bluuebunny/crossref_metadata_2025 huggingface dataset:
The ratio of PD1+CD8+T cells in stromal area of tumor tissue is associated with the effect of neoadjuvant chemotherapy in HER2 negative breast cancer patients.
Authors: Gong Chang , Lin Qun , Cen Yinghuan , Fang Xiaolin , Shi Yu , Chen Letian , Luo Qing , Duan Zhuxi
Published: June 2022

e12626

Background: For patients diagnosed with early breast cancer, surgery remains the standard of care. Early patients achieving pathological complete response (pCR) after neoadjuvant therapy have been proved to be associated with improved survival. However, the accurate prediction of pCR in a clinical setting remains challenging. Tumor infiltrating lymphocyte (TIL) levels have recently been identified as an independent predictor of pCR in breast cancer. However, due to extremely complex tumor microenvironment within tumor, the role of different immune cell subtypes in neoadjuvant chemotherapy (NAC) is inconclusive. This study aimed to explore the potentially predictive role and dynamic changes of immune cell subsets in patients with HER2 negative breast cancer receiving NAC. Methods: Since January 2020, tumor tissue samples of 12 HER2 negative breast cancer patients were collected at baseline and after NAC. Several kinds of immune cells including CD3+T cells, CD4+T cells, CD8+T cells, PD-1+CD8+T cells, Tregs, M1/M2 tumor associated macrophages(TAM), PD-L1+CD68+TAM, B cells, CD56bright NK cells and CD56dim NK cells in the tumor tissue were evaluated by multiple fluorescence immunohistochemistry (mIHC) and counted in intratumoral and stromal area for density and ratio. T test was used for the comparison of immune cells and statistical significance was set at p = 0.05. Results: We examined immune cell subtypes and PD-L1/PD-1 expression of 12 HER2 negative breast cancer patients. According to achieving pCR or not, these 12 patients were divided into two groups, pCR (n = 3) and non-pCR group (n = 9). The results showed that the ratio of PD1+CD8+T cells in stromal area of baseline tumor tissue of pCR group was significantly higher than non-pCR group (median ratio, pCR group vs. non-pCR group = 17.3% vs. 3.6%, p = 0.029).In addition, the ratio of PD1+CD8+T cells in stromal area of pCR group was still significantly higher than that of non pCR patients after NAC (median ratio, pCR group vs. non-pCR group = 20.7% vs. 2.6%, p = 0.0003). Conclusions: Whether at baseline or after NAC, the ratio of PD1+CD8+T cells in stromal area is associated with the effect of NAC in HER2 negative breast cancer.
Real-world PARPi treatment patterns and outcomes among patients with metastatic breast cancer.
Authors: Dawood Shaheenah S. , Brzozowski Kaylen
Published: June 2022

e13005

Background: PARP inhibitors (PARPi) improves PFS among patients (pts) with HER2-ve metastatic breast cancer (MBC) and a BRCA1/2 mutation compared to physician choice of chemotherapy. The objective of this retrospective analysis was to look at the prognostic outcome associated with the use of PARPi therapy among pts with MBC in the real world setting. Methods: We utilized a federated network of de-identified health data representing approximately 84 million pt lives available through the TriNetX Research Network. We identified 767 pts with MBC treated with a PARPi. Overall survival (OS) was computed using the Kaplan Meier product limit method. Propensity score matching was performed on all comparisons of OS. Matching variables included age groups, prior platinum therapy, prior genitourinary malignancies, and secondary metastasis location. Results: Mean age was 56.3yrs. 718 pts had HER2- disease and 49pts had HER2+ disease. Median OS was 55.0m and 44.4m among pts with HER2- and HER2+ disease respectively. Median OS among was 58.3m and 48.6m among patients with HR+/HER2- and TNBC respectively(p = 0.18). Among pts with HR+/HER2- disease, 50.2% received PARPi in combination with endocrine therapy and 43.5% received CDK4/6i. Median OS among pts who received CDK4/6i + endocrine therapy prior to a PARPi and those that never received a CDK4/6i was 55.1m and 36.9m, respectively(p = 0.01). Among pts with TNBC, median OS among those that received PARPi prior to chemotherapy compared to those who received PARPi after chemotherapy was 52.5m and 47.6m respectively (p = 0.97). 169 HER2- pts had brain metastases. Median OS among pts who had brain metastases was 36.9m among pts with HR+/HER2- disease and 22.5m among pts with TNBC(p = 0.01). Among pts with no brain metastases, median OS was 60.6m among pts with HR+/HER2- disease and 56.3m among pts with TNBC(p = 0.91). Median OS among pts who were rechallenged with a PARPi compared to those who were not rechallenged with a PARPi was 58.3m vs 42m respectively (p = 0.05). Conclusions: To our knowledge this is the first data set to report activity of CDK4/6i among pts with HR+/HER2- MBC who received a PARPi, with an observed 18m OS advantage compared to pts who did not receive a CDK4/6i. In absence of brain metastases OS of pts with TNBC and HR+/HER2- is similar when treated with a PARPi.
The prognostic value of genetic alterations of gasdermin (GSDM) family genes in breast cancer.
Authors: Ding Zhenyu , Huang Tanxiao , Chen Juan , Gao Jinping , Yang Jiangjie , Liu Ming , Liu Yuanyuan , Chen Shifu , Piao Ying
Published: June 2022

