Breast Diffuse Large B-cell Lymphoma Research Articles

Predicting central nervous system relapse in primary breast diffuse large B-cell lymphoma using the stage-modified IPI score: A retrospective cohort study

ObjectiveThe existing Central Nervous System-International Prognostic Index (CNS-IPI) provides insufficient guidance for predicting central nervous system (CNS) relapse in individuals with primary breast diffuse large B-cell lymphoma (DLBCL). This retrospective cohort study sought to examine the potential of the stage-modified IPI in predicting CNS relapse within this specific patient population. Patients and methodsWe examined the baseline characteristics of 76 consecutive patients diagnosed with primary breast DLBCL, calculating the stage-modified IPI score for each individual. Utilizing a competing risk regression (CRR) model, we conducted both univariate and multivariate analyses to explore the relationship between potential prognostic factors and the occurrence of CNS relapse. ResultsIn our cohort, the rates of CNS disease at 2 and 5 years since the diagnosis of primary breast DLBCL are 3.9% and 7.8%, respectively. Among patients experiencing CNS relapse, 80% presented with a parenchymal brain mass. Individuals with a high stage-modified IPI score (1–3 points) had a significantly higher incidence of CNS relapse (p = 0.031), a shorter time from the initial diagnosis of primary breast DLBCL to the first CNS relapse (p = 0.010), as well as relapse at any site (p = 0.012), compared to those with a low score (0 points). Univariate analysis identified stage (Hazard Ratio (HR): 4.098, p = 0.024), stage-modified IPI score (HR: 11.582, p = 0.012), and radiation therapy (HR: 5.784, p = 0.026) as significant risk factors. In multivariate analysis, in addition to radiation therapy (HR: 7.258, p = 0.012), the stage-modified IPI score (1–3 points versus 0 points) emerged as an independent and reliable predictor for CNS relapse (HR: 12.945, p = 0.016). ConclusionOur study underscores the significance of stage-modified IPI scores in predicting CNS relapse for patients with primary breast DLBCL. Validation of these findings through further research is essential, along with exploring potential prevention and intervention approaches.

Comparative analysis of conventional ultrasound and shear wave elastography features in primary breast diffuse large B-cell lymphoma

Comparative analysis of conventional ultrasound and shear wave elastography features in primary breast diffuse large B-cell lymphoma

End-to-end deep learning radiomics: development and validation of a novel attention-based aggregate convolutional neural network to distinguish breast diffuse large B-cell lymphoma from breast invasive ductal carcinoma.

Apart from invasive pathological examination, there is no effective method to differentiate breast diffuse large B-cell lymphoma (DLBCL) from breast invasive ductal carcinoma (IDC). In this study, we aimed to develop and validate an effective deep learning radiomics model to discriminate between DLBCL and IDC. A total of 324 breast nodules from 236 patients with baseline 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) were retrospectively analyzed. After grouping breast DLBCL and breast IDC patients, external and internal datasets were divided according to the data collected by different centers. Preprocessing was then used to process the original PET/CT images and an attention-based aggregate convolutional neural network (AACNN) model was designed. The AACNN model was trained using patches of CT or PET tumor images and optimized with an improved loss function. The final ensemble predictive model was built using distance weight voting. Finally, the model performance was evaluated and statistically verified. A total of 249 breast nodules from Fudan University Shanghai Cancer Center (FUSCC) and 75 breast nodules from Shanghai Proton and Heavy Ion Center (SPHIC) were selected as internal and external datasets, respectively. On the internal testing, our method yielded an area under the curve (AUC), accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and harmonic mean of precision and sensitivity (F1) of 0.886, 83.0%, 80.9%, 85.0%, 84.8%, 81.2%, and 0.828, respectively. Meanwhile on the external testing, the results were 0.788, 71.6%, 61.4%, 84.7%, 84.0%, 62.6%, and 0.709, respectively. Our study outlines a deep learning radiomics method which can automatically, noninvasively, and accurately differentiate breast DLBCL from breast IDC, which will be more in line with the needs and strategies of precision medicine, individualized diagnosis, and treatment.

Differences in mutational signature of diffuse large B-cell lymphomas according to the primary organ.

