCT and lung cancer screening, despite meeting the criteria for it. 22 (30.5%) did not think they needed a LDCT, and 5 (6.9%) had no interest in screening despite previous awareness. All 72 patients who had colorectal cancer screening but not lung cancer screening were asked why they underwent the former but not the latter. 68 (94.4%) indicated that colonoscopy was recommended to them and that they knew someone in their families who had it done. Conclusions: Colon cancer screening rates remain high compared to lung cancer screening rates in an at-risk population. A lack of knowledge from patients is the primary reason for not receiving LDCT, despite receiving colon cancer screening.
Skin cancer screening and sun safety education program for high school students in southern California.
Authors: Savage David James , Gilbertson Riley
Published: June 2023

e22505

Background: Decreasing unprotected exposure to ultraviolet (UV) radiation during childhood can significantly decrease the risk of developing skin cancer as an adult. School-based sun safety curricula have demonstrated efficacy in teaching young adults about the harms of prolonged, unprotected UV exposure and have been effective in increasing safety practices. This project provided a 50-min sun safety curriculum to high school students at a public high school in San Diego, CA just prior to the summer break in 2022. The curriculum addressed skin cancer risk factors, skin protection methods, the benefits of limiting lifetime UV exposure, and methods for performing a skin self exam. The study objective was to assess sun safety knowledge before and after the class, and measure behavior changes three months thereafter when students returned from summer break. Methods: The sun safety classes were taught in groups of 40-60 students across six class periods in June 2022. Students were asked to complete an anonymous pre-participation online survey assessing their knowledge of common skin cancer types and skin cancer risk factors. Students were taught the curriculum over 45 minutes with 5 minutes reserved for questions. Two follow-ups surveys were conducted with the students, one at the end of the class period and a second follow-up three months later. Follow-up surveys assessed retention of knowledge and changes in sun safety behavior. Students had the option of providing a cell phone number so they could be contacted to participate in the second follow-up survey. Results: The curriculum was taught to nine classes of approximately 300 students in a single day across six class periods. A total of 206 students completed the pre-participation survey. At the first follow-up, 95.1% of students completed the post-participation survey and students showed significant improvement in knowledge of common skin cancer types (12.6% pre-participation to 68.9% post-participation), skin cancer risk factors (11.2% pre-participation to 16.8% post-participation), and skin cancer prevention methods (22.8% pre-participation to 45.9% post-participation). For the second follow-up, 128 students provided contact information and the survey had a response rate of 71.5%. After 3 months, students demonstrated retention of knowledge of skin cancer types and risk factors. A majority (87.2%) of students indicated that their use of sunscreen had increased and 57.4% indicated that their use of sun protective barriers had increased over the summer because of this course. Conclusions: This pilot course demonstrates that targeted sun safety education for teenagers before summer break can significantly increase sun safety awareness, adoption of protective behaviors, and knowledge about skin cancer. Such an intervention can promote skin cancer awareness at a young age where behavior changes can decrease lifetime risk of skin cancer.
Breast malignancy after radioactive iodine ablation for thyroid pathology: A systematic review of the literature.
Authors: Yellamaty Victoria , Hamid Yumna , Efiom-Ekaha Daniel N.
Published: June 2023

e22511

Background: Radioactive Iodine Ablation (RAI) is a procedure in which the administration of radioactive iodine is utilized to eradicate pathologic thyroid tissue. RAI is commonly used for thyroid malignancy and hyperthyroidism. Although RAI has been a mainstay of treatment for these diseases, there has been some controversy regarding the development of secondary primary malignancy after RAI. Breast cancer is a particular concern. As breast cancer is the second most common cancer for women in the United States, understanding its risk factors is a key component of public health. Methods: A systematic review was conducted following PRISMA guidelines. Inclusion criteria consisted of English language studies that evaluated the association between radioactive iodine ablation and secondary primary breast malignancy. The study was conducted from January 2023 until February 2023. Two independent researchers conducted the literature search utilizing PubMed, SCOPUS, JSTOR, and Wiley Library using standardized search terms. The titles and abstracts of these studies were independently screened, and further evaluated for relevancy. Qualitative data was then extracted and summarized. Results: Of the 386 manuscripts retrieved, 27 met inclusion criteria. These studies were published between 1983 – 2022. Of these, 15 articles reported no association between RAI and the development of secondary primary breast malignancy. Of the manuscripts which reported no association, 6 examined RAI for hyperthyroidism, and 9 examined RAI for thyroid malignancy. 12 studies reported an association between RAI and the development of secondary primary breast malignancy. Of the studies reporting an association, 1 examined RAI for hyperthyroidism, and the remaining 11 examined RAI for thyroid malignancy. For the single study that found an association in the case of hyperthyroidism, the researchers found a dose-dependent relationship. Conclusions: The literature surrounding secondary primary breast malignancy after RAI is controversial. This systematic review resulted in conflicting data regarding the association between radioactive iodine ablation for thyroid pathology and the development of secondary primary breast malignancy. The studies that suggested an association between RAI and secondary primary breast malignancy were overwhelmingly studies in which RAI was used for the treatment of thyroid malignancy. Some studies suggest a possible dose-dependent relationship between RAI and secondary primary breast malignancy, however this data is limited. Additional studies would be beneficial to address this gap in the literature.
Obesity and triple negative breast cancer diagnosis among premenopausal women.
Authors: Taylor Caitlin , Sheen Melanie Anne , Cattie Rabia , Chung Victoria , Henry Marcia , Olet Susan , Alberti Matthew , Yuan Helen , Peeples James , Saxena Raina
Published: June 2023