e13006

Background: Breast cancer (BC) is the most commonly diagnosed cancer in 2021, with an estimated 2.9 million new cases (31%) and the second leading cause of cancer death in women. Gasdermins are encoded by six paralogous genes: GSDMA, GSDMB, GSDMC, GSDMD, GSDME (also known as DFNA5) and DFNB59 (also known as pejvakin, PJVK). They play a key role in pyroptosis. Few studies addressing the association between genetic alterations in the GSDM family genes and breast cancer prognosis have been reported up to now. Methods: We used a public cancer research platform named cBioPortal to analyze a cohort of 1983 breast cancer samples. We defined overall survival (OS) as the time between the procedure date when the tumor specimen was collected and the date of death or last follow-up visit. We compared the survival curves of two groups using Kaplan-Meier method and log-rank tests. The statistical significance level was set to 5% (p < 0.05). Results: These genes were found in 685 (34.5%) samples with various genetic alterations, including missense mutation, splice mutation, truncating mutation, structural variant, amplification, deletion. GSDMC was the most frequently altered gene (18%), followed by GSDMD (17%), GSDMB (11%), GSDMA (10%), GSDME (2.5%), and PJVK (0.7%). Based on the result, patients were divided into the GSDM mutation and non-GSDM mutation group. The median OS of the GSDM mutation group was 124.57 months (Table), which is significantly shorter than the OS of the non-GSDM mutation group (log-rank test p = 5.64e-7). Conclusions: To our best knowledge, this analysis is the first investigation to evaluate the association between prognostic value and genetic alterations in GSDM family genes in breast cancer patients. Our investigation shows that genetic alterations in GSDM family genes can be used to predict poor prognosis in breast cancer patients. Further studies are warranted to verify and expand on these findings.[Table: see text]
The prognostic significance of disseminated tumor cells in bone marrow in patients with operable breast cancer: An updated analysis.
Authors: Dirix Luc Yves , Van Mileghem Laura , Prove Annemie , Vermeulen Peter B.
Published: June 2022

e13013

Background: The main cause of death in breast cancer patients is the consequence of the spread and outgrowth of tumor cells at distant sites. The presence of disseminated tumor cells (DTCs) in the bone marrow at diagnosis is considered a predictor for metastasis. Methods: This is an updated analysis of a study in 102 patients with operable breast cancer on the significance of bone marrow micrometastases. The mean follow-up time is 127 months (range 10 - 142, median 129 months). Bone marrow aspirates were analysed for the presence of DTCs by a real time-polymerase chain reaction (RT-PCR) for cytokeratin 19 (CK) and mammaglobin (MAM).The aim of this study is to confirm the association between DTCs and disease-specific survival (DSS) as well as metastasis-free survival (MFS). Results: CK positivity was borderline significant for DSS (p = 0.054). MAM positivity was significantly prognostic for DSS with a hazard ratio (HR) of 3,110 (1,416-6,832) (p = 0,005). Patients positive for both CK and MAM did have a significant worse outcome with a HR for DSS of 7,329 (2,361 – 22,752) (p = 0,001). No significant influence on MFS was identified for CK (p = 0,658) or MAM positivity (p = 0,095). The combination of CK and MAM positivity did however confer a significantly increased risk for MFS (p = 0,043) at a HR of 4,126 (1,409-12,082). Conclusions: This study confirms the role of DTCs as a negative, prognostic factor in patients with operable breast cancer. The combination of CK and MAM is useful to identify this increased risk.
Tyrosine kinase inhibitors (TKIs) in trastuzumab emtansine (T-DM1) resistant HER2-positive metastatic breast cancer: A real-world study.
Authors: Yin Yongmei , Sun Chunxiao , Hua Yijia , Jiang Mengping , Yang Fan , Wu Xinyu , Zeng Tianyu , Bao Shengnan , Liang Yan , Huang Xiang , Li Wei
Published: June 2022

e13029

Background: Trastuzumab emtansine (T-DM1) has shown great effectiveness in treating HER2-positive metastatic breast cancer, but therapies subsequent to T-DM1 progression are still controversial. Here, we investigated efficacy and safety of tyrosine kinase inhibitors (TKIs) based therapy in T-DM1 resistant HER2-positive metastatic breast cancer. Methods: From August 2019 to February 2022, 53 HER2-positive metastatic breast cancer patients received TKIs-based therapy after T-DM1 progression in Jiangsu Province Hospital. We reported progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and safety profiles of TKIs in treating T-DM1 resistant HER2-positive metastatic breast cancer. Results: 53 patients received TKIs-based therapies as a second or later line therapy. 51 (96.2%) patients received a combined therapy, including TKIs plus capecitabine, vinorelbine or trastuzumab. 2 (3.7%) patients received TKIs alone. The median follow-up time was 19.7 months (95%CI 14.829-24.571). The median PFS was 10.6 months (95%CI 5.530-15.670). OS has not reached. ORR was 18.9% and CBR was 72.5%. For patients who had brain metastasis (n = 12), the median PFS was 10.5 months (95%CI 7.406-13.594) and intracranial ORR was 33.3%. Compared with lapatinib (n = 30), pyrotinib (n = 21) provided a better PFS, but no significant difference was observed (8.0 months vs. 19.0 months, P = 0.076). The most common adverse events were thrombocytopenia (12, 22.6%), hand-foot syndrome (11, 20.8%) and diarrhea (6, 11.3%). Conclusions: TKIs-based therapy could improve the survival of T-DM1 resistant HER2-positive metastatic breast cancer patients, including those with brain metastasis. This provides a novel therapeutic option for HER2-positive breast cancer treatments.
Anti-HER2 antibody inetetamab plus camrelizumab and utidelone for pretreated HER2-positive advanced breast cancer: A single-arm, multicenter, phase 2 study.
Authors: Yan Min , Lv Huimin , Niu Limin , Zhang Mengwei , Zeng Huiai , Zhao Shengnan , Wang Jing , Sun Huihui , Chen Shumin
Published: June 2022