Comprehensive molecular subtyping of diffuse large B-cell lymphoma (DLBCL) through genetic profiling has broadened our understanding of DLBCL biology. In this study, we investigated whether DLBCL, not otherwise specified (NOS) shows differences in mutational patterns depending on the primary organ. Panel-based next-generation sequencing was performed on 345 DLBCL from various primary organs, and patterns of mutations according to primary organs were analyzed. DLBCL showed a characteristic mutational signature in several primary organs. Among them, the mutational pattern of DLBCL in the breast and ileocecal area was particularly different from that of other DLBCL NOS. In breast DLBCL, MYD88L265P (57.1%), CD79B mutation (42.9%), and CDKN2A/B loss (71.4%) were found at high frequencies, which were similar to the mutation patterns of DLBCL of immune-privileged sites compared with DLBCL NOS. DLBCL in the ileocecal area showed a characteristic mutation pattern with the most frequent TP53 mutation (52.6%) and 18q21 gain (42.1%). This was also different from the mutational pattern observed in the stomach or other intestines. In discriminant analysis, DLBCL of the breast and ileocecal area tended to form separate genetic constellations from other DLBCL NOS. DLBCL NOS has a characteristic mutational profile that depends on the primary organ. In particular, the mutational signature of DLBCL in the breast and ileocecal area was heterogeneous compared with that of other DLBCL NOS. Further research is needed to determine whether primary DLBCL in the breast and ileocecal area can be classified as an independent subtype.

Clinical Features and Outcomes of Primary Breast Diffuse Large B-Cell Lymphoma: A Matched-Pair Study.

The influence of the breast as the primary site on the outcome of diffuse large B-cell lymphoma (DLBCL) and further changes in therapeutic strategies remain unclear. We aimed to compare the outcomes between primary breast and non-breast DLBCL and analyze the genetic profiles of some of the study cohorts using next-generation sequencing. This matched-pair study reviewed the medical records of 19 patients with stage I and II primary breast DLBCL diagnosed between January 2005 and December 2021 on the basis of the Wiseman and Liao criteria, and we used 1:4 propensity score matching to identify patients with non-breast DLBCL as the control group. The overall response rate, progression-free survival (PFS), and overall survival (OS) were the outcome measures. Patients with primary breast and non-breast DLBCL had a 5-year PFS of 72.6% and 86.9%, respectively (P = .206). These 2 groups also had comparable 5-year OS (86.9% vs 87.8%; P = .772). The breast as the primary site was not associated with inferior PFS (hazard ratio [HR]: 2.14; 95% CI: 0.66-6.96; P = .206) and OS (HR: 1.26; 95% CI: 0.27-5.93; P = .772). Patients with primary breast DLBCL and those with non-breast DLBCL had comparable PFS and OS under rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens. Further investigations of the mutation profile, its clinical impact, potential central nervous system relapse, and prognosis of primary breast DLBCL are required.

Impact of BCL2/MYC Protein Dual Expression and Other Clinical Factors on the Risk of Central Nervous System Progression in Patients with Primary Breast Diffuse Large B-Cell Lymphoma