e22513

Background: Obesity is a known risk factor for the development of postmenopausal breast cancer, specifically hormone-receptor positive breast cancer, and is associated with poor outcomes and decreased overall survival. While obesity in pre-menopausal patients is thought to be protective against the development of breast cancer, application across breast cancer subtypes remains less clear. Methods: We performed a retrospective analysis of 758 patients under 40 years of age diagnosed with breast cancer at our institution over 10 years. Variables including age at diagnosis, breast cancer subtype, race and BMI were evaluated. To assess the association between body mass index (BMI), race and triple negative breast cancer (TNBC), odds ratios (OR) and their associated 95% Confidence interval (CI) OR are reported. Results: Obese patients (BMI >30) were more likely to have TNBC compared with non-obese patients [OR=1.46, 95% CI [1.07 – 2.00), P=0.0161]. Black patients had a twofold likelihood of having TNBC compared with white patients regardless of BMI [OR=2.16, 95% CI [1.56 – 2.97), P<0.0001]. Conclusions: Obese patients under 40 years of age were more likely to be diagnosed with TNBC than non-obese patients. Our data highlights ongoing disparities among TNBC diagnosis and emphasizes the importance of weight loss interventions targeted towards premenopausal women at high risk for breast cancer. [Table: see text]
Patient-provider communication factors associated with mt-sDNA screening for colorectal cancer.
Authors: Alam Shama , Zhu Xuan , Madson Gabriel , Squiers Linda , Helmueller Leah , Southwell Brian , Gates Carlye , Kneedler Bonny , Limburg Paul J. , Finney Rutten Lila J.
Published: June 2023

e22514

Background: Several colorectal cancer (CRC) screening tests, shown to reduce CRC incidence and mortality, are recommended for average-risk adults aged 45-75 years. CRC screening is underutilized in the US with access to facility-based options, such as colonoscopy, representing a barrier to screening. Stool-based tests are guideline-endorsed and offer patients a convenient and more accessible CRC screening option that can be completed at home. Provider recommendation is consistently identified as the primary factor driving patient adherence. Understanding how aspects of patient-provider communication influence CRC screening can inform interventions to improve adherence. We developed a survey, informed by behavioral theory, to identify communication factors associated with completion of mt-sDNA screening. Methods: Adults aged 45-75 years, with a US postal address, who received a valid order for mt-sDNA and whose kit was shipped between 5/21-9/21 were eligible for sampling. The survey was administered by RTI International between 3/22-6/22. Participants could complete electronic or paper surveys. We fit a multivariable logistic regression to identify patient-provider communication factors associated with mt-sDNA test completion. Results: 2,973 respondents completed the survey (response rate = 21.7%). The majority (77.3%) completed the mt-sDNA test and said they would be ‘very likely’ (76.8%) to complete Cologuard in the future. The proportion of respondents who had conversations with their healthcare provider about Cologuard, and the specific content of those conversations, was significantly different between completers and non-completers and between respondents who said they were ‘very likely’ to complete Cologuard in the future compared to respondents who were not. Results from a binary logistic regression suggested that discussions with a healthcare provider related to step-by-step instructions for completing Cologuard (OR = 1.62) and needing to have a colonoscopy follow-up (OR = 1.93), as well as feeling included ‘a great deal’ in the decision-process with respondents’ healthcare provider (compared to ‘somewhat’ or ‘not at all’) increase the odds of kit completion. Additionally, healthcare provider discussions relating to test cost (OR = 1.47) and performance (OR = 1.72), as well as feeling included ‘a great deal’ in the decision-process was positively associated with respondents indicating they were ‘very likely’ to use Cologuard in the future. Provider discussions about the cost of a follow-up colonoscopy was negatively associated with a ‘very likely’ future user (OR = 0.52). Conclusions: Healthcare providers play a key role in patient adherence to CRC screening and must be appropriately prepared and resourced to educate and to engage patients in shared decision-making about CRC screening.
Barriers to breast cancer screening in a developing middle eastern country: A nationwide survey.
Authors: Abdulelah Zaid A. , Abdulelah Ahmed A. , AlQirem Lina , AlSamhori Jehad , Al-Qirem Ahmad , AlSamhori Abdel Rahman
Published: June 2023

