Breast Lymphoma Research Articles

Primary breast lymphoma in males: Incidence, demographics, prognostic factors, survival, and comparisons with females.

BackgroundPrimary breast lymphoma (PBL) is a rare disease condition and is mainly observed in females. No male PBL cohorts were reported previously. This study aims to investigate the incidence, clinical characteristics, prognostic factors, and survival outcomes among male PBL patients and also to perform comparisons between males and females.MethodsPatients diagnosed with PBL between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database were identified. Age-adjusted incidence rates were calculated by year and age for trend analysis. Univariate and multivariate Cox hazard proportional regression analyses were performed to identify prognostic factors. Survival comparisons were conducted using the Kaplan–Meier method and the log-rank test. The propensity matching score (PSM) method was used to balance demographics.ResultsThe incidence rate of 122 male PBL patients diagnosed in the period of 2000 to 2019 was 0.169 (95% CI: 0.140–2.203) per million persons, which was much lower than that of 2,543 females (1.59, 95% CI: 1.53–1.65). Clinical demographics were similar between females and males, except for lymphoma subtype distribution (P = 0.025). A higher age [hazard ratio (HR) = 1.08, 95% CI: 1.05–1.12, P < 0.001] and not receiving radiotherapy (receiving vs. not receiving: HR = 0.41, 95% CI: 0.21–0.78, P = 0.007) were significant risk factors associated with overall survival (OS) in males. Radiotherapy (OS: P = 0.023) can offer benefits in OS. Using the PSM method, we also revealed that male PBL patients had significantly worse OS and cancer-specific survival rates than females.ConclusionsThis study first analyzed male patients with PBL involving incidence, clinical characteristics, and survival data. Sex disparity was also observed in the survival outcome of the disease.

Statins and Left Ventricular Ejection Fraction Following Doxorubicin Treatment

BackgroundStatins taken for cardiovascular indications by patients with breast cancer and lymphoma during doxorubicin treatment may attenuate left ventricular ejection fraction (LVEF) decline, but the effect of statins on LVEF among patients with no cardiovascular indications is unknown.MethodsA double-blind, placebo-controlled, 24-month randomized trial of 40 mg of atorvastatin per day administered to patients with breast cancer and lymphoma receiving doxorubicin was conducted within the National Cancer Institute Community Oncology Research Program across 31 sites in the United States. At pretreatment and then 6 and 24 months after initiating doxorubicin, we assessed left ventricular (LV) volumes, strain, mass, and LVEF through cardiac magnetic resonance imaging, along with cognitive function and serum markers of inflammation. The primary outcome was the difference in 24-month LVEF between placebo and treatment groups, adjusted for pretreatment LVEF.ResultsA total of 279 participants were enrolled in the trial. Participants had a mean (±SD) age of 49±12 years; 92% were women; and 83% were White. The mean (±SD) LVEF values were 61.7±5.5% before treatment and 57.4±6.8% at 24 months in the placebo group and 62.6±6.4% before treatment and 57.7±5.6% at 24 months in the atorvastatin group. On the basis of a multiple imputed data set for missing data and adjusted for each individual’s pretreatment LVEF, 24-month declines in LVEF averaged 3.3±0.6 percentage points and 3.2±0.7 percentage points, for those randomly assigned to placebo versus statins, respectively (P=0.93). Across both treatment arms, similar percentages of individuals experienced changes of more than 10 percentage points in LVEF, LV strain, LV mass, cognition, and inflammation biomarkers, including among those with greater than 90% drug compliance.ConclusionsIn patients with breast cancer and lymphoma with no existing indication for statin therapy, prospective statin administration did not affect LVEF declines 2 years after doxorubicin. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01988571.)

Anaplastic large cell lymphoma of breast masquerading suppurative mastitis on cytology

Breast is an uncommon site of extra nodal lymphoma accounting for 2.2% of all extra nodal lymphomas. B cell lymphomas are more common than T cell types. The most common subtype is Diffuse Large B Cell Lymphoma. Breast lymphoma is very challenging to diagnose as it has nonspecific clinical and radiological features. We report a rare case of primary T cell lymphoma in a 20-year-old female. It was misdiagnosed as abscess on ultrasound and as suppurative mastitis on fine needle aspiration cytology (FNAC). However, excisional biopsy was suggestive of lymphoma and immunohistochemistry confirmed it as ALK positive, anaplastic large cell lymphoma. Even though FNAC is a part of the diagnostic triad for breast lesions, potential pitfalls cannot be overlooked and must be correlated with biopsy.

Genomic Mutation Landscape of Primary Breast Lymphoma: Next-Generation Sequencing Analysis.