e13030

Background: Treatment options for patients with HER2-positive breast cancer after progression on two or more lines of HER2-directed therapies are scarce. Inetetamab, a novel anti-HER2 antibody, exhibits the same binding affinity to HER2 antigen and antibody-dependent cell-mediated cytotoxicity as trastuzumab. Previous studies have demonstrated the treatment potential of PD-1 inhibitor combined with HER2-targeted therapy in HER2-positive gastric or gastroesophageal junction cancer. Utidelone, a genetically engineered epothilone analogue, has shown promising efficacy in heavily pretreated metastatic breast cancer. This study aimed to investigated inetetamab plus camrelizumab (anti-PD-1 antibody) and utidelone in patients with HER2-positive recurrent or metastatic breast cancer who had progressed after at least two lines of HER2-directed therapies with trastuzumab and tyrosine kinase inhibitors (TKIs). Methods: In this phase 2 study (NCT04681287), patients received intravenous camrelizumab (200 mg once every 3 weeks), inetetamab (8 mg/kg loading dose then 6 mg/kg, day 1), and utidelone (30 mg/m2, days 1-5) until disease progression or intolerable toxicity. The primary endpoint was 3-month progression-free survival (PFS) rate according to the Response Evaluation Criteria In Solid Tumors, version 1.1. Secondary endpoints included objective response rate (ORR), PFS, overall survival, and safety. Simon’s two-stage design was adopted for this study. Results: Between April 2021 and January 2022, a total of 27 patients were enrolled. As of January 2022, 20 patients could be analyzed. The median number of previous systemic therapies for advanced disease was three. Previous HER2-targeted therapies included trastuzumab (20 [100%]), pyrotinib (17 [85%]), lapatinib (7 [35%]), pertuzumab (3 [15%]), and margetuximab (2 [10%]). The first stage required 10 patients, and 8 of them were free from progression at 3 months. The study proceeded to the second stage for another 31 patients, and the accrual is ongoing. The 3-month PFS rate in 20 patients was 75%. The ORR was 30% (6/20); one (5%) patient achieved complete response. The most common treatment-related adverse events (TRAEs) were peripheral neuropathy (19 [98%]), capillary proliferation (19 [98%]), alopecia (18 [90%]), and fatigue (7 [35%]). Grade ≥3 TRAEs included peripheral neuropathy (2 [10%]) and rash (1 [5%]). No treatment-related treatment discontinuation or deaths occurred. Conclusions: Inetetamab plus camrelizumab and utidelone showed promising efficacy and acceptable safety profile in patients with HER2-positive advanced breast cancer after progression on at least two lines of HER2-directed therapies with trastuzumab and TKIs. Clinical trial information: NCT04681287.
Prognostic factors influencing progression-free survival in HER2 positive metastatic breast cancer patients who treated with lapatinib and capecitabine combination.
Authors: Dogan Izzet , Paksoy Nail , Ak Naziye , Vatansever Sezai , Saip Pinar , Aydiner Adnan
Published: June 2022

e13031

Background: Her2 positivity is detected in about 20% of breast cancer patients. After trastuzumab-based therapy, lapatinib and capecitabine combination is a treatment option in HER2-positive metastatic patients. The study aimed to evaluate the prognostic factors in HER2 positive metastatic breast cancer patients treated lapatinib and capecitabine combination. Methods: We evaluated data of the HER2 positive metastatic breast cancer patients who were treated with lapatinib and capecitabine retrospectively. The patients' clinical, pathological, and treatment features were recorded from the hospital database. Kaplan Meier and Cox regression analysis were used for survival analysis. Results: 102 patients were included in the study. The median age was 47 (range, 24-87), and 99 (97.1%) patients were female. The number of de-novo metastatic patients was 44 (43.1%). The most common metastatic sites were bone (62.4%), brain (58.6%), liver (35.6%), and lung (34.7%), respectively. All patients were previously treated with trastuzumab-based chemotherapy. 44 (44.1%) patients received hormonotherapy (tamoxifen or aromatase inhibitor), and 23 (22.5%) patients palliative radiotherapy. Complete response was 8.2%, partial response 32%, and stable disease 25.8% with lapatinib and capecitabine combinations. At a median follow of 11.6 months, progression-free survival was 8 (95% CI, 5.1-10.8) months. In multivariate analysis, age (p = 0.020), de-novo metastatic disease (p = 0.028), and endocrine therapy (p = 0.020) were statistically significant prognostic factors for progression-free survival. However, history of breast surgery (p = 0.060), number of chemotherapy used with trastuzumab (p = 0.338), number of metastatic sites (p = 0.257), and palliative radiotherapy (p = 0.394) were not significant. Conclusions: We showed real-life outcomes of the lapatinib and capecitabine combination in metastatic HER2-positive breast cancer patients. Also, we detect that being under age 50 years, de-novo metastatic disease, and hormone-negative tumor were poor prognostic factors of progression-free survival.
The role of RARRES2 in regulating lipic metabolic reprogramming in the development of brain metastases in triple negative breast cancer.
Authors: Li Yiqun , Sun Fangzhou , Li Chunxiao , Mo Hongnan , Qian Haili , Ma Fei
Published: June 2022