e22517

Background: Breast cancer imposes a significant global health burden not only due to being constantly ranked as the leading malignancy in females, but also due to the immense resulting morbidity and mortality. Despite the presence of screening modalities, the uptake is relatively low due to unidentified barriers in many countries and regions. The Identification of these barriers towards screening is of paramount importance to tackle the health burden imposed by breast cancer, especially in countries like Jordan, a developing middle eastern country. Methods: A self-reporting survey consisting of comprehensive questions regarding the participant’s demographics, medical history, knowledge about breast cancer and the screening modalities was distributed to females aged 25 years and above with no prior history of breast cancer who are residing across the different regions of Jordan. The first consecutive 790 participants were enrolled, and data analysis was performed to identify the key barriers. Results: The mean age of the enrolled study population was 41 ± 9 years old with the majority being married (82.8%), have underwent a higher level of education (86.5%), are non-smokers (75.2%), and are medically insured (72.4%). 209 participants (26.5%) had reported a family history of breast cancer, while 83.4% of the participants reported awareness about breast cancer screening modalities with breast self-examination being the most commonly known modality of screening in 39.2% of the participants. Only 22.4% of the participants were aware of the 3 available screening methods. The majority of the participants (57.1%) did not undergo previous screening. When the participants who did not undergo previous breast cancer screening were compared with those who did, the participants without prior screening were more likely to report the lack of knowledge towards screening modalities (27.7% vs 8.0%) (p-value < 0.001), fear of the results (22.6% vs 13.9%) (p-value = 0.002), fear of pain during or after from the test (10.4% vs 5.9%) (p-value = 0.024), and feeling of embarrassment provoked by the screening test (15.7% vs 6.5%) (p-value < 0.001) as key barriers. On the contrary, there was no statistically significant difference between the two groups when assessing financial aspect of screening uptake as a potential barrier (p-value = 0.860). Conclusions: Despite the considerably high percentage of participants being aware of breast cancer screening modalities, an alarmingly low rate of screening uptake was witnessed due to several barriers. The collective identification of lack of knowledge towards screening modalities and the nature of the available tests, in addition to the fear of the results and pain following the test, and feeling of embarrassment undoubtedly mandates the formulation of comprehensive awareness campaigns that effectively tackle these barriers.
A case-control study of 10,757 individuals to assess potentially modifiable risk factors, including stress, for breast cancer among Chinese patients in Hong Kong.
Authors: Yeo Winnie , Yuen Lok-Wa , Tsoi Kelvin Kf , Chan Emily YY , Kwok Carol , Soong Sung Inda , Ng Ting Y. , Chiu Joanne , Chan Miranda , Chan Sharon Wing Wai , Wong Ting T. , Chan Yolanda HY , Li Lawrence PK , Yau Chun C , Hung Wai K. , Cheung Polly Suk-yee
Published: June 2023