Primary breast lymphoma (PBL) is a rare subtype of non-Hodgkin's lymphoma (NHL) with rapid progression and high risk of central nervous system metastasis. We have investigated 40 PBL patients retrospectively, and 16 of them were sequenced by a target panel of 112 genes related with lymphoma. Next-generation sequencing (NGS) identified 203 mutations spanning 35 genes and revealed seven potential protein-changing genes (PIM1, MYD88, DTX1, CD79B, KMT2D, TNFAIP3, and ITPKB) with high frequency, referring crucial roles in lymphomagenesis. Our result suggested that PIM1 mutation is correlated with the age and pathological type of PBL patients. Gene TNFAIP3 and KMT2D mutation is only related to the pathological type and primary site, respectively. These high-mutant genes detected in PBL indicated a tendency to shorten overall survival (OS) and progression-free survival (PFS), which may lead to poor prognosis. Furthermore, the nuclear factor kappa-B (NF-κB) pathway and related regulatory factors are essential for the development of targeted therapy as well.

Cancers Among Adolescents and Young Adults in Maine 2001-2017: A Descriptive Analysis and Model for Future Studies.

Purpose: Maine has had a high age-adjusted incidence rate of cancer and a high incidence rate of childhood cancer. However, it is unknown if Maine adolescents and young adults (AYAs) have a higher-than-expected cancer incidence rate. Methods: Based on the International Classification of Diseases of Oncology, Third Edition (ICD-0-3) classification system, we obtained the incidence rates of AYA cancers by state, sex, race, and ethnicity from 2001 to 2017 using CDC WONDER. Overall, all cancer rates and age-adjusted incidence rates for specific cancers were compared and ranked by state. Results: Maine had a similar overall age-adjusted cancer incidence rate among non-Hispanic white AYAs compared with the national rate from 2001 to 2017. Among non-Hispanic white AYA cancers of the respiratory system, lung and bronchial cancers, uterine cancer, female breast cancer, thyroid cancer, lymphomas, and Hodgkin's lymphoma were significantly greater in Maine than the state with the lowest incidence rate for that cancer. Specifically, Maine was ranked as one of the top 10 states for the highest incidence rate of lung cancer, uterine cancer, Hodgkin's lymphoma, thyroid cancer (males only), and female breast cancer. Conclusion: Although the cancer incidence rate among AYAs in Maine was not significantly higher than the national average, Maine AYAs had a significantly higher incidence of lung cancer, uterine cancer, Hodgkin's lymphoma, thyroid cancer, and breast cancer. This information may direct future studies to identify regional cancer risk factors in Maine, which may account for this elevated rate. The described methodology is an innovative approach to identifying states with high cancer rates and directing future studies.

Impact of pectoralis muscle loss on cardiac outcome and survival in Cancer patients who received anthracycline based chemotherapy: retrospective study

IntroductionThe impact of pectoralis muscle mass index (PMI) on cardiac events is not well studied in cancer patients, especially in those who have received chemotherapy with high potential cardiac toxicity such as anthracyclines.MethodsIndividuals aged ≥18 years with a diagnosis of breast cancer, sarcoma, or lymphoma who received anthracycline-based chemotherapy at the University of Minnesota MHealth Fairview between 2009 and 2014. Eligible patients had to have two CT scans: a baseline CT scan within 6 months prior to chemotherapy and a follow-up CT scan within 2 years after treatment. The PMI was calculated as the right pectoralis muscle area indexed to height squared. Multivariable linear regression was used to analyze factors associated with PMI at follow-up, overall mortality, and major cardiac events (MACE).ResultsA total of 474 patients (breast cancer 192; lymphoma 184; sarcoma 98) participated with a median age of 61 years at the time of baseline CT scan; 161 (34%) were male. Almost all patients received anthracyclines except 12% who received trastuzumab only. The median baseline PMI was 5.8 cm2/m2 (4.9, 7.7) which decreased 10.5% after chemotherapy, to 5.2 cm2/m2 (4.4, 6.4). Baseline PMI was not significantly associated with OS, but we detected lower risks of MACE with larger PMI at baseline. Greater baseline PMI was associated with greater follow-up PMI, but also with greater relative PMI loss. Female gender, older age, and history of smoking were also associated with greater PMI losses.ConclusionGreater pre-treatment pectoralis muscle index in patients treated with anthracyclines have a lower risk of MACE. Early identification of sarcopenia using PMI could trigger proactive engagement for intervention and risk-stratified therapies.