e13047

Background: Triple negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is characterized by a high incidence of brain metastases (BM) and a poor prognosis. As the most lethal form of breast cancer, brain metastases remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies. Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastases (BCBM), but the underlying mechanisms are far from been fully elucidated. Methods: Using public datasets and our single-cell transcriptome sequencing data, we identified and verified the specific down-regulation of RARRES2, a multifunctional adipokine and chemokine, in brain metastases of triple negative breast cancer. We investigated the effect of aberrant RARRES2 expression on brain metastases in both in vitro and in vivo studies. Key signaling pathway components were evaluated using qPCR and Western blot analysis. Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2. Results: We show for the first time that down-regulation of RARRES2 is specifically associated with BCBM, and that RARRES2 promoted BCBM through lipid metabolic reprogramming. Mechanistically, reduced expression of RARRES2 in brain-tropic triple negative breast cancer cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols (TAGs) by regulating PTEN-PI3K-SREBP1 signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment. Conclusions: Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of brain metastases, thereby offering potential therapeutic targets for BCBM in TNBC.
Supporting patients with metastatic breast cancer during therapy with cyclin-dependent kinase 4/6 (CDK) inhibitors: A needs assessment.
Authors: O'Sullivan Ciara Catherine Maria , Jacobs Ginny , Perez Domingo Gregorio , Jackson Katrina , Schowengerdt Bethany , Lazure Patrice , McFadden Pam
Published: June 2022

e13054

Background: Combination therapy with cyclin dependent kinase 4 and 6 inhibitors (CDK4/6i: palbociclib, ribociclib and abemaciclib) and endocrine therapy (ET) has markedly improved treatment of hormone receptor positive (HR+), HER2-negative (-) advanced or metastatic breast cancer (MBC) worldwide.However, data is limited on why patients may discontinue CDK4/6i based therapy and how healthcare providers (HCPs) see their role in educating patients (Px) about side effects and supporting compliance. Objective: This study identifies reasons for suboptimal compliance and early discontinuation of CDK4/6i in US HR+ HER2- MBC Px, with a focus on HCPs and Px educational needs related to on-treatment monitoring, side effects and symptom management. Methods: A sequential mixed-methods design was used; 45-minute phone interviews (n=25) informed the development of an online survey (n=193). Both phases included HCPs comprising medical oncologists (ONCs), oncology registered nurses (RNs), nurse practitioners, and physician assistants (NPs/PAs) in community-based settings. Results: Identified areas of improvement for HCPs included: suboptimal competencies were identified: educating Px adequately regarding potential side effects and engaging them to monitor, report, and address them. Among HCPs surveyed, 26%-48% reported suboptimal knowledge of side effects of specific CDK4/6i [Table]. Interviewees noted that educating Px and setting expectations on potential side effects was critical, but 52% of ONCs reported suboptimal skill doing so. A majority of HCPs (68%-91%) expect Px to be able to report all side effects, with half of ONCs considering compliance with medication entirely Pxs’ responsibility, compared with NPs/PAs and RNs at 16-17%. Conclusions: This study identified areas where HCPs can improve their ability to counsel Px and address concerns that may influence a Px’s decision to prematurely discontinue therapy and should be used to inform future professional development initiatives. [Table: see text]
Increased lung metastasis with sevoflurane in breast cancer surgery is associated with VEGF and elevated vascular permeability by VEGF in a mouse model of human breast cancer.
Authors: Lin Jun , Li Ru , Huang Yujie , Dilger James P. , Beto Mukherjee Mousumi
Published: June 2022

e13060

Background: An on-going controversy is whether general anesthetics used in cancer surgery substantially influence the outcome of cancer patients. Thousands of cancer patients undergo surgery with hope of cure. However, postoperative metastasis remains a deadly disease that affects millions of lives, even with all the recent therapeutic advancements. Anesthesia is required for surgical resection of solid tumors and we have shown that general anesthetics substantially influences the process of breast cancer lung metastasis through increasing pulmonary permeability in animal models. Our previous study demonstrates that inhaled anesthetic sevoflurane used during resecting primary breast tumors promotes lung metastasis via IL6 pathway in syngeneic model of murine 4T1 breast cancer cells, compared with an intravenous anesthetic propofol. Methods: Xenograft model of human MDA-MB 231 breast cancer of spontaneous metastasis was utilized in this study to evaluate the effect of commonly used general anesthetics including sevoflurane and propofol on breast cancer lung metastasis and explore the potential mechanism. Results: In this study we show that the metastatic promoting effect of sevoflurane is associated with elevated secretion of VEGF and increased vascular permeability in xenograft model of human MDA-MB 231 breast cancer of spontaneous metastasis. Cytokine array profiling reveals that the mice receiving sevoflurane have increased levels of pro-angiogenic factor VEGF in serum and lung tissues. Sevoflurane enhances the expression level of VEGFR on HUVEC cells. Furthermore, sevoflurane disrupts endothelial monolayer in vitro and elevates pulmonary vascular permeability in vivo. The sevoflurane-promoted breast cancer lung metastasis is reversed by DC101, an antibody targeting mouse VEGFR-2. Conclusions: Our results show that the inhaled anesthetic sevoflurane during surgical removal of primary tumor alter the course of metastasis through regulating secretion of VEGF and associated vascular remodeling. The mechanistic study of general anesthetics on cancer cell metastasis establishes the causal link and could provide the potential therapeutic intervention and guide the clinical trials.
Bacterial community composition in breast cancer subtypes.
Authors: Chan Alfred , Naseem Madiha , Onyshchenko Mykola , Lee Delphine
Published: June 2022