Background Primary breast diffuse large B-cell lymphoma (DLBCL) has poor outcomes with frequent extranodal failures, particularly in the central nervous system (CNS). Recent studies have reported that cell-of-origin (COO), BCL2/MYC dual expression (DE), and MYC and BCL2 and/or BCL6 rearrangements, so-called double hit (DH) and triple hit, are associated with a high risk of CNS progression in DLBCL; however, the impact of these biologic markers in primary breast DLBCL on CNS progression remains unknown. Methods CNS progression was analyzed in newly diagnosed primary breast DLBCL patients identified from 2 sources: the prospective study of the Consortium for Improving Survival of Lymphoma (CISL) study group conducted from January 2012 to July 2017, and the retrospective cohort included patients who were treated outside clinical trial at any CISL institutions between January 2012 and December 2020. Briefly, the prospective study (Yhim HY et al. Cancers 2020;12:2192) included 33 patients (20-75 years of age) with primary breast DLBCL, and treatment consisted of 6 cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and 4 doses of intrathecal (IT) methotrexate (MTX) at a 3-week interval. The eligibility criteria for the retrospective cohort were virtually the same as the prospective cohort, except for no age limit. 26 patients were screened, 6 of whom were excluded because of incomplete data (n=4) and secondary breast DLBCL (n=2). Thus, the retrospective cohort included 20 patients treated with 6 cycles of R-CHOP ± radiotherapy. CNS prophylaxis was not considered for eligibility in this cohort but was done in 17 patients (4-6 doses of IT MTX [n=14] and systemic high-dose MTX [n=3]). Expert hematopathologists centrally assessed COO and DE status. COO was determined using the Hans algorithm. MYC (≥40%) and BCL2 (≥50%) protein expressions were used to assign DE. Fluorescence in situ hybridization testing was used to determine DH lymphoma. The risk of CNS progression was estimated using the cumulative incidence method. The impact of variables of interest on CNS progression was assessed using a multivariable Cox model. Results We identified 53 patients from 2 data sources. The median age was 55 years (range, 29-78), and all were female. Most patients had unilateral (n=50, 94%), localized-stage (n=48, 91%), and ECOG performance status ≤1 (n=51, 95%). Serum LDH level was elevated in 14 (26%). Hence, IPI and CNS-IPI risks were mainly low (n=45, 85%). No patients had CNS disease at diagnosis. With a median follow-up of 58.8 months (IQR, 30.3-72.9), 7 patients developed CNS progression (parenchymal only, n=4; leptomeningeal only, n=2; parenchymal and leptomeningeal, n=1). The 4-year cumulative incidence of CNS progression was 15.6% (95% CI, 6.7-27.9; Fig A). The Cox analysis revealed bilateral breast involvement (HR, 9.39; 95% CI, 1.69-52.18) was an independent factor for CNS progression in this population. Of the 53 patients, 36 were selected as a histologic data-available population because of a lack of diagnostic materials for COO and DE in 17 patients. Baseline characteristics of the histologic data-available population (n=36) were similar to the overall population (n=53). In the 36 patients with histologic data available, 4 patients had CNS progression (parenchymal only, n=2; leptomeningeal only, n=1; parenchymal and leptomeningeal, n=1), and the 4-year CNS progression rate was 14.2% (95% CI, 0.4-26.3; Fig B). According to the Hans algorithm, 30 (83%) and 6 (17%) were classified as having non-GCB and GCB, respectively. 14 patients (39%) had BCL2/MYC DE, of whom 13 were non-GCB subtype (Fig C). The CNS progression rate of non-GCB did not differ significantly from that of the GCB subtype (4-year, 17.4% vs. 0%; p=0.326), but BCL2/MYC DE had a higher risk of CNS progression than non-DE (4-year, 30.7% vs. 0%, p=0.021; Fig D). 20 patients had sufficient tissue to test DH status, but no DH cases were identified. The multivariable Cox analysis of these 36 patients showed bilateral involvement (HR, 3.73; 95% CI, 1.28-10.86) and BCL2/MYC DE (HR, 2.42×104; 95% CI, 0.51×104-10.60×104) were independent predictors for CNS progression. Conclusion Our data suggested that bilateral breast involvement and BCL2/MYC DE were independent risk factors for CNS events in patients with primary breast DLBCL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

ABCL-398 Primary Breast Diffuse Large B-Cell Lymphoma: An Indian Experience

Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare site of localized extranodal DLBCL. It represents 0.5% of all primary malignant neoplasms of the breast and around 2% of extranodal lymphomas. There is a paucity of data regarding the clinicopathologic characteristics, cell of origin, response, and outcome of treatment with uniform treatment protocol in patients from India diagnosed with PB-DLBCL. This was a retrospective study of 18 consecutive cases of PB-DLBCL registered at All India Institute of Medical Sciences between 2006 and 2021 treated with uniform 3x weekly cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) ±rituximab (R) with involved-field radiotherapy. The patients were classified as germinal center B-cell-like or activated B-cell (ABC) type using the Hans classification. The median age was 43 (21-67) years with a male:female ratio of 1:17. All the patients presented with a breast lump with a median tumor size of 5 cm. The right side was involved in 11 (61.1%) cases. Eight patients were diagnosed with lumpectomy, 9 patients with biopsy, and one patient with mastectomy specimen. Out of 18 patients, Ann Arbor: Stage I was seen in 6 (33.3%) patients, Stage IIE in 11 (61.1%) patients, and Stage 1V in 1 (5.5%) patient. B-symptoms and bulky disease were seen in 6 (33.3%) and 7 (38.8%) patients, respectively. Cell of origin data were available in 14 patients, and 11 (71.4%) were ABC in origin. Low- and intermediate-risk International Prognostic Index was seen in 42% and 48% of patients, respectively. The median number of chemotherapy cycles was 4 (3-6), rituximab was used in 10 (55.5%) cases, and CNS prophylaxis with intrathecal methotrexate was used in 10 (55.5%) cases. The complete response rate was 83.3%. After a median follow-up of 42 months, the 3-year progression-free survival and overall survival were 75% and 88%, respectively. The most common site of relapse (n=3) was parenchymal brain disease. Multimodality combination therapy (chemotherapy, immunotherapy, and radiation) can give good survival with PB-DLBCL but adding high-dose methotrexate to existing protocol needs further exploration.