Breast lymphomas, breast implants and capsules The timeline of BIA-ALCL with respect to surgical consent: the UK perspective

Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) is a rare type of T-Cell (non-Hodgkin's) lymphoma associated with the use of silicone breast implants. Recent widespread awareness has focused not only on the management of this condition but also in regards to potential litigation of surgeons, clinics, and breast implant manufacturers. Allegations of causation and inappropriate patient consent are being raised. The purpose of this article is to establish the timeline of relevant discoveries regarding this condition and associated implications with regards to appropriate informed patient consent.

Evaluating the safety and effectiveness of PegaGen® (pegfilgrastim) for the prevention of chemotherapy-induced febrile neutropenia: a post-marketing surveillance study.

Phase IV clinical trials are required to evaluate the real-world safety and effectiveness of drugs. This study aimed to evaluate the safety and effectiveness of once-per-cycle administration of PegaGen® (pegfilgrastim, CinnaGen, Iran) in cancer patients. In this open-label, multicenter, prospective, real-world, post-marketing surveillance study, patients with any type of cancer receiving chemotherapy regimens with a high risk of febrile neutropenia (FN) were included if they were prescribed pegfilgrastim for FN prophylaxis. The primary objective of this study was to assess the safety and the secondary objective was to assess the effectiveness of pegfilgrastim in the prevention of FN in cancer patients. A total of 654 patients (51.73 ± 15.12years of age) were enrolled and 3615 cycles of pegfilgrastim injections were recorded. The most common malignancies among the study patients were breast cancer (n = 192, 29.36%), lymphoma (n = 131, 20.03%), and gastric cancer (n = 65, 9.94%). The median (Q1, Q3) number of pegfilgrastim cycles per patient was 6 (4, 7). A single 6mg dose was injected in 99.17% of the cycles. A total number of 816 adverse events (AEs) were reported in 246 patients (37.62%). Bone pain was recorded in 141 patients (21.56%) and in 440 cycles (12.17%). Among all patients, 45 patients (6.88%) experienced FN 51 times, and FN frequency was 1.4% among cycles. Moreover, 14 (2.14%) patients were hospitalized following FN. Antibiotics were administered to 24 patients (3.67%) for FN treatment. The results from this post-marketing surveillance study support the safety and effectiveness of PegaGen® used for the prevention of chemotherapy-induced FN in patients with various types of cancer and treatment regimens. Clinicaltrials.gov identifier: NCT04460079.

Patterns of treatment and their outcomes in primary breast lymphoma; a comprehensive population-based analysis.

Primary breast lymphoma (PBL) is managed differently among centers, using surgery, systemic therapy and/or radiation. With data derived from the National Cancer Database (NCDB), we aim to describe treatments utilized in the United States, estimate the overall survival (OS) of different therapeutic modalities and determine the role of systemic therapy in patients with PBL. We conducted a retrospective cohort study using de-identified data from the NCDB. The NCDB provided records of 4616 patients diagnosed with PBL between 2004and 2015. We excluded patients diagnosed with HIV, with no survival data, not treated in the reporting facility, without histologic confirmation, with stage III/ IV disease and for whom surgery, radiation, or systemic therapy was contraindicated. Both propensity score weighting and Cox models were used to obtain adjusted estimates. Based on histopathology, PBL was classified into indolent (I-PBL) and aggressive (A-PBL). In a sample size of 2063 PBL patients, the median age was 67years (interquartile range (IQR): 57-78), and 97% were females. In 1027 patients with I-PBL, the median follow-up was 66months (95% confidence interval (CI): 32.6-107.2) and 60% of patients had extranodal marginal zone subtype. Systemic therapy did not improve adjusted-OS (median: 154 vs. 143months, P = 0.36) (Hazard ratio (HR): 0.86, 95% CI: 0.60-1.25, P = 0.42). The treatment arms associated with the highest adjusted 5-year OS were as follows: radiation (85%), surgery (79%), systemic & radiation (87%) and radiation & surgery (87%) (P = 0.9). In 1036 patients with A-PBL, the median follow-up was 67.4months (95% CI: 35.9-105), and 87% of patients had diffuse large B-cell subtype. Patients with A-PBL who received systemic therapy had an improved adjusted-OS (median: 115 vs. 72months, P < 0.01) (HR: 0.45, 95% CI: 0.38-0.53, P < 0.001). The treatment arms associated with the highest adjusted 5-year OS were: systemic (69%), systemic & radiation (77%), systemic & radiation & surgery (79%) and systemic & surgery (79%) (P = 0.4). Systemic therapy used as first-line treatment is essential in A-PBL. Local therapy in the I-PBL using surgery and/or radiation is effective in long-term disease control. There is significant variation in front-line treatment modalities utilized in PBL across the US, many associated with similar outcomes.