e13063

Background: Breast cancer is a heterogeneous disease with multiple molecular subtypes and prognostic outcomes. Among these subtypes, Luminal-A is enriched with estrogen receptor and has the best clinical prognosis, whereas triple-negative breast cancer (TNBC) remains an aggressive subtype with poor prognosis. Changes in the diversity of breast microbiome have been associated with breast cancer initiation and progression. We hypothesized that Luminal-A and TNBC subtypes will have differences in both bacterial community composition as well as differences in microbial genomes and pathways. Methods: 6 Luminal-A and 6 TNBC FPPE tissue blocks were processed for both 16S V4 rRNA amplicon sequencing and shotgun metagenomics sequencing. 16S sequencing data was processed using mothur (v1.44.3) and reads were assigned taxonomy against the SILVA 16S rRNA database (v132). Shotgun sequencing was processed using the EBI-Metagenomic (v5) pipeline; bacterial identification was performed using the Kraken pipeline. Results: Shannon alpha-diversity or species enrichment, was significantly higher in Luminal-A compared to TNBC (nonparametric, P = 0.008) and their microbiome composition was significantly different by beta-diversity analysis (bray-curtis dissimilarity, PERMANOVA, P = 0.014). Bacteroides and Sphingomonadaceae species were significantly higher in abundance in Luminal-A, compared to Pseudomonas and Neisseriaceae species abundance in TNBC. Results were validated by shotgun sequencing. Luminal-A and TNBC bacterial metabolic pathways were not statistically different overall (PERMANOVA, P = 0.312). Pathways associated with Luminal-A included Response to Wounding (GO: 0009611), tRNA modification (GO: 0006400), and Cytoplasmic Microtubule Organization (GO: 0031122). Pathways associated with TNBC included troponin complex (GO: 0005861), rRNA processing (GO: 0006364), and CDC73 PAF1 (GO: 0016593). Conclusions: Using both shotgun and amplicon sequencing, this is the first analysis to show that Luminal-A and TNBC subtypes have statistically significant differences in bacterial species composition. Luminal-A had higher species diversity and abundance of Sphingomonadaceae, which are associated with healthy breast tissue and better clinical outcomes. TNBC had lower species diversity and abundance of Pseudomonas and Neisseriaceae, which have been associated with tumor survival and cell growth. Understanding the role of microbiota and its complex interaction with tumor microenvironment could help identify new treatment targets in breast cancer subtypes, and warrants further investigations.
Efficacy of sacituzumab govitecan based regimen in triple-negative breast cancer: A systematic review.
Authors: Khalid Farhan , Kashyap Richi , Singh Vinit , Tayyeb Muhammad , Jaan Ali , Mohan Gaurav , Meghal Trishala
Published: June 2022

e13068

Background: Sacituzumab govitecan (SG) is an drug-antibody conjugate composed of anti-trophoblast cell-surface antigen 2 (Trop-2) IgG1 Kappa antibody with SN-38 through a hydrolysable linker. SG has a promising efficacy safety profile in triple negative breast cancer (TNBC) and was given regular approval for nonresectable locally advanced or metastatic disease with 2 or more previous line of therapies. This review aims to explore the efficacy and safety of SG-regimens for the treatment of TNBC. Methods: We conducted a literature search using three databases (PubMed, Embase, and ClinicalTrials.gov). Our search strategy included MeSH and keywords for breast cancer and SG including trade and generic names from the date of inception to January 15, 2022. Initial databases yielded 275 articles. After exclusion, two clinical trials on the use of SG in pretreated TNBC were included. Results: Among a total of 963 enrolled patients, 379 patients were evaluated. Majority of the patients received SG dose of 10 mg/kg. Bardia et al. studied the efficacy of SG in TNBC pts (n = 235) in phase III (ASCENT) trial achieved an overall response rate (ORR) of 31%. The median overall survival (OS) was 11.8 months (95% CI 10.5-13.8) and a median progression-free survival (PFS) was 4.8 months (95% CI, 4.1-5.8).Similarly, in another study Bardia et al. studied SG in TNBC pts (n = 144) in phase I/II (basket) trial and observed ORR of 33.3%. The median overall survival (OS) was 13 months (95% CI, 11.2 to 14) and a median progression-free survival (PFS) was 5.6 months (95% CI, 4.8 to 6.6). (Table) Diarrhea and Nausea was the most common adverse effect reported by the patient whereas neutropenia was the most common grade 3 adverse effect. Conclusions: SC showed promising outcomes in terms of ORR for the treatment of TNBC. [Table: see text] [Table: see text]
Humoral and cell-mediated immune response to the third dose of BNT162b2 anti-SARS-CoV-2 vaccine in patients with cancer on active treatment: Focus on wild type, Delta and Omicron strains.
Authors: Lasagna Angioletta , Cassaniti Irene , Bergami Federica , Lilleri Daniele , Percivalle Elena , Quaccini Mattia , Alessio Niccolò , Comolli Giuditta , Sarasini Antonella , Camilla Josè , Ferrari Alessandro , Arena Francesca , Secondino Simona , Cicognini Daniela , Schiavo Roberta , Lo Cascio Giuliana , Cavanna Luigi , Baldanti Fausto , Pedrazzoli Paolo
Published: June 2022