Clinical Characteristics and Prognostic Factors in Primary Breast Diffuse Large B-Cell Lymphoma.

BackgroundPrimary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare subtype of non-Hodgkin lymphoma (NHL) with limited data on the clinical features and prognostic factors.Patients and MethodsA consecutive cohort of patients with PB-DLBCL was retrospectively analyzed in our hospital from February 1997 through July 2018. The primary endpoint is overall survival (OS) contributing to any cause.ResultsA total of 76 patients were diagnosed with PB-DLBCL. The median age at diagnosis was 51 years (range: 25–80 years), with female prevalence (98.7%). Forty (52.6%) patients had right-sided breast involvement but no bilateral breast involvement at diagnosis. Overall, disease stages IE and IIE were seen in 55 (72.4%) and 21 (27.6%) patients, respectively. According to the stage-modified International Prognostic Index (IPI), 37 (48.7%) patients were classified in the very good risk group (IPI 0). Of the 72 patients available, the non-germinal center B-cell (non-GCB) subtype of DLBCL was observed in 66 (91.6%) patients. All patients received anthracycline-based chemotherapy, 56 (73.7%) with rituximab, 31 (40.8%) also with additional radiation therapy, and 14 (18.4%) patients received a prophylactic intrathecal injection. Seven (9.2%) patients had refractory disease. With a median follow-up of 6.8 years (range 0.4–25.0 years), 10 (13.2%) patients had a relapse in the central nervous system (CNS) site. The 5-year and 10-year OS of all the patients was 97.2% (95% CI: 99.3–89.5) and 84.8% (95% CI: 70.0–93.5), respectively. The median OS was not reached. The median progression-free survival (PFS) was 10.3 years for patients with PB-DLBCL. The 5-year PFS of all the patients was 76.3% (95% CI: 64.6–84.6). Univariate analysis revealed several prognostic factors, including stage-modified IPI, breast surgery, refractory disease, and CNS relapse. Multivariate analyses produced two independent prognostic factors for patients with PB-DLBCL, including stage-modified IPI score (2–3 versus 0) (hazard ratio: 19.114, 95% CI 1.841 to 198.451, p=0.013) and CNS relapse (hazard ratio: 5.522, 95% CI 1.059 to 28.788, p=0.043).ConclusionIn our cohort, PB-DLBCL clinical features are similar to prior literature reports. Stage-modified IPI score and CNS relapse were associated with overall survival.

Case report: Zanubrutinib-induced dermatological toxicities: A single-center experience and review

Zanubrutinib, a next-generation non-covalent Bruton’s tyrosine kinase (BTK) inhibitor, shows great efficacy in the treatment of B cell malignancies. Some patients may experience a series of side effects after the treatment of zanubrutinib. Grade 4 dermatological toxicities are rare, which present as severe rash and skin infection. Herein, we retrospectively reported the grade 4 dermatological toxicities of zanubrutinib in three consecutive patients. They were treated with zanubrutinib 160 mg twice daily orally. One patient was diagnosed with Primary Breast Diffuse Large B-cell Lymphoma(PB-DLBCL) and two patients were diagnosed with Chronic Lymphocytic Leukemia(CLL). Within one month after zanubrutinib treatment, all three patients developed grade 4 dermatological toxicities, including bruising, maculopapular rash, petechiae, ecchymosis, hemorrhagic blister, acne-Like rash, papulopustular rash, and skin infections. Zanubrutinib was discontinued in two patients due to unacceptable dermatological toxicities. Safety data from pre-licensing clinical trials showed that zanubrutinib-related side effects were frequent but well tolerated. To date, no severe dermatological toxicities were reported. The majority of patients can be relieved with symptomatic treatment, but a very small percentage of patients may face discontinuation of the drug.