Rationale and Design of the Cardiac CARE Trial: A Randomized Trial of Troponin-Guided Neurohormonal Blockade for the Prevention of Anthracycline Cardiotoxicity.

Anthracyclines are effective cytotoxic drugs used in the treatment of breast cancer and lymphoma but are associated with myocardial injury, left ventricular dysfunction, and heart failure. Anthracycline-induced cardiotoxicity is highly variable in severity and without a proven therapeutic intervention. β-Adrenergic receptor blockers and renin-angiotensin-system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients. The Cardiac CARE trial is a multicentre prospective randomized open-label blinded end point trial of combination β-adrenergic receptor blocker and renin-angiotensin-system inhibitor therapy in patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy that is associated with myocardial injury. Patients at higher risk of cardiotoxicity with plasma high-sensitivity cTnI (cardiac troponin I) concentrations in the upper tertile at the end of chemotherapy are randomized to standard of care plus combination candesartan and carvedilol therapy or standard of care alone. All patients undergo cardiac magnetic resonance imaging before and 6 months after anthracycline treatment. The primary end point is the change in left ventricular ejection fraction at 6 months after chemotherapy. In low-risk nonrandomized patients, left ventricular ejection fraction before and 6 months after anthracycline will be compared with define the specificity of the high-sensitivity cTnI assay for identifying low-risk participants who do not develop left ventricular systolic dysfunction. Cardiac CARE will examine whether cardiac biomarker monitoring identifies patients at risk of left ventricular dysfunction following anthracycline chemotherapy and whether troponin-guided treatment with combination candesartan and carvedilol therapy prevents the development of left ventricular dysfunction in these high-risk patients.

Mysterious Case of Reduction in HDL Cholesterol in a Patient with B-cell Monocytosis

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> We review a clinical scenario involving a 66-year-old male seen in clinic for acute change in clinical status. This is intended to highlight reduction in HDL levels associated with progressive anemia, thrombocytopenia, and splenomegaly suspicious for B-cell predominant lymphoma. <h3>Objective/Purpose</h3> To review the relationship of HDL cholesterol levels and inflammatory states suspected for lymphoma and its impact on clinical management. <h3>Methods</h3> In addition to close follow-up at primary care clinic, he was referred to hematology for further evaluation for workup such as bone marrow biopsy. <h3>Results</h3> A 66-year-old male with history of hypothyroidism, chronic kidney disease, and dyslipidemia on statin was now found to have progressive worsening fatigue over weeks along with hematologic changes such as anemia, thrombocytopenia and splenomegaly. Initial referral to hematology for clinical change did not raise any concern due to grossly borderline hematologic laboratory values. However, importantly, patient was noted to have significant acute drop of ∼40% in HDL levels during this period. This finding along with a clinical change prompted further workup from hematology revealing atypical lymphocytes observed on peripheral smear with 43.6% CD19 positive B cells with CD5 and CD10 negative on flow cytometry as well as a bone marrow and lymph node biopsy. <h3>Conclusions</h3> Cholesterol plays an integral role in structural maintenance of cell membranes, intracellular and intercellular signaling, and metabolism. Several cohort studies have shown an inverse correlation between serum HDL cholesterol levels and malignancy such as breast cancer, lymphoma and leukemia, particularly non-hodgkin's lymphoma (NHL). Based on many epidemiologic and prospective studies, it has been hypothesized that chronic inflammation may result in reduction of HDL cholesterol and perhaps may act as a potential marker of severity of systemic inflammation and inflammation-induced NHL risk. Interestingly, HDL cholesterol seems to modulate inflammatory responses independent of non-HDL cholesterol levels by inhibiting cytokine-induced expression of endothelial cell adhesion molecules and by suppressing chemotactic activity of monocytes and lymphocytes. In our clinical case, our patient may not be adequately evaluated based on borderline hematological laboratory abnormalities. However, a drastic drop (∼40%) in HDL cholesterol levels along with a change in clinical status promptly acted as a marker for further evaluation of a concerning and potentially fatal inflammatory state.

