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Prabhsimranjot Singh,1,2 Sudhamshi Toom,3 Akshay Avula,4 Vivek Kumar,2 Osama E Rahma1,2 1Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; 2Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA; 3Hematology and Oncology, Maimonides Medical Center, Brooklyn, NY, USA; 4Pulmonary and Critical Care, Staten Island University Hospital, Staten Island, NY, USACorrespondence: Prabhsimranjot Singh Email Prabhsimranjot_singh@dfci.harvard.eduAbstract: Locoregional therapies (LRTs) including radiofrequency ablation, surgical resection, and TACE, play a pivotal role in the treatment of early stage/locally advanced hepatocellular carcinoma (HCC). Besides their direct effect on tumor cells, LRTs also play an essential role in the immunomodulation of the tumor microenvironment which is of interest in the current era of cancer immunotherapy. In this review, we describe the HCC immune microenvironment and how it is affected by LRTs as described in multiple pre-clinical and clinical studies and provide the rationale for combining LRTs with immunotherapy.Keywords: hepatocellular carcinoma, immunotherapy, locoregional therapies

BACKGROUND Secretory breast carcinoma (SBC), an extremely rare malignancy, is related to a chromosomal translocation which leads to an ETV6-NTRK3 fusion mutation. SBC is characterized by eosinophilic secretions and is usually triple-negative, with a small number of patients demonstrating ER-positivity of the tumors. Diagnosis can be challenging and requires genomic testing for confirmation. CASE REPORT A 40-year-old woman presented with a breast mass found on mammography. She underwent an ultrasound-guided biopsy of the tumor. Initial pathology evaluation revealed features consistent with invasive ductal carcinoma. The immunochemistry report described an ER-positive, PR-negative, and HER2-negative tumor. The specimen was sent for oncotype scoring, which was not performed due to the specimen not meeting the criteria for invasive ductal carcinoma and displaying pathological features of SBC. A fluorescent in situ hybridization (FISH) study revealed ETV6 translocation, consistent with the diagnosis of SBC. The patient underwent lumpectomy followed by adjuvant radiotherapy and endocrine therapy. She remains in complete remission 3 years after treatment. CONCLUSIONS Accurately diagnosing SBC is of extreme importance as it has an indolent clinical course, but has a favorable prognosis if detected early. Due to nonspecific imaging findings, pathology evaluation with immunohistochemical staining followed by genomic testing is required. Our case highlights the challenges associated with SBC diagnosis requiring genomic testing due to equivocal pathological findings, along with increasing incidence of SBT in adults. There are no established guidelines for SBC management. The mainstay of treatment is partial or total mastectomy. Data on the benefits of adjuvant endocrine therapy, chemotherapy, and radiotherapy are inconclusive.

Background: Cancer patients may carry a worse prognosis with SARS-CoV-2 infection. Most of the previous studies described the outcomes of hospitalized cancer patients. We aimed to study the clinical factors differentiating patients requiring hospital care vs. home recovery, and the trajectory of their anti-cancer treatment. Methods: This study was conducted in a community cancer center in New York City. Eligible patients were those who had cancer history and were diagnosed of SARS-CoV-2 infection between March 1 and May 30, 2020, with confirmatory SARs-CoV-2 virus test or antibody test. Four groups were constructed: (A) hospitalized and survived, (B) hospitalized requiring intubation and/or deceased, (C) non-hospitalized, asymptomatic, with suspicious CT image findings, close exposure, or positive antibody test, and (D) non-hospitalized and symptomatic. Results: One hundred and six patients were included in the analysis. Thirty-five patients (33.0%) required hospitalization and 13 (12.3%) died. Thirty (28.3%) patients were asymptomatic and 41 (38.7%) were symptomatic and recovered at home. Comparing to patients who recovered at home, hospitalized patients were composed of older patients (median age 71 vs. 63 years old, p = 0.000299), more who received negative impact treatment (62.9 vs. 32.4%, p = 0.0036) that mostly represented myelosuppressive chemotherapy (45.7 vs. 23.9%, p = 0.0275), and more patients with poorer baseline performance status (PS ≥ 2 25.7 vs. 2.8%, p = 0.0007). Hypoxemia (35% in group A vs. 73.3% in group B, p = 0.0271) at presentation was significant to predict mortality in hospitalized patients. The median cumulative hospital stay for discharged patients was 16 days (range 5-60). The median duration of persistent positivity of SARS-CoV-2 RNA was 28 days (range 10-86). About 52.9% of patients who survived hospitalization and required anti-cancer treatment reinitiated therapy. Ninety-two percent of the asymptomatic patients and 51.7% of the symptomatic patients who recovered at home continued treatment on schedule and almost all reinitiated treatment after recovery. Conclusions: Cancer patients may have a more severe status of SARS-CoV-2 infection after receiving myelosuppressive chemotherapy. Avoidance should be considered in older patients with poor performance status. More than two thirds of patients exhibit minimal to moderate symptoms, and many of them can continue or restart their anti-cancer treatment upon recovery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lin, Wu, Toom, Sheth, Becker, Burdette-Radoux, D'Silva, Huang, Lipshitz, Meghal, Mo, Murthy, Rubin, Natarajan, Donahue and Xu.)