e13505

Background: Although a full course of COVID-19 vaccine is effective in cancer patients, the duration of the protection and the efficacy of a booster dose against the new variants remain unknown. We prospectively evaluated the immunogenicity of the third dose of the SARS-CoV-2 BNT162b2 mRNA vaccine in cancer patients undergoing active treatment. Methods: Patients with solid cancer, vaccinated with a booster dose during active treatment, were prospectively enrolled in this study. Patients were classified in SARS-CoV-2 naïve (without previous COVID-19 infection) and SARS-CoV-2 experienced (with previous COVID-19 infection). Neutralizing antibody (NT Abs) titer and total anti-Spike IgG concentration were quantified in serum. Heparinized whole blood samples were used for SARS-CoV-2 Interferon Gamma Release Assay (IGRA). The primary endpoint was to assess the increase of IgG antibody level between baseline (T0) and 3 weeks after the booster (T1). Results: 142 consecutive patients were recruited. In SARS-CoV-2 naïve subjects, median level of IgG was 157 BAU/mL (interquartile range (IQR) 62-423) at T0 and reached median of 2080 (IQR 2080-2080) at three weeks after booster administration (T1; p < 0.0001). A median 16-fold increase of SARS-CoV-2 NT Abs titre (IQR 4-32) was observed in naïve subjects (from median 20 IQR 10-40 to median 640 IQR 160-640; p < 0.0001). Median IFN-γ level at T1 was significantly higher than that measured at T0 in SARS-CoV-2 naïve subjects (p = 0.0049) but not in SARS-CoV-2 experienced patients. No difference was observed in terms of median response between patients treated with immunotherapy and chemotherapy (p > 0.05). A stronger correlation between SARS-CoV-2 NT Abs and total IgG level was observed at T0 (r = 0.76; p < 0.0001) compared to T1 (r = 0.27, p = 0.0081). No correlation as regards the number of days was observed from the first to the third vaccination and SARS-CoV-2 NT Abs/total IgG. The median level of SARS-CoV-2 NT Abs was 32-fold lower against Omicron compared to wild type strain (p = 0.0004) and 12-fold lower compared to Delta strain (p = 0.0110). Conclusions: The third dose is able to trigger both the humoral and the cell-mediated immune response in cancer patients on active treatment. Our preliminary data about the neutralization of the SARS-CoV-2 vaccine against variants of concern (VOCs) seem to confirm the vaccine lower activity.
Optimizing a team approach for successful accrual to and conduct of clinical trials in a community oncology practice.
Authors: Braun-Inglis Christa M , Agonoy Janela , Fukui Jami Aya
Published: June 2022

e13524

Background: Oncologists and advanced practice providers (APPs) routinely work as part of a team to provide quality cancer care in today’s healthcare environment. However, this does not always translate into the realm of clinical research. It is estimated that only 2-8% of the adult oncology population enrolls in a clinical trial, with more than 20% of current trials failing to meet accrual goals. These numbers are projected to be even worse due to the impact of the COVID pandemic. Our Oncologist/APP team in conjunction with a clinical research coordinator (CRC) set out to develop a workflow to approach and offer clinical trials to patients in our practice with the goal of increasing clinical trial accrual and improving clinical trial conduct. Methods: Between 1/1/19-12/31/21, a community breast oncology focused practice in the Hawaii M/U NCORP implemented a plan with the goal to increase accrual to clinical trials. Building on the prior experience of both clinicians, the practice developed a comprehensive team approach between the Oncologist, APP, and CRC. This approach included four components: 1) Clinic workflow for clinical trial screening, introduction, and follow-up of potential participants; 2) Shared clinical trial visits between MD & APP; 3) Protocol reviews by MD who reviewed treatment protocols & APP who reviewed symptom management and cancer care delivery research (CCDR) protocols. All clinical trial reviews were discussed with CRC for coordination input; 4) Protocol leadership between MD serving as local primary investigator (PI) on treatment trials, APP serving as local PI and/or site champion on symptom management and CCDR protocols. Results: From 2019-2021, our practice was able to accrue over 23% of our patients to clinical trials in a community practice setting, despite the COVID-19 Pandemic. Of the 149 unique accruals during this period, 59% of accruals were interventional trials and 41% were observational trials. Clinical trial accrual was racially diverse and mirrored the patient population. During this period, there were minimal protocol deviations observed based on review of shadow charts on this group of clinical trial patients. Conclusions: Through this team approach, our practice has been successful in having a high rate of clinical trial accrual while maintaining excellent clinical trial conduct even during the pandemic. We believe our team approach that utilizes the APP to the full scope of practice along with CRC empowerment in addition to the engaged oncologist is key to our success. Oncology practices and healthcare systems must value and engage all potential members of the team to maximize their clinical trial ability and to continue to offer/enroll patients in clinical trials as the standard of care.
Thromboprophylaxis in lung cancer patients with tinzaparin: Results from the investigation on cancer & lung thromboprophylaxis—The iCaLTstudy.
Authors: Kouvela Marousa , Grammoustianou Maria , Sarropoulou Foteini , Mani Maria , Gkiozos Ioannis , Syrigos Kostas N.
Published: June 2022