Predicting miRNA-disease associations based on graph attention network with multi-source information

BackgroundThere is a growing body of evidence from biological experiments suggesting that microRNAs (miRNAs) play a significant regulatory role in both diverse cellular activities and pathological processes. Exploring miRNA-disease associations not only can decipher pathogenic mechanisms but also provide treatment solutions for diseases. As it is inefficient to identify undiscovered relationships between diseases and miRNAs using biotechnology, an explosion of computational methods have been advanced. However, the prediction accuracy of existing models is hampered by the sparsity of known association network and single-category feature, which is hard to model the complicated relationships between diseases and miRNAs.ResultsIn this study, we advance a new computational framework (GATMDA) to discover unknown miRNA-disease associations based on graph attention network with multi-source information, which effectively fuses linear and non-linear features. In our method, the linear features of diseases and miRNAs are constructed by disease-lncRNA correlation profiles and miRNA-lncRNA correlation profiles, respectively. Then, the graph attention network is employed to extract the non-linear features of diseases and miRNAs by aggregating information of each neighbor with different weights. Finally, the random forest algorithm is applied to infer the disease-miRNA correlation pairs through fusing linear and non-linear features of diseases and miRNAs. As a result, GATMDA achieves impressive performance: an average AUC of 0.9566 with five-fold cross validation, which is superior to other previous models. In addition, case studies conducted on breast cancer, colon cancer and lymphoma indicate that 50, 50 and 48 out of the top fifty prioritized candidates are verified by biological experiments.ConclusionsThe extensive experimental results justify the accuracy and utility of GATMDA and we could anticipate that it may regard as a utility tool for identifying unobserved disease-miRNA relationships.

Abstract 2639: KB-0742 is active in preclinical MYC high models of TNBC, ovarian, and DLBCL cancers

Abstract MYC is an early-response gene downstream of many receptor complexes, and a component that promotes several pro-growth signal transduction pathways. As a result, MYC expression is highly regulated, but once dysregulated in cancer, MYC promotes tumorigenesis via activation of cell growth, proliferation, and angiogenesis. CDK9 is both an upstream and downstream cofactor of MYC. CDK9 promotes MYC expression through its recruitment to super enhancers at the MYC amplicon and acts as a cofactor to drive gene expression programs. Previously, we profiled pan-cancer sensitivity to KB-0742, a potent, selective, and orally bioavailable small-molecule inhibitor of CDK9, and identified MYC-amplified cancers as being especially sensitive to KB-0742. To better understand the connection between MYC and KB-0742 sensitivity, 11 different tumor types were evaluated preclinically using immortalized cell lines, patient-derived cell lines (PDCs), patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). The 11 indications included head and neck, esophageal, gastric, liver, non-small cell lung cancer (NSCLC), pancreatic, ovarian, triple-negative breast cancer (TNBC), prostate, colon, and lymphoma. For 5 of the indications (head and neck, esophageal, gastric, liver, and colon), little activity was observed in cell lines and in vivo with weak correlations to MYC amplification. TNBC, ovarian cancer, and lymphoma showed good responses to KB-0742 treatment. For TNBC and ovarian, immortalized and patient-derived cell lines indicated lower IC50 values with increased MYC amplification or expression, but the results were not statistically significant. However, in vivo assessments using 15 PDX models showed good correlation of tumor growth inhibition (TGI) and MYC amplification/expression, with some tumor regressions observed in several ovarian models. Two PDO models of TNBC with different treatment histories were also treated with KB-0742 and compared to 4 standard-of-care (SOC) compounds. KB-0742 showed much greater activity in the models, with maximal inhibition rates of 100% and 89%. Cell-line screens of blood cancer-derived cell lines showed that lymphocyte-derived cell lines were the most sensitive to KB-0742 as compared to all other cancer types. We tested several PDX models for response to our compound. Treatment with KB-0742 resulted in TGIs of over 50% in several lymphoma models, including a TGI of 56% in 1 model of double-hit diffuse large B-cell lymphoma. These data support the continual development of KB-0742, which is currently being tested in a phase 1/2 clinical trial (NCT04718675). The dose-escalation phase is opened to relapsed or refractory solid tumors or non-Hodgkin lymphoma. Once a recommend phase 2 dose is determined, we plan to open dedicated expansion arms enrolling patients with MYC over-expression/amplification within the tumor types supported by these studies. Citation Format: Melinda A. Day, Douglas C. Saffran, Tressa Hood, Nikolaus Obholzer, Akanksha Pandey, Charles Y. Lin, Pavan Kumar, Jorge DiMartino. KB-0742 is active in preclinical MYC high models of TNBC, ovarian, and DLBCL cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2639.

