3093 Background: Triple-negative breast cancer (TNBC) is a highly immunogenic disease and exhibits among the highest levels of immune infiltration compared with other breast cancer subtypes. These characteristics, coupled with the lack of effective targeted therapies, have made TNBC a key candidate for immunotherapy in selected clinical settings. While chemotherapy remains a mainstay of treatment, its immunomodulatory effects on the tumor immune microenvironment (TIME) remain poorly understood. This study computationally models immune cell to immune cell communication using Single-cell RNA sequencing data to identify immune driver cells and their interactions, and how they are altered by chemotherapy in TNBC. Methods: Single-cell RNA sequencing data of over 200,000 tumor cells from TNBC patients’ tumor samples were obtained from the Gene Expression Omnibus database. They were analyzed to comprehensively characterize the TIME before and after chemotherapy. We also considered healthy breast tissue to establish immune pathways unique to TNBC pathogenesis. We employed unsupervised clustering analysis, reciprocal principal component analysis with annotation from the NIH Center of Immunology for immune cell identifiers. Communication probability, interaction strength, and pathway information flow were computed, and differential signaling was evaluated using Wilcoxon rank-sum tests ( p < 0.05). Multiple hypothesis testing was also accounted for by Bonferroni-adjusted p-values to control false positives. Results: Immune activity within the TIME was minimal in healthy breast tissue, highlighting signaling pathways specific to TNBC pathogenesis. In contrast, there was an increased immune response in tumors after chemotherapy. Pathways with the highest communication activity included MHC-I/II, CCL, MIF, and CD99 signaling. Notably, CD86 signaling, which correlates with PD-L1 expression, and CD45 signaling were significantly activated after chemotherapy in TNBC. Additionally, CD23 signaling, associated with antitumor immunity, was enhanced following chemotherapy. Natural killer cells emerged as the key immune cell type mediating outgoing signals through annexin, IL16, CX3C, and CD99 pathways, which were largely inactive before treatment. Conclusions: Our findings demonstrate that chemotherapy reprograms the TIME in TNBC by enhancing intercellular communication among immune cells and upregulating pro-immune signaling pathways. This remodeling of the TIME suggests potential targets for novel immunotherapeutic discoveries and immune-checkpoint modulation in TNBC.

Cardiotoxicity from chemotherapy regimens has been long reported. However, the understanding of cardiac side effects of biological therapies is rapidly evolving. With cancer patients achieving higher life expectancy due to the use of personalized medicine and novel targeted anticancer agents, the occurrence of cardiotoxicity is becoming more significant. Novel biological therapies include anti-HER2 antibodies, tyrosine kinase inhibitors, bruton kinase inhibitors, antivascular endothelial growth factors, proteasome inhibitors, immunomodulator drugs, and immune checkpoint inhibitors. Potential cardiovascular toxicities linked to these anticancer agents include hypertension, arrhythmias, QT prolongation, myocardial ischemia and infarction, left ventricular dysfunction, congestive heart failure, and thromboembolism. Cardiac biomarkers, electrocardiography, echocardiography and magnetic resonance imaging are common diagnostic modalities used for early detection of these complications and timely intervention. This review discusses the various types of cardiotoxicities caused by novel anticancer biologic agents, their molecular and pathophysiological mechanisms, risk factors, and diagnostic and management strategies that can be used to prevent, minimize, and treat them.

Nuclear carcinoma of the testis (NUT) midline carcinoma are rare, poorly differentiated tumors resulting from t(15; 19) rearrangement, clinically characterized by aggressive and rapid progression to death. No optimal treatment regimen has been established for this rare malignancy. Surgery, chemotherapy, and radiation have been used for treatment alone or in combination, depending on location and staging of the disease, and may confer short periods of remission; however, re-emergence of the disease inevitably occurs. Targeted therapies such as bromodomain and extra-terminal domain protein (BET) inhibitors are currently in early phases of clinical trials. Here we describe a 49-year-old-male with no comorbidities who presented with acute worsening of chronic cough, new onset hemoptysis and left sided chest pain for 2 weeks. Workup revealed stage IIIB NUT midline carcinoma (NMC) of the lung with next-generation sequencing confirming the presence of a NUTM1-BRD4 fusion. The tumor was unresectable, and he began concurrent chemoradiation with weekly carboplatin and paclitaxel for 5 weeks. The follow-up CT scan showed partial response, so maintenance was continued with durvalumab. Two months later, he presented with metastasis to the posterior muscle compartment of the left arm, which was treated with local radiotherapy. Four months later he developed progression of lung disease with multiple pulmonary nodules. Durvalumab was discontinued and he was prescribed the BET inhibitor molibresib, 120 mg daily. After nearly 3 months of treatment with molibresib, he presented with brain metastasis for which he had a craniotomy with tumor resection and gamma knife radiation to solitary metastatic lesions. He was then prescribed chemo-immunotherapy with carboplatin plus pemetrexed and pembrolizumab. After two cycles of treatment his disease progressed, and he succumbed to it. Total survival was 18 months. In conclusion, NUT midline lung carcinoma is a rare but aggressive malignancy and patients have limited treatment options especially in advanced stages. Few targeted therapies have shown promising results in early clinical trials but more treatment options are awaited.