e13531

Background: It is known that malignancies exaggerate the risk of thrombosis up to 20%, while for Lung Cancer (LC) is articulated up to 14%. Likewise, thrombosis amplifies the LC progression, thrombosis-associated lung cancer (TALC). The pathophysiology promoting LCAT & TALC is multifactorial depending on the characteristics of LC, specific anti-cancer modalities, patient features, and biomarkers such as tissue factor, neutrophil extracellular traps released in response to cancer, cancer procoagulant, and cytokines. Low-molecular-weight heparins are used in prophylaxis and treatment for high-burden for thrombosis (HTB) patients, allowing specialists to focus on the cancer disease. Methods: iCaLT is a prospective observational study conducted in Thoracic Diseases General Hospital Sotiria (Athens, Greece) assessing the role of thromboprophylaxis with tinzaparin 10.000 Anti-Xa IU, OD with the systemic anti-cancer therapy (SACT). LC patients with active disease that are currently under treatment are enrolled after signing informed consent and monitored up to six months or until anticoagulation terminates. Results: Results from 106 patients reported, 29 (27%) are still ongoing: 79% were males. Histological results involve: adenocarcinomas 54%, squamous 25%, small cell 15%and others. LC patients received SACT: 55%, 23%, 10%, 6% in 1st, 2nd, 3rdand 4th line. HTB patients with active LC related to 4 factors: disease, treatment, biomarker and patient features are presented in table. On average patients accumulated 3.7±1.1risk factors, 91% of patients accumulated ≥3 risk factors. Median thromboprophylaxis duration was: 4.8 months (1st-3rd quartile: 2.8-6.0 months). One patient experienced thrombotic event in lower extremes and consequently pulmonary embolism (efficacy 99.1%, 95%CI: 94.6-99.8%), five patients experienced minor bleeding adverse events (haemoptysis) (4.7%, 95%CI: 2.0-10.6%), and two patients allergic reactions. Patients with haemoptysis had lower age (60 vs. 67, p=0.1357). Conclusions: Thromboprophylaxis with tinzaparin intermediate dose in high thrombotic burden patients with active lung cancer is effective and safe. Further research is needed.[Table: see text]
Impact of immunotherapy best practice alert on physician awareness of immune-related adverse events and patient outcomes in the urgent and emergent care setting.
Authors: Sassic Jessica , Ebrahimi Aren , Bollin Kathryn Blount
Published: June 2022

e13540

Background: Immune checkpoint inhibitors (ICI) are used to treat a wide range of malignancies and can provoke inflammatory side effects in any organ system. These immune-related adverse events (irAEs) are graded in severity according to the Common Terminology Criteria for Adverse Events (CTCAE) which serves as the basis for strategic toxicity management. Cancer patients treated with ICIs often present to urgent care (UC) and emergency room (ER) settings for CTCAE grade 2-4 irAEs. Providers in these settings need to recognize these irAEs as the treatment differs from chemotherapy toxicity management. Best practice alerts (BPAs) have been integrated in the electronic health record (EHR) to raise provider awareness to patients’ unique risk factors and improve patient outcomes. For example, a BPA for patients prescribed second generation antipsychotics led to more in-hospital providers ordering the appropriate laboratory studies to screen for metabolic derangements. Here, we describe our retrospective institutional protocol for the assessment of provider awareness and patient outcomes prior to and after the implementation of a BPA for patients receiving ICIs and presenting to an UC or ER with symptoms attributable to irAEs. Methods: Our institution will implement a BPA that identifies patients treated with ICIs within 6 months of presentation to an institutional UC or ER. The BPA will require providers to check a yes/no box asking if they considered an irAE in the differential diagnosis for the patient’s presenting symptom prior to advancing in the EHR. The BPA will include a hyperlink to the current American Society of Clinical Oncology guidelines for management of irAEs. After BPA implementation we will retrospectively analyze the EHR of patients treated with ICIs who presented to an institutional UC or ER for the time periods of 6-months prior to and after the implementation of the BPA. Our analysis will include review of the UC/ER providers’ differential diagnoses, imaging and laboratory studies, subspecialty consultations, and treatments provided. Our primary endpoint will be the quantification of patients diagnosed with an irAE at presentation both prior to and after implementation of the BPA. The secondary endpoints will include quantification of patients who received guideline-based management of irAEs in the UC/ER setting, time to resolution of symptoms to CTCAE grade 1 or less, and analysis of subspecialist involvement in the management of an identified irAE. We plan to use the Chi-squared method to observe for statistical significance of endpoints between the pre- and post- periods of BPA implementation. Our aim is to demonstrate the utility of a BPA in promoting the appropriate assessment and management of irAEs in cancer patients receiving checkpoint immunotherapies.
The adoption of relugolix for treatment of prostate cancer (PCa) in a large community medical oncology practice.
Authors: Schuster Victoria , Patel Dipen , Barnes Martin Christopher , Cyriac George , Staszewski Harry
Published: June 2022