Poor Prognosis of Diffuse Large B-Cell Lymphoma of the Breast: The Role of Dose-Dense Chemotherapy

Background: The aim of the study was to define if the use of an intensive regimen (dose-dense) of chemotherapy may improve response rate and outcome in patients with primary breast lymphoma (PBL), whose is considered as lymphoma presentation with an worse prognosis. Methods: Patients with pathological confirmed diagnosis of diffuse large B-cell lymphoma with clinical presentation on breast (PBL) , &gt; 18 years old, stage I and II, negative for immunodeficient syndrome, hepatitis A and B, previously untreated , with non-germinal center cell, were included in a open label clinical trial, phase II, were allocated to received an dose dense regimen of CHOP (cyclophosphamide , doxorubicine, vincristine and prednisone) Results: Between July 2006 to December 2016, seventy eight patients were enrolled in the study. Complete response was achieved in 76 (94.4%), patients. Five patients relapse , thus progression free survival at 5 years was 94.0% (95 % Confidence interval (CI): 87% to 98%%): three patients achieved a second response and are alive, overall survival at 5-years was : 95.3 (96%CI: 89% to 102%).Relapse at central nervous system has not been observed. Severe granulocytopenia was observed in 42.8 (93.0%) cycles, but no death associated to treatment were observed. Conclusion: The use a dose-dense regimen of chemotherapy improve outcome in this setting of patients; although severe acute toxicities were frequent , it well controlled. Relapse in central nervous system has not been observed. Thus, we considered that dose-dense chemotherapy will be employed in this setting of patients.

Machine learning models for accurate pretreatment prediction of chemotherapy associated LV dysfunction in patients with breast cancer and lymphoma receiving chemotherapy (WF-98213 PREVENT and CCCWFU9912 DETECT IV).

1553 Background: Cancer survivors receiving potentially cardiotoxic chemotherapy are at increased risk for developing left ventricular (LV) dysfunction. We implemented machine learning (ML) models to predict future LV dysfunction in patients with breast cancer or lymphoma scheduled to receive potentially cardiotoxic chemotherapy. Methods: We utilized prospectively collected data from NIH studies R01HL118740 (supported by the Wake Forest NCORP Research Base (UG1CA189824)) and R01CA167821. Data included measurements of LV function and demographic factors before, during, and 24 months after initiating potentially cardiotoxic chemotherapy. The two datasets were used both separately and collectively in the development of multiple ML models including penalized linear regression, support vector machine, and random forest (RF). A data preprocessing step properly handled missing information, data imbalance, and encoding. Hyperparameter tuning was performed using cross validation of training data. The final models were assessed with a 20% hold-out test dataset. Cardiotoxicity was defined as a pre- to 24-month post cancer treatment decline in LV ejection fraction (LVEF) of &gt; 10% or to an absolute value of &lt; 50%. Results: 276 patients were included in ML models (7% men, 93% women; age 52±13 years). The RF model based on the combined dataset had the best performance with a prediction accuracy, sensitivity, and specificity of 0.94, 0.81, and 0.98, respectively. The most important variables assessed pre-treatment as measured by the Gini impurity factor were in descending order, LVEF, global LV circumferential strain, LV end-systolic volume, body mass index, LV stroke volume, LV end-diastolic volume, and LV mass. Conclusions: Prior to cancer treatment, supervised ML methods such as RF models predicted declines in LVEF of &gt; 10% and/or to absolute values below 50% would occur 24 months after initiating chemotherapy for breast cancer or lymphoma. With further improvement and validation using larger datasets, these models may play an important role in cardio-oncology care during and following cancer treatment.

Randomized trial of atorvastatin during and following receipt of doxorubicin for breast cancer and lymphoma (WF-98213).

12072 Background: Statins taken for cardiovascular (CV) indications by breast cancer (BC) and lymphoma survivors during doxorubicin (DOX) treatment may attenuate left ventricular ejection fraction (LVEF) decline, but statin impact among these survivors with no CV indications is unknown. Methods: In 279 patients from 31 cancer centers, we conducted a double blind, placebo-controlled, 24-month randomized trial of 40mg/day atorvastatin among those receiving DOX for BC or lymphoma. At pretreatment, six and 24 months after initiating DOX for BC or lymphoma, we assessed LV volumes, strain, mass, and LVEF (via cardiac magnetic resonance), cognitive function and serum markers of inflammation. Using a linear model adjusted for pretreatment measures, our primary analysis assessed change in LVEF over time by randomization group. Results: Participants were aged 49±12 years; 92% women, 83% white race. The mean pooled LVEF decline from pretreatment to 24 months was 62.2±6.0% to 57.6±6.3% (p &lt; 0.001). Adjusting for pretreatment LVEF, 24-month declines in LVEF averaged 3.5±0.5% and 3.3±0.5% respectively for placebo vs statins (p = 0.83). Both randomized groups were similar for: incidence of &gt; 10% change in LVEF, LV strain, LV mass, cognition and inflammation biomarkers, including among those &gt; 90% study drug compliant (p &gt; 0.05 for all). Conclusions: In BC and lymphoma survivors with no existing indication for statin therapy, prospective statin administration does not appear to impact LVEF declines two years after doxorubicin. Clinical trial information: NCT01988571. [Table: see text]