e22522

Background: Breast cancer is the most common cancer in women worldwide. Both intrinsic and environmental factors contribute to the disparities in breast cancer incidence across different regions. In Hong Kong, the incidence has been increasing in the past decades. With over 4700 women diagnosed in 2019, breast cancer is responsible for 27% of all female cancers in Hong Kong. Apart from intrinsic non-modifiable risk factors, some risk factors are modifiable and may reduce cancer risk. Methods: We conducted a case-control study that involved breast cancer patients from the Hong Kong Breast Cancer Registry with matched healthy controls from the community between 2014 and 2017. A standardized written questionnaire was used through face-to-face interviews of all study participants. The questionnaire collected information on participants’ demographics, general health, smoking history and other lifestyle factors including physical activity, self-assessed dietary habits (balanced, vegetarian, meat and dairy-rich diets), self-perceived stress levels (measured with a 4-point Likert scale, and high stress level was defined as having over 50% of the participant’s time with stress being scored 3 or above out of a Likert scale of 4), body mass index, family history, menstrual and reproductive history, and history on the use of oral contraceptives and hormone replacement therapy. Multiple logistic regression was fitted to compare all risk factors. Results: A total of 5,186 breast cancer patients and 5,571 controls were recruited. Modifiable risk factors that were shown to be associated with an increased risk of breast cancer included self-perceived high stress level (adjusted odd ratios [aOR] = 3.44; 95% CI = 3.13-3.78), meat-rich diet (aOR = 1.77; 95% CI = 1.54-2.04), dairy-rich diet (aOR = 3.33; 95% CI = 2.01-5.52), overweight/obese status (aOR = 1.21; 95% CI = 1.10-1.32), delayed child-bearing (aOR = 2.23; 95% CI = 1.79-2.79), nulliparity (aOR = 1.21; 95% CI = 1.08-1.35) and ever use of oral contraceptives (aOR = 1.34; 95% CI = 1.22-1.47), while exercise (OR = 0.62; 95% CI = 0.56-0.68) and breast-feeding (aOR = 0.76; 95% CI = 0.69-0.83) were associated with reduced risk. Conclusions: In Hong Kong, high stress level, meat- and dairy- rich diet, overweight/obese, reproductive history and use of oral contraceptives were identified to be modifiable risk factors for breast cancer. Adjusting these factors through lifestyle modification may curb the increasing trend of breast cancer incidences in the coming decades.
Opinions and usage of cancer-associated thrombosis scoring systems among hematologists and oncologists: An international survey.
Authors: Agrawal Amulya , Bat Taha , Ibrahim Ibrahim , Choi Sung-Hee , Khan Adeel
Published: June 2023

e22531

Background: Cancer-associated thrombosis (CAT) occurs in 20% of cancer patients and is currently their second leading cause of death. Several scoring systems (i.e., Khorana Risk Score, COMPASS-CAT, Vienna-CATS, etc) have been developed to allow clinicians to determine CAT risk and prescribe appropriate treatments. There is little data about how hematologists and oncologists use these risk assessment models in daily practice. We conducted a survey of hematologists and oncologists in different institutions about their usage and opinions of CAT scoring systems. Methods: We created a twelve-question survey querying hematologists and oncologists regarding their usage and perspectives on CAT and scoring systems. Survey participation was voluntary, non-incentivized, and anonymous. The survey was advertised on social media and email list groups from January to February 2023. Descriptive statistics were analyzed in R version 4.1.2. Results: Seventy hematologists/oncologists responded with 88.4% from the US and 11.6% international. The plurality of respondents (35.7%) identified as sub-specialty oncologists (e.g., GI oncology, thoracic oncology, etc), 18.6% identified as malignant hematologists, and 15.7% identified as non-malignant hematologists. Overall 71.4% of respondents worked in academic settings. The majority (57.1%) stated they do not use any CAT scoring system and 15.7% stated they do not have familiarity with any CAT scoring system. Zero respondents strongly agreed that they often use scoring systems. Of the CAT systems used, the Khorana score was by far the most common (80.0%). Respondents somewhat agreed (14.3), somewhat disagreed (10%), or were undecided (34.3%) that scoring systems make it easier to determine CAT risk in practice. The majority (54.3%) were also undecided that these systems’ predictions of CAT risk are accurate. There was general agreement in worry of bleeding in anticoagulating cancer patients prophylactically (strongly agree 12.9%, agree 32.9%, somewhat agree 22.9%). Respondents strongly agreed (34.3%) or agreed (40.0%) that decisions about anticoagulation are important part in cancer patients’ supportive care. Similarly, respondents strongly agreed (30.0%), agreed (38.6%), or somewhat agreed (22.9%) that counseling patients on CAT is important. Conclusions: To our knowledge, this is the first survey assessment of hematologists and oncologists regarding their opions on CAT and their usage patterns of scoring systems. Despite the widespread agreement that counseling regarding CAT is important and that decisions about anticoagulation are a vital part of a cancer patient's supportive care, most clinicians do not use CAT scoring systems in practice or are not familiar with them. Hematologists and oncologists worry about the risk of bleeding with anticoagulation and agree there is a need for new and improved CAT scoring systems.
Time trend on breast cancer mortality: How are we allocating physicians to deal with the disease in men and women in Brazil?
Authors: Schoueri Jean Henri , Werneck De Carvalho Luis Eduardo , Sette Claudia Vaz De Melo , de Abreu Luiz Carlos , Fonseca Fernando Luiz Affonso , da Silva Paiva Laercio , Adami Fernando
Published: June 2023