e13541

Background: Relugolix was approved by the FDA in late 2020 as an oral gonadotropin-releasing hormone (GnRH) receptor antagonist for the treatment of adults with advanced PCa. The approval was based on a large randomized trial (Shore et al NEJM) of patients with evidence of biochemical or clinical relapse after local primary intervention with curative intent (50%), newly diagnosed mCSPCa (23%), and advanced localized disease not suitable for primary surgical intervention with curative intent (28%). Our study aims to observe the adoption of relugolix in a large community-based medical oncology practice with affiliated urologists. Methods: A retrospective study using our EMR identified 39 males with PCa for whom relugolix was initiated between January 2021 and December 2021. The charts were analyzed for demographics, indications for treatment, barriers encountered to initiation of treatment, duration of therapy, previous therapies, specialty, primary insurance, and cardiovascular history. Results: Thirty-nine (39) patients with either localized PCa (40%) or with metastases to lymph nodes or distant sites (51%) were recommended initiation of relugolix by either urology (26%) or oncology (74%). Of these, 77% actually started the medication. 9 patients did not start therapy, of which 3 were due to insurance denial, 1 due to death, 2 changed their mind, and 3 did not start for unclear reasons. Medicare covered 56% of the patients. Cardiovascular disease was notable in 87%. 28% switched from another ADT due to intolerance, 10% started relugolix due to progressive disease, and 33% started as initial ADT. 13% discontinued within 6 months. Of these, 1 completed planned therapy, 3 were intolerant, 1 was switched to alternate therapy due to progression, and 1 had complications due to COVID. In comparison, 689 patients initiated ADT with leuprolide over the same time. Conclusions: ADT using GnRH agonists or antagonists form the backbone of PCa treatment, typically given as injections. The HERO trial showed that relugolix, a newer oral therapy, is associated with lower rates of cardiovascular events compared to leuprolide. While having at least one cardiovascular risk factor is a consideration for patients to either start with or switch to relugolix, the large majority of our patients still received first-line therapy with leuprolide. This study demonstrates limitations to initiating relugolix including financial constraints (e.g., insurance coverage), patient preference, and medication intolerance.[Table: see text]
Automatic identification of oncology patients with unsupervised phenotyping and AutoML.
Authors: Zhang Jingqing , Sharma Atri Vivek , Bolanos Trujillo Luis , Gupta Vibhor , Guo Yike
Published: June 2022

e13547

Background: Recent studies suggest ICD codes often cannot characterise patients with specific diseases like oncology accurately in real-world clinical practice due to a high probability of miscoding, while manual inspection of millions of patients is not feasible as it is highly costly and slow. Therefore, we present an AI driven workflow, which leverages structured discrete values and unstructured textual data from Electronic Health Records (EHRs), to automatically identify cancer patients especially those who might be miscoded or undiagnosed. Methods: The proposed AI driven workflow is trained on 29637 and tested on 29339 patients from MIMIC-III database. First, the workflow builds patient profiles by leveraging the state-of-the-art unsupervised Natural Language Processing (NLP) method to extract phenotypic features from textual discharge summaries. Second, the workflow classifies if a patient has the risk of ovarian cancer (ICD-9: 183.0) or lung cancer (ICD-9: all subcodes of 162) based on their profiles using an Automated Machine Learning (AutoML) framework. Third, we improve the workflow through 100 gold-labelled patients out of the train set who are labelled as positive and negative ovarian (lung) cancer cases by three clinicians with consensus and we subsequently measure its performance against another 100 gold-labelled patients out of the test set and the entire test set with 29339 patients. Results: For ovarian cancer, on the 100 gold-labelled patients (52 ovarian cancer cases) out of the test set, the workflow achieves 0.877 AUCROC with precision 84.7% and sensitivity 96.2% whereas ICD codes have precision 94.6% and sensitivity 74.1%. On the entire test set with 29339 patients, the workflow identifies 111 ovarian cancer patients while ICD codes find only 38 patients which lead to 192% lifting. Similarly, for lung cancer, on the 100 gold-labelled patients (66 lung cancer cases) out of the test set, the workflow achieves 0.814 AUCROC with precision 88.7% and sensitivity 83.3% while ICD codes have precision 96.0% and sensitivity 72.7%. On the entire test set with 29399 patients, the workflow identifies 926 lung cancer patients while ICD codes find 585 patients which lead to 58% lifting. Conclusions: This study shows the AI driven workflow on textual clinical notes can help find more cancer patients with high accuracy especially those who are miscoded and undiagnosed by ICD codes. Since ICD codes are primarily used for billing purposes, this workflow also shows the opportunity to reconcile patient characteristics with ICD codes through the application of such novel AI at scale. Moreover, the results of this study have shown this approach can be scaled across other disease areas within oncology and beyond to help find new intelligence to characterise hard to diagnose conditions and improve patient outcomes through a significant improvement in speed and accuracy of screening and early diagnosis of patients.