A rare case of synchronous multiple primary malignancies of breast cancer and diffuse large B-cell lymphoma that responded to multidisciplinary treatment: a case report

BackgroundMultiple primary malignancies of breast cancer and diffuse large B-cell lymphoma (DLBCL) are rare. Here, we report a case of advanced breast cancer and DLBCL managed with multidisciplinary therapy preceded by surgery with a successful outcome.Case presentationDuring a medical examination, a 71-year-old woman was diagnosed with a right breast mass, enlarged lymph nodes throughout the body, and a splenic tumor. The results of the clinical examination and imaging were suggestive of widely spread breast cancer with lymph node metastasis and malignant lymphoma with systemic metastasis. The histological evaluation of the biopsied breast tissue revealed human epidermal growth factor receptor 2 (HER2)-positive breast cancer, whereas the histological evaluation of the excised inguinal lymph node revealed DLBCL. 18F-FDG PET/computed tomography was performed, and it was determined that both breast cancer and DLBCL were in an advanced stage. Thus, mastectomy was performed, and the axillary lymph nodes showed mixed metastasis of breast cancer and DLBCL. Soon after, the R-CHOP therapy was initiated (375-mg/m2 rituximab, 2-mg/m2 vincristine, 50-mg/m2 doxorubicin, 750-mg/m2 cyclophosphamide, and 125-mg methylprednisolone). After irradiation of the spleen, trastuzumab was administered for 1 year.ConclusionsWe experienced a case of combined breast cancer and DLBCL, which was difficult to treat because both were in advanced stages. Thorough staging of the malignancy and discussion by a multidisciplinary team are necessary to determine the optimal treatment strategy.

Spontaneous remission of primary breast diffuse large B-cell lymphoma

A 71-year-old woman became aware of a 25-mm mass in her right breast as identified by her previous doctor. Needle biopsy findings suggested malignant lymphoma, and she was referred to our hospital for further evaluation. She was diagnosed with diffuse large B-cell lymphoma (DLBCL) at our hospital. Positron emission tomography-computed tomography (PET-CT) revealed an elevated SUVmax (maximum standardized uptake value; 10.3), with the mass localized in the right breast, but magnetic resonance imaging findings revealed that the mass had shrunk to 10 mm. Needle biopsy was repeated in our hospital, and lymphoma cells were absent. Two months later, CT scan revealed complete disappearance of the mass, and, since then, the patient has been free of recurrence. Although there are reports of spontaneous remission of nonHodgkin's lymphoma, it is rare in the case of high-grade B-cell lymphoma. The mechanism of spontaneous remission is unclear; however, advancing age, localized stage, activated B-cell (ABC) or nongerminal center B-cell (GCB) type, and a history of infection are the associated factors. The findings from this case suggest that DLBCL can be cured without therapeutic intervention; however, careful followup may be needed.

A case of primary breast diffuse large B cell lymphoma

Primary breast diffuse large B-cell lymphoma (DLBCL) is a rare non-Hodgkin’s lymphoma with limited data. We here report a case of primary breast diffuse large B-cell lymphoma mimicking breast cancer. A 52-year-old woman had a painless mass in her right breast. Fine needle aspiration cytology and core biopsy were performed which suggested malignant features but could not confirm the specific subtype. Excisional biopsy then was conducted revealing non-Hodgkin lymphoma, which was subsequently confirmed with histopathology and diagnosed as diffuse large B-cell lymphoma (DLBCL). A chest computed tomography scan revealed a 3.5 cm sized breast mass with skin thickening and modest lymphadenopathy in the ipsilateral axilla. The patient received six courses of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone plus rituximab) chemotherapy, then whole breast radiation (30Gy in 15 fractions). At 12 months of follow-up, the patient survives with no evidence of disease. No morbidities occurred in this patient during the follow-up period. We briefly review the current practice pattern in patients with primary breast diffuse large B-cell lymphoma.

Metachronous Diffuse Large B-Cell Lymphoma of the Breasts: A Case Report and Review of the Literature.

Introduction: Primary breast lymphoma (PBL) is a rare form of extranodal lymphoma. The most common pathology is diffuse large B cell lymphoma and most patients are diagnosed at stages 1 and 2. The therapeutic options available so far include surgery, radiotherapy, and chemotherapy Case Presentation: The patient was a 54-year old woman with localized primary breast diffuse large B-cell lymphoma (DLBCL). The patient underwent 6 courses of chemotherapy with an R-CHOP regimen followed by radiotherapy of the breast and regional lymph nodes with a dose of 40 Gy. In PET scan done three months later, the patient was in complete remission. Around one year later, the patient experienced relapse in the contralateral breast. Conclusions: In the pattern of lapse of patients, there is a tendency for extranodal relapse. In some studies it has been speculated that there is a high probability of relapse in central nervous system (CNS) and some authorities advocate CNS prophylaxis in these patients. The best outcome would be for patients treated with chemotherapy including rituximab followed by radiation. We reviewed some studies regarding treatment modalities and site of relapse.