HER2-positive breast cancer is an aggressive subtype of breast cancer with five-year survival rates of 30% for the advanced stage. The development of anti-HER2 treatments has led to a paradigm shift in the management and clinical outcomes of advanced HER2-positive breast cancer patients. The standard first-line treatment consists of taxane-based chemotherapy plus dual anti-HER2 therapies with trastuzumab and pertuzumab. The antibody–drug conjugate (ADC) ado-trastuzumab emtansine (T-DM1) has been a second-line therapeutic standard, but the second-line treatment approach is rapidly evolving. Given a substantial advantage of another ADC, Fam-trastuzumab deruxtecan (T-DXd), compared to T-DM1 in a recent randomized trial in the second-line setting, T-DXd is currently the preferred second-line option. Optimal third-line treatment strategies are still not established, and multiple approaches have been used including combinations based on capecitabine, trastuzumab, or both with oral anti-HER2 tyrosine kinase inhibitors. Tucatinib plus capecitabine and trastuzumab, lapatinib plus trastuzumab, neratinib or lapatinib plus capecitabine are some of the FDA approved combinations. Another newer agent approved for third- or later-line therapy in the metastatic setting is margetuximab, an Fc-engineered anti-HER2 monoclonal antibody, in combination with chemotherapy. Other novel agents currently under clinical trials are the drugs that indirectly target HER2, including immune cell cycle inhibitors, PI3K/mTOR inhibitors, and immunotherapy agents.

Background PD1/L1 inhibitors are approved by FDA as first-line therapy for patients with advanced urothelial carcinoma (aUC) who are cisplatin-ineligible with high tumor PD-L1 expression or are platinum-ineligible regardless of PD-L1 expression. However, the outcomes when employing PD1/L1 inhibitors for platinum-ineligible patients are unclear. This retrospective analysis evaluates the clinical outcomes of first-line PD1/L1 inhibitors in patients with aUC deemed to be platinum-ineligible. Methods Data were retrospectively collected from 8 academic institutions. The following criteria were used to define platinum ineligibility: creatinine clearance (CrCl) < 30 mL/min; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 3; CrCl 30 to 59 mL/min and ECOG PS 2; elderly and/or comorbidities. Patient characteristics, responses and treatment-related toxicities were identified. Survival curves were estimated by the Kaplan-Meier method. A Cox regression analysis was conducted to explore the association of baseline variables with response and survival. Results A total of 79 platinum-ineligible patients with aUC were eligible. Patients were treated with atezolizumab (51.9%), pembrolizumab (35.5%), nivolumab (8.9%), or durvalumab (3.8%). The objective response rate was 27.9%. The median overall survival was 45 weeks (95% confidence interval [CI], 32-80), and the median treatment failure-free survival was 16 weeks (95% CI, 9-18). Treatment-related toxicity of any grade and grade ≥ 3 was seen in 41.8% and 31.7% of patients, respectively. Anemia and liver metastasis were associated with worse survival. Conclusion The efficacy of first-line PD1/L1 inhibitors for platinum-ineligible patients with aUC in the real world appears comparable to those reported in trials of unselected cisplatin-ineligible patients, whereas grade ≥ 3 toxicities appear more common. Further validation is required including data based on PD-L1 status and other biomarkers. Platinum-ineligible patients with aUC warrant evaluation of novel, safe, and effective agents.