Evaluation of changes in lymph node size and metabolism by PET CT in patients with cancer who have been immunized against COVID 19: A Mexican study.

e13647 Background: The risk of developing COVID-19 in patients with cancer has increased, directly influenced by age and the magnitude of comorbidities. In this population, the estimated mortality is 10.9%. With this, the urgent need for patients with cancer to get vaccinated against SARS COV 2 has generated an international response. With the ongoing vaccination campaign, experts in nuclear medicine have observed an increment in lymph node uptake in PET CT with 18 FDG. Increased uptake in lymph nodes in patients with a neoplastic diagnosis on PET CT 18 FDG must be closely followed and well-studied to differentiate disease progression from an inflammatory, fleeting reaction. Methods: Amongst the inclusion criteria were patients over 18 years of age with solid tumors, including lymphomas, who were on active oncologic treatment with chemotherapy, immune therapy, radiotherapy or under surveillance between April 2021 and July 2021 who underwent a PET CT scan and had at least one dose of a COVID 19 vaccine, and a prior PET CT to the vaccine for comparison. Patients were excluded who showed evidence of progression or disease recurrence of the primary tumor. We evaluated lymph node size and metabolism measured by SUV max in the PET CT scan prior to being vaccinated and posterior to, as well as patients’ clinical characteristics. Results: A total of 92 patients who met inclusion criteria were included in the study. Amongst those, 54.3% were women, the median age was 68 years (27 - 95 years), the most common neoplastic diagnoses were breast cancer (19.6%), gastrointestinal tumors (17.4%), urothelial tumors (9.8%), lymphomas (9.8%) and ovarian cancer (8.7%). 52.2% of patients were under surveillance and 47.8% were under active treatment. 79% of patients had at least 2 vaccine doses. 59% had received Pfizer vaccines and the measurable adenopathies were axillary in 32.7% and mediastinal in 27%. The medium size of the measured lymph nodes prior to receiving the vaccine was 2.86 mm with an SUV max of 1.24, while after vaccination were 6.01 and 2.27 respectively. A Kruskal Wallis test was conducted to compare median results according to histopathologic reports, with no statistical difference. A Mann Whitney U test was conducted to compare breast cancer to other cancer histologies, where a statistical difference was found for SUV max, p = 0.003 and size with p = 0.033. Conclusions: This work details significant differences between lymph node size and SUV max in oncologic patients pre and post vaccination for COVID 19, showing a statistical difference in patients with breast cancer. This increment in lymph node uptake in patients with a neoplastic diagnosis PET CT 18 FDG must be closely followed and well-studied to differentiate disease progression from an inflammatory reaction.

Characteristics and outcomes of COVID-19 in adult cancer patients: Tertiary cancer center experience.

e13601 Background: The COVID-19 pandemic has led to deteriorated outcomes among immunocompromised patients, significantly impacting cancer patients. However, little is known about the impact of the COVID-19 pandemic on cancer patients in low and middle-income countries. Therefore, we sought to investigate the characteristics and clinical outcomes of cancer patients with COVID-19 treated at a single institution. Methods: A retrospective chart review was performed for cancer patients treated at King Hussein Cancer Center. Patients who were diagnosed with laboratory-confirmed SARS-CoV-2 infection by Real-time Polymerase chain reaction test between April 2020 and October 2020 were identified. Results: Overall, 327 COVID-19-infected cancer patients were included. At the time of COVID-19 diagnosis, the median age was 55 years (range, 18-87 years), 146 patients (45%) were males. The most common neoplasms were breast cancer (n = 90, 27.5%), gastrointestinal cancers (n = 60, 18.3%), and lymphoma (n = 36, 11%). The majority of patients had comorbidities (n = 200, 61%), of which hypertension and diabetes mellitus were the most common. Testing reason was presence of symptoms in 183 (56%) patients, previous exposure in 10 (3.1%), and before elective procedure in 142 (43.4%). 118 patients (56.5%) were hospitalized and 18 patients (5.5%) required admission to the intensive care unit (ICU). At the time of the last follow-up, 76% (n = 249) remained alive, and 24% (n = 78) died, among which death was considered to be COVID related in 41 (52.5% of deaths). Mortality was significantly increased in patients with comorbidities (29%, vs 15.7 %; p = 0.008), the use of cardiac medications (34.3% vs. 18.1%; p = 0.001), active cancer status vs. remission (28.2% vs 11.6% p = 0.002), receiving chemotherapy in the last four weeks (27.6% vs 16.4%, p = 0.028), and when testing reason was the presence of symptoms vs exposure and elective (37.7% vs. 10% and 7.7% p = &lt; 0.001) respectively. Chemotherapy was delayed in 109 (33.4%) patients and permanently discontinued in 57 (17.5%) patients. Among patients required hospitalization and needed ICU admission, mortality rates were 55.1% and 88.9% respectively. Conclusions: COVID-19 infection is associated with significant mortality and negatively affects treatment plans in cancer patients. A follow-up study will be needed to evaluate the effect of vaccination on the outcomes.