e22532

Background: Female breast cancer (FBC) is a well-known public health issue worldwide. However, male breast cancer (MBC) is a rare condition, which might be overlooked by public health authorities and clinicians alike. Methods: Ecological study conducted with secondary data from 2008-2020 to examine the relationship between the amount of doctors per inhabitant on FBC and MBC mortality in Brazil and its federative regions. All data were gathered from Brazil’s public health system. For each cancer, mortality was analyzed by age and standardized by the World Health Organization’s population. The number of physicians was obtained from the Unified Health System and was calculated as the rate per 100,000 inhabitants. Linear regression was performed using stepwise selection/backward elimination. Results: Despite not reaching statistical significance, the total amount of physicians that work in the Unified Health System (UHS) was positively associated with MBC mortality (β 0.00003, IC95% -5,77 x 10-6; 0.00007, p = 0.097), whereas there was a clear trend on FBC mortality reduction over the years (β -0.157, IC95% -0.2355;, p < 0.001) and with higher number of gynecologists (β -0.0400, IC95% -0.577; -0.2236, p < 0.001). Also, FBC mortality rates were positively associated with higher availability of physicians in general (β 0.0088, IC95% 0.0079; 0.0098, p < 0.001) in the UHS. Conclusions: Trends on FBC and MBC mortality rates differ in Brazil. Whereas higher mortality was associated with a greater amount of doctors per inhabitant, perhaps due to more diagnosis, trends on lower mortality rates were found only for FBC – in those cases, it was associated with more gynecologists available. For both neoplasms, there was no association between mortality rates and the amount of clinical oncologists nor primary care physicians available in the country. [Table: see text]
Measuring real-world concordance with evidence-based guidelines for genetic testing in patients with breast cancer: A retrospective quality review.
Authors: Ezratty Charlotte , Kessler Alaina J. , Klein Paula
Published: June 2023

e22542

Background: Genetic testing plays an important role in the detection and management of breast cancer. Patients with high-risk mutations may undergo more frequent screening and possible risk reduction with medical and surgical management. Genetic testing also guides treatment decisions, including the recent approval of adjuvant olaparib for patients with high-risk BRCA1/2-mutated early-stage breast cancer. The most recent NCCN guidelines expand the age recommendation for genetic testing for patients with a personal history of breast cancer from age ≤ 45 years to ≤ 50 years though in clinical practice, it is likely patients age 46-50 were undergoing genetic testing prior to this recommendation. The goal of this quality review was to assess real-world concordance with genetic testing as per NCCN guidelines and evaluate practice patterns of genetic testing in patients age 46-50 at two large academic centers with a diverse patient population. Methods: We conducted a retrospective quality review of patients age ≤ 50 years diagnosed with early-stage breast cancer at two academic centers from 2019 to 2021. Imaging, pathology, and genetic testing were abstracted from medical records. Baseline characteristics included age, gender, race, ethnicity, stage at diagnosis, receptor status, and genetic testing data. We used descriptive statistics to describe the population and genetic testing results. Results: There were a total of 376 patients with an average age of 44 years. Of these patients, 374 (99%) were female, 158 (42%) white, 76 (20%) African American, 60 (16%) Asian, and 77 (20%) identified as Hispanic. There were 255 patients (68%) diagnosed with stage I cancer, 82 (22%) with stage II, and 39 (10%) with stage III. There were 261 patients (69%) with hormone-receptor positive, HER2-negative cancer and 45 patients (12%) with triple-negative breast cancer (TNBC). Of the 230 patients age ≤ 45, 225 (98%) completed genetic testing. Of the patients who did not undergo genetic testing, 2 were offered and declined. Genetic mutations were found in 25 patients including 13 patients with BRCA1 and 4 patients with BRCA2. Of the 146 patients age 46-50, 134 (92%) completed genetic testing. Excluding patients with TNBC as genetic testing is recommended at any age for patients with TNBC, 115 patients (91%) underwent genetic testing. Mutations were identified in 8 patients including 3 patients with BRCA1 and 2 patients with BRCA2. Conclusions: Genetic testing is a key component of the pre-treatment diagnostic evaluation for patients with breast cancer given implications for management. Our study demonstrated nearly all patients age ≤ 45 with early-stage breast cancer underwent genetic testing, reflecting concordance with evidence-based guidelines. Furthermore, most patients age 46-50 at our institution had undergone genetic testing prior to the expanded NCCN guidelines.
BRCA mutations in triple negative breast cancer patients in Guatemala: A descriptive study.
Authors: Kihn-Alarcón Alba , Marroquin Flores Diana Beatriz , de Falla Vicky , Siliézar Mauricio , Silva Carlos , Velarde Angel
Published: June 2023