Primary Breast Diffuse Large B-Cell Lymphoma in a 42-Year-Old Female: A Case Report and Review of Literature

Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare localized extranodal lymphoma. It is mainly diagnosed by pathological examination due to the lack of specific clinical and imaging manifestations. Whole-body positron emission tomography-computed tomography (PET-CT) is widely used in determining clinical staging and guiding clinical treatment. As part of comprehensive treatment, targeted therapy with rituximab, intrathecal methotrexate injection and consolidation radiotherapy remain controversial in treating PB-DLBCL, but the comprehensive treatment based on full-course of chemotherapy is still widely used as the first-line treatment. Comprehensive treatment often leads to a sharp decline in the immunity of elderly patients with malignancy. In this situation, surgery may be a good chance to improve their life quality without serious complications. We present a rare case of PB-DLBCL during the coronavirus disease 2019 (COVID-19) pandemic. The patient underwent chest CT scan to screen COVID-19 and a mass of left breast was accidentally found. Because of the city lockdown policy in Wuhan, she did not seek medical help until noticing that the mass was gradually enlarged. Both ultrasonography and mammography indicated that the lesion was breast cancer. However, ultrasound-guided core needle biopsy revealed diffuse large B-cell lymphoma of breast and PET-CT scan showed that the lesion was a primary hypermetabolic tumor of left breast. The patient subsequently received comprehensive treatment based on six cycles of rituximab-cyclophosphamide, hydroxydaunomycin, oncovin, prednisone (R-CHOP) chemotherapy. J Med Cases. 2021;12(5):181-185 doi: https://doi.org/10.14740/jmc3660

Abstract OT-05-01: Fine-sliced neurocognitive assessments and high-resolution neuroimaging biomarkers to diagnose cancer- and chemotherapy-induced cognitive deficits (CCICD) - a pilot study

Abstract Background: Significant progress has been made in cancer survival, however there is much room for improvement in supportive cancer care. “Chemo-brain” is the lay language that some patients use to describe a cognitive fog or mental fuzziness that they experience soon after chemotherapy (CT) and that can last more than a decade after CT has ended. In this study, we examine the notion of accelerated cognitive aging as a potential side effect of cytotoxic CT.While CCICD has been widely researched, its underlying biological mechanisms are yet to be sufficiently elucidated. The long-range goals of this study are to (a) yield clinically valid diagnostic criteria for CCICD by the identification of fine-sliced neurocognitive measures that can reliably capture within-subject, nuanced, cognitive changes pre/post CT; and (b) identify brain-based biomarkers that can leverage future systemic therapies or adjunctive medications that are neuroprotective. Trial design: The study takes advantage of greater clarity offered by high-resolution neuroimaging (7Tesla) to delve into biomarkers associated with the neurotoxic effects of the common chemotherapeutic agents doxorubicin, paclitaxel, docetaxel, and cyclophosphamide on brain metabolism and iron homeostasis, which may result in CCICD. We innovate by harnessing magnetic resonance spectroscopy (MRS) together with quantitative susceptibility mapping (QSM) and diffusion tensor imaging (DTI), a trio that has rarely been combined in 7T imaging, to uncover biomarkers related to CCICD. In this high-resolution imaging environment, we hope to individually isolate and track changes in key neuronal metabolites such as glutamate and glutamine using MRS (pre- and post-CT), in a prospective, longitudinal study. At these two time-points, we simultaneously use QSM to identify regions of increased iron deposits (associated with doxorubicin) in the brain along white matter tracts as well as DTI to assess white matter degeneration.We selected fine-sliced measurements of cognitive updating, mental flexibility and impulse control, the key executive function (EF) deficits associated with CCICD. These and other global EF measures are administered pre/post-CT (within a period of 4-6 months), while assessments of depression, anxiety, sleep, and pain will be administered via a weekly online questionnaire during CT.Eligibility criteria: Eligible patients are adults (age ≥18) with either early stage HER2 negative breast cancer or diffuse large B-cell lymphoma who will receive curative-intent combination CT, to include cyclophosphamide. Patients are excluded if they have a prior history of cancer diagnosis or treatment. Patients would have to be 7T MRI compatible.Specific Aims: To obtain preliminary estimates of the change in EF measures, brain metabolite, iron concentrations, and white matter degeneration in patients pre- and post-CT, to inform a subsequent larger trial.Statistical methods: The proposed sample (N=9) size achieves 74.8% power to detect a 1 SD change with a significance level of 0.05 using a two-sided, one-sample t-test for the pairwise difference. Estimates and 95% confidence intervals will be reported. Additionally, the relationship between executive function, brain metabolite, iron concentrations and white matter degeneration will be explored. Present and Target accrual: Accrual has thus far been delayed, partially due to due to COVID-19 restrictions on clinical research, beginning in March 2020. Target accrual is 9 patients.Contact information: Kanchna-ramchandran@uiowa.edu, Phone: 319-356-0535. Citation Format: Kanchna Ramchandran, Sneha Phadke, Sarah Mott, Grerk Sutamtewagul, Mark Karwal, Vince Magnotta. Fine-sliced neurocognitive assessments and high-resolution neuroimaging biomarkers to diagnose cancer- and chemotherapy-induced cognitive deficits (CCICD) - a pilot study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-05-01.