Introduction While coronavirus disease 2019 (COVID-19) mostly causes respiratory illnesses, emerging evidence has shown that patients with severe COVID-19 can develop complications like venous thromboembolism (VTE) and arterial thrombosis as well. The incidence of thrombosis among critically ill patients in the literature has been highly variable, ranging from 25 to 69%. Similarly, reported mortality among critically ill patients has been highly variable too, and it has ranged from 30 to 97%. In this study, we analyzed data from a large database to address the incidence, the risk factors leading to thrombotic complications, and mortality rates among COVID-19 patients. Material and methods Data were obtained from TriNetX (TriNetX, Inc., Cambridge, MA), a multinational clinical research platform that collects medical records from 42 healthcare organizations (HCOs). All nominal data were compared using the chi-squared test. Alpha of <0.05 was considered statistically significant. We used Benjamini-Hochberg correction with a false discovery rate of 0.1 to correct for multiple comparisons. Results We identified 18,652 COVID-19-positive patients, with a median age of 50.7 years [interquartile range (IQR): 31.8-69.6]; among them, 51.8% (9,672) were males and 48.2% (8,951) were females. Of these patients, 630 [3.37%; median age: 61 years (IQR: 44.9-77.1)] were critically ill, requiring intensive care unit (ICU) care within one month of their diagnosis. Men were over-represented among the ICU patients when compared to women (3.7% vs 3%, p=0.009, Χ 2 =6.66). African Americans were over-represented among the ICU patients when compared to Caucasians (8.5% vs 4%, p<0.0001, Χ 2 =76.65). Older patients, i.e., 65 years and older, were over-represented in the ICU compared to patients aged 18-64 years (6.8% vs 2.5%, p<0.0001, Χ 2 =121.43). The cumulative incidence of thrombotic events in the ICU population was 20.4% (129/630). Thrombotic events were significantly more common in patients who were 65 years and older when compared to patients in the age group of 18-64 years (24.6% vs 17.31%, p=0.02, Χ 2 =5.38). Mortality among ICU patients was higher in those who were 65 years and older when compared to the age group of 18-64 years (31.9% vs 17.3% p=0.0003, Χ 2 =18.41). The overall mortality in the study population was higher in patients who were 65 years and older when compared to patients aged 18-64 years (18.55% vs 1.4%, p<0.0001, Χ 2 =1915). Conclusions Among COVID-19 patients, men, African Americans, and people who are 65 years and older are more likely to have severe disease and require ICU level of care. Patients who are 65 years and older are more likely to have thrombotic events, myocardial infarction (MI), and stroke. Overall mortality and ICU mortality are higher among COVID-19 patients who are 65 years and older., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Avula et al.)

Objective: Acute stroke remains a medical emergency even during the COVID-19 pandemic. Most patients with COVID-19 infection present with constitutional and respiratory symptoms; while others present with atypical gastrointestinal, cardiovascular, or neurological manifestations. Here we present a series of four patients with COVID-19 that presented with acute stroke., Methods: We searched the hospital databases for patients that presented with acute stroke and concomitant features of suspected COVID-19 infection. All patients who had radiographic evidence of stroke and PCR-confirmed COVID-19 infection were included in the study. Patients admitted to the hospital with PCR- confirmed COVID-19 disease whose hospital course was complicated with acute stroke while inpatient were excluded from the study. Retrospective patient data were obtained from electronic medical records. Informed consent was obtained., Results: We identified four patients who presented with radiographic confirmation of acute stroke and PCR-confirmed SARS-CoV-2 infection. We elucidate the clinical characteristics, imaging findings, and the clinical course., Conclusions: Timely assessment and hyperacute treatment is the key to minimize mortality and morbidity of patients with acute stroke. Stroke teams should be wary of the fact that COVID-19 patients can present with cerebrovascular accidents and should dawn appropriate personal protective equipment in every suspected patient. Further studies are urgently needed to improve current understandings of neurological pathology in the setting of COVID-19 infection., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Targeted therapy and immunotherapy have revolutionized treatment of various cancers in the past decade. Despite targeted therapy with trastuzumab in Her2-positive gastric cancer patients, survival has been dismal, mostly due to disease progression and toxicity related to the treatments. One area of active development is looking for ideal monoclonal antibodies (IMAB) specific to the proteins only on the tumor and hence avoiding unnecessary side effects. Claudin proteins with isoform 2 are one such protein, specific for several cancers, particularly gastric cancer and its metastases, leading to the development of anti-claudin 18.2 specific antibody, claudiximab. This review will highlight the latest development of claudiximab as first in class IMAB for the treatment of gastric cancer.