Disparities in NCI and nonprofit organization funding and effect on cancers with high incidence rates among Black patients and mortality rates.

1509 Background: National Cancer Institute (NCI) and nonprofit organization (NPO) funding is critical for research and advocacy, but may not be equitable across cancers or racial and ethnic groups. Methods: This study evaluated funding from the NCI and NPOs supporting lung, breast, colorectal, pancreatic, hepatobiliary, prostate, ovarian, cervical and endometrial cancers, leukemia, lymphoma and melanoma from 2015-2018. The primary objectives were to assess for disparities in NCI and NPO funding across different cancers compared to their incidence and mortality and their incidence rates across age, racial and ethnic groups. We also investigated if underfunding correlates with fewer clinical trials. Correlations between NCI and NPO funding for each cancer and its incidence, mortality and number of clinical trials were analyzed using scatter plots and Pearson correlation coefficients (PCCs). Results: Diseases with the largest combined NCI and NPO funding were breast cancer ($3.75 billion) and leukemia ($1.99 billion). Those with the least funding were endometrial ($94 million), cervical ($292 million), and hepatobiliary cancers ($348 million). Disease-specific funding correlated well with incidence, but correlated poorly with mortality (PCCs: 0.74, p = 0.006 and 0.30, p = 0.346, respectively). Breast cancer, leukemia and lymphoma were consistently well-funded, while colorectal, lung, hepatobiliary and uterine cancers were consistently underfunded. These data are summarized in the Table. NCI and NPO funding increased proportionately as incidence increased for White patients (PCC: 0.73, p = 0.007), Hispanic patients (PCC: 0.66, p = 0.02), Asian/Pacific Islanders (PCC: 0.77, p = 0.003) and Native Americans and Alaskans (PCC: 0.72, p = 0.008) while cancers with higher incidence in the Black population were underfunded (PCC: 0.52, p = 0.08). The amount of combined NCI and NPO funding for a particular cancer correlated strongly with the number of clinical trials for that disease (PCC: 0.91, p &lt; 0.0001). Conclusions: Many cancers with high incidence and mortality are underfunded, including those with higher incidence among Black patients. Underfunding strongly correlates with fewer clinical trials, which could impede future advances in underfunded cancers. [Table: see text]

A Comprehensive Model for Diagnosis of Primary Breast Lymphoma Differentiated From Breast Cancer and Prognosis Evaluation of Surgical Treatment.

BackgroundThe objective of this work was to discriminate between primary breast lymphoma (PBL) and breast cancer by systematically analyzing clinical characteristics, laboratory examination results, ultrasound features, and mammography findings to establish a diagnostic model for PBL and to analyze the influence of surgical treatment on the prognosis of PBL patients.MethodWe analyzed 20 PBL and 70 breast cancer patients treated during the same period by comparing several characteristics: clinical features, such as age, tumor position, and breast complaints; laboratory examination findings, such as the lactate dehydrogenase (LDH) level, and imaging features such as the maximum diameter, shape, margins, aspect ratio, and calcification of the mass and axillary lymph node involvement. A diagnostic model was then developed using logistic regression analysis. The impact of surgery on the prognosis of PBL patients was assessed through Kaplan–Meier survival analysis.ResultBreast cancer and PBL could be distinguished based on imaging features, including the maximum diameter, shape, margin, and calcification of the mass, and lymph node involvement (P < 0.05). There were no significant differences between PBL and breast cancer patients in terms of clinical features, or the LDH level. The area under the receiver operating characteristic curve was 0.821. The log-rank test showed that surgery had no significant influence on the prognosis of PBL patients.ConclusionUltrasound and mammography are the most useful methods for detecting malignant breast tumors. Compared with breast cancer tumors, breast lymphoma tumors are larger with a more regular shape and less calcification and are often accompanied by axillary lymph node involvement. Patients with a breast malignancy should not undergo surgical excision without an accurate diagnosis.