METABOLIC SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY WITH THE NEW RADIOPHARMACEUTICAL ⁹⁹ᵐTc-1-thio-D-glucose IN THE DIAGNOSIS AND MONITORING OF THE PRIMARY BREAST LYMPHOMA (CASE REPORT)

The article shows the feasibility of detecting and monitoring primary breast diffuse large B-cell lymphoma using single-photon emission computed tomography (SPECT) with 99mTc-1-thio-D-glucose (99mТс-TG), a new radiopharmaceutical. The innovative radiopharmaceutical makes it possible to evaluate the metabolism of tumor tissue without using positron emission tomography. The findings of 99mTc-TG SPECT obtained during diagnosis and monitoring of the patient were confirmed by the results of computed tomography. A comprehensive examination of the patient, including 99mTc-TG SPECT, made it possible to diagnose a rare case of primary breast lymphoma. Primary breast lymphoma accounts for 1.7–2.2 % of all extranodal nonHodgkin lymphomas. Diffuse large B-cell lymphoma is the most common histological type occurring usually as a unilateral palpable tumor in middle-aged women. Extranodal lymphomas account for less than 0.5 % of all malignant neoplasms of the breast. After 6 courses of immunochemotherapy, the patient underwent 99mTc-TG SPECT, which demonstrated persistent hypermetabolic activity in the breast. The patient received radiation therapy to the remaining tumor of the left breast. The patient is in remission and followed up at the Cancer Research Institute of Tomsk National Research Medical Center. Thus, 99mTc-TG SPECT is believed to be a promising method for visualizing primary breast lymphomas and assessing their treatment outcomes. It is an alternative to the standard approach using 18F-FDG positron emission tomography. The method compares favorably with positron emission tomography with its wide availability and low cost of study. 

METABOLIC SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY WITH THE NEW RADIOPHARMACEUTICAL ⁹⁹ᵐTc-1-thio-D-glucose IN THE DIAGNOSIS AND MONITORING OF THE PRIMARY BREAST LYMPHOMA (CASE REPORT)

The article shows the feasibility of detecting and monitoring primary breast diffuse large B-cell lymphoma using single-photon emission computed tomography (SPECT) with 99mTc-1-thio-D-glucose (99mТс-TG), a new radiopharmaceutical. The innovative radiopharmaceutical makes it possible to evaluate the metabolism of tumor tissue without using positron emission tomography. The findings of 99mTc-TG SPECT obtained during diagnosis and monitoring of the patient were confirmed by the results of computed tomography. A comprehensive examination of the patient, including 99mTc-TG SPECT, made it possible to diagnose a rare case of primary breast lymphoma. Primary breast lymphoma accounts for 1.7–2.2 % of all extranodal nonHodgkin lymphomas. Diffuse large B-cell lymphoma is the most common histological type occurring usually as a unilateral palpable tumor in middle-aged women. Extranodal lymphomas account for less than 0.5 % of all malignant neoplasms of the breast. After 6 courses of immunochemotherapy, the patient underwent 99mTc-TG SPECT, which demonstrated persistent hypermetabolic activity in the breast. The patient received radiation therapy to the remaining tumor of the left breast. The patient is in remission and followed up at the Cancer Research Institute of Tomsk National Research Medical Center. Thus, 99mTc-TG SPECT is believed to be a promising method for visualizing primary breast lymphomas and assessing their treatment outcomes. It is an alternative to the standard approach using 18F-FDG positron emission tomography. The method compares favorably with positron emission tomography with its wide availability and low cost of study. 

First-Line Treatment for Primary Breast Diffuse Large B-Cell Lymphoma Using Immunochemotherapy and Central Nervous System Prophylaxis: A Multicenter Phase 2 Trial.