e22543

Background: In Guatemala, breast cancer is the most common malignancy among women, the habitants in the country are characterized by being of different ethnic groups and little is understood about the prevalence of germline mutations and their influence in the prognosis and diagnosis of triple negative breast cancer patients, reason why the aim of our study is to determine the prevalence of BRCA1 and BRCA2 germline mutations among this population. Methods: Forty-five patients with confirmed biopsy of triple negative breast cancer by immunohistochemistry treated at Liga Nacional Contra el Cáncer-INCAN Guatemala in 2022 were enrolled in the study. Triple negativity was defined as < 1% estrogen, progesterone and HER2 staining by immunohistochemistry or not amplified by fluorescence in situ hybridization in those with HER2 borderline result. After consent, patients had next generation sequencing and multiplex ligation-dependent probe amplification for BRCA1 and BRCA2 genes. From medical records, we obtained: demographic, clinico-pathological and treatment data. Median was calculated for age, while frequencies and percentages were computed for the categorical variables. Results: The study identified 19 patients with a BRCA1 or BRCA2 germline mutations (42.22%). The median age at cancer diagnosis was 39 vs. 49 years old compared to patients with lack of mutations of the genes analyzed. The majority harboring a mutation (36.84%) were from the countryside, especially the regions IV and V (southeast and central). Among all groups, (66.67%) were diagnosed with locally advanced disease and initially treated with neoadjuvant chemotherapy. According to our findings, the most prevalent mutations were located in the BRCA1 gene (47.37%), with BRCA1 c.212+1G > A and BRCA2 c.2806_2809del being the most frequent variants (36.84%). Conclusions: Triple negative breast cancer patients in Guatemala have higher prevalence of BRCA1 and BRCA2 mutations than reported among other populations, longer follow up of this study is expected to confirm the results and further understand how the presence of mutations could affect the response to treatment of the patients, their prognosis and the impact in their families. [Table: see text]
Breast cancer in patients with Lynch syndrome: A single institution retrospective analysis.
Authors: Miano Salvatora tindara , Petrioli Roberto , Martellucci Ignazio , Montagnani Francesco , Civitelli Serenella , Francini Guido , Giuffrida Dario , Mencarelli Maria Antonietta , Renieri Alessandra , Prestifilippo Angela , Francini Edoardo
Published: June 2023

e22549

Background: Lynch syndrome (LS) is associated with an increased risk of several malignancies including gastrointestinal, genitourinary, gynecologic, skin, and brain cancers. However, whether patients with LS have higher risk of developing breast cancer (BC) or not is still controversial and a relevant clinical question. Methods: From the Santa Maria alle Scotte Hospital registry, we retrospectively identified consecutive patients with LS diagnosed by detecting a germline heterozygous pathogenic or likely-pathogenic variant in MLH1, MSH2, MSH6 or PMS2 on molecular genetic testing within April 2016-January 2022. We compared our sample size to Surveillance, Epidemiology, and End Results Program (SEER) of 2017 National Cancer Institute database. Results: Overall, 43 patients with LS were identified. Of those, 11 (25.6%; 95% CI 1.58-26.72%; p < 0.0001) had histologically confirmed BC, 10 (91%) of whom were hormone receptor positive tumors and BC is the only diagnosis of cancer to date. In this 11 patients median age at diagnosis was 54.5 years. 45% of 11 BC LS patients has germinal MSH2 mutation , 45% of 11% are MSH6 mutaded and has a more aggressive breast cancer. Median follow-up was 3 years and 8 months. All patients are still alive and under treatment. Conclusions: Within the limitations of a small sample size and retrospective design, our analysis suggests a significant association between patients with LS and the diagnosis of primary BC. Validation of such findings through prospective clinical studies with larger samples is warranted and would lead to fundamental modifications to LS screening and follow-up international recommendations.