There are limited data from prospective controlled trials regarding optimal treatment strategies in patients with primary breast diffuse large B-cell lymphoma (DLBCL). In this phase 2 study (NCT01448096), we examined the efficacy and safety of standard immunochemotherapy and central nervous system (CNS) prophylaxis using intrathecal methotrexate (IT-MTX). Thirty-three patients with newly diagnosed primary breast DLBCL received six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and four fixed doses of IT-MTX (12 mg). The median age was 50 years (range, 29–75), and all patients were females. According to the CNS-International Prognostic Index, most patients (n = 28) were categorized as the low-risk group. Among the 33 patients, 32 completed R-CHOP, and 31 completed IT-MTX as planned. With a median follow-up of 46.1 months (interquartile range (IQR), 31.1–66.8), the 2-year progression-free and overall survival rates were 81.3% and 93.5%, respectively. Six patients experienced treatment failures, which included the CNS in four patients (two parenchyma and two leptomeninges) and breast in two patients (one ipsilateral and one contralateral). The 2-year cumulative incidence of CNS relapse was 12.5%. Although standard R-CHOP and IT-MTX without routine radiotherapy show clinically meaningful survival outcomes, this strategy may not be optimal for reducing CNS relapse and warrants further investigation.

A multicentre retrospective study of primary breast diffuse large B-cell and high-grade B-cell lymphoma treatment strategies and survival

ABSTRACT Objectives: Primary breast diffuse large B-cell lymphoma (PB-DLBCL) and primary breast high-grade B-cell lymphoma (PB-HGBCL) are rare extranodal aggressive B-cell lymphomas with distinct characteristics. Reliable data regarding appropriate treatment of these specific entities are lacking due to their rarity. Methods: We reviewed 36 patients diagnosed at four Chinese medical centres between January 2008 and December 2018. Data regarding clinicopathological features, therapeutic evaluation and central nervous system (CNS) relapse were collected, and overall survival (OS) and progression-free survival (PFS) were calculated. Results: Among the 36 patients, there were 29 PB-DLBCL patients and 7 PB-HGBCL patients. The 5-year OS for PB-DLBCL and PB-HGBCL was 75.9% and 28.6%, respectively. The 5-year PFS for PB-DLBCL and PB-HGBCL was 69.0% and 14.3%, respectively. The R-DAEPOCH regimen was significantly more effective in PB-DLBCL patients than the R-CHOP regimen (5-year OS: 78.9% vs 62.5%, P=0.024; 5-year PFS: 73.7% vs 50.0%, P=0.037) but resulted in more severe myelosuppression (P=0.025). The rate of CNS relapse was 17.2% in PB-DLBCL patients and 28.6% in PB-HGBCL patients; the difference was not significant (P=0.602). The R-DAEPOCH regimen did not predominantly reduce CNS recurrence as expected (P=0.616). The Cox proportional hazards model revealed that risk stratification and triple expression were independent prognostic factors. Conclusion: Current treatments, including more intensive chemotherapy regimens, achieve good control of the disease. Novel drugs combined with cellular immunotherapy initially show promising therapeutic effects, and more clinical trials are required to confirm these effects further.

A novel classification based on B-cell receptor signal gene expression correlates with prognosis in primary breast diffuse large B-cell lymphoma.

Primary breast diffuse large B-cell lymphoma (PB-DLBCL), the most common histologic subtype of lymphoid malignancy in the breast, is a clinically and genetically heterogeneous disease that has insufficient systematic studies on the pathological and molecular features, optimal treatment scheme, as well as the prognostic factors. The aim of our study was to identify biomarkers and distinct subtypes of PB-DLBCLs and then evaluate the prognosis of this rare malignant lymphoma. We carried out hierarchical clustering analysis to evaluate protein expressions of potential biomarkers detected by immunohistochemistry staining of samples from 68 PB-DLBCL patients. The gene expression data from TCGA database was obtained to validate the identified clusters. We identified three robust clusters based on the B-cell receptor (BCR) signaling pathway, including two recognized NF-κB-dependent and PI3K-dependent clusters, and a distinct subset of PB-DLBCL with NF-κB-independent anti-apoptotic overexpression plus PI3K signaling, which exhibited an evolving definition and distinctive characters of a cluster group. Furthermore, survival analysis results showed an inferior outcome in NF-κB-dependent cluster patients and favorable survival in the PI3K-dependent cluster patients, suggesting an important predictive value of the three clusters. Our study provided a new perspective for understanding clinical complexity of PB-DLBCLs, and gave evidence for finding targeted biomarkers and strategies.