Celiac plexus block (CPB) has been widely used as a treatment option for chronic intractable abdominal pain resulting from intra-abdominal malignancies as well as benign conditions. Complications resulting from CPB have been long reported and include diarrhea, back pain, paraplegia, postural hypotension, pneumothorax, and local anesthesia toxicity. Diarrhea and postural hypotension are two most common complications with studies reporting incidences occurring in 44% to 60% and 10% to 52% of patients, respectively. Diarrhea is most often transient, resolving within 48 hours; however, literature reports cases in which diarrhea was chronic, debilitating, and in some instances life threatening. Persistent diarrhea proves difficult to treat. We report a case of a 76-year-old male with unresectable pancreatic adenocarcinoma who underwent computed tomography-guided CBP complicated by persistent diarrhea and fecal incontinence. After conventional antidiarrheal failed to improve the symptoms, octreotide proved to be beneficial and the patient reported significant improvement in symptoms.

Background Sickle cell disease (SCD) is an inherited disorder of red blood cell (RBC) caused by a mutation in the beta-globin gene resulting in abnormal hemoglobin known as hemoglobin S (HbS) or the sickle hemoglobin. Several clinical variants of SCD have been elucidated, all driven by two fundamental pathophysiologic processes: RBC hemolysis and intermittent vaso-occlusive vasculopathy resulting in tissue ischemia/infarction. These two processes underscore the many complications and eventual multi-organ damage that may develop in patients with the most severe types of SCD. Cardiopulmonary complications including heart failure, pulmonary hypertension and acute chest syndrome (ACS) are major drivers of morbidity and mortality among patients with SCD. With regards to ACS, patients often present with fever, cough and shortness of breath caused by vaso-occlusive crisis affecting the lungs. This is particular concerning in view of its similar features to symptomatic COVID-19 infection. Methods We retrospectively identified SCD patients with COVID-19 infection admitted to Beaumont hospitals in Michigan between March 1st 2020 and July 1st 2020. Data was abstracted using the ICD 10 code of U07. 1 for COVID-19, ICD 9 and 10 codes of 282.60 and D57 for sickle cell disease. We excluded patients with sickle cell trait. Data regarding the demographics, presentation, management and outcomes were abstracted. Results A total of eleven patients with sickle cell disease were identified as having a positive SARS-Cov19 polymerase chain reaction test (Table I). All were African American and predominantly female (64%) with a mean age of 44 (22-60) years and mean BMI of 30.2 kg/m2. Genotypes identified were HbSS in 5 (45%) patients, HbSC in 4 (36%), HbS/beta-thalassemia in 1 (9%) and HbS/alpha-thalassemia in 1 (9%). All of the patients had seen a haematologist since their diagnosis but none of the patients were on hydroxyurea, voxeloter, L-glutamine or crizanlizumab at admission. The predominant clinical presentation was fever, chest pain, chills, exertional shortness of breath and cough but this was not consistent across all patients. All the patients were managed with intravenous hydration, pain management as well as hydroxychloroquine/azithromycin per institutional guideline at that time. Three patients (cases 1-3) had recurrent visits to the hospital for similar symptoms and new bone pain crises. Case 1 had a pulmonary embolus which was evident on re-admission. Two patients (cases 3 and 10) succumbed to COVID-19. Two patients (cases 5 and 7) presented with bone pain crisis and no respiratory symptoms, but chest imaging was suggestive of COVID-19 infection necessitating treatment with antibiotics, possibly indicating that the virus can trigger vaso-occlusive crises without respiratory symptoms. Case 8 had a high Charlson comorbidity index and age over 60, had the lengthiest hospital stay complicated by renal failure and polyneuropathy, and was discharged to a long-term acute care facility: an outcome which is consistent with current data showing that the elderly and unfit patients are more likely to have a higher morbidity and mortality with COVID-19. Conclusion To date, there no compelling evidence to provide guidelines for the management of SCD patients with COVID-19. However, following existing recommendations in managing acute chest syndrome and those for COVID-19 symptomatic infection, is a good place to start. We continue to seek to improve management of these patients as new evidence of successful treatment emerges, and also encourage patients to participate in clinical trials. Disclosures No relevant conflicts of interest to declare.

Plasma cell leukemia is rare and could be life-threatening. Even rarer and equally life-threatening is cryoglobulinemia. Both of them occurring together paints a grim clinical picture. We present the case of a 63-year-old male with plasma cell leukemia complicated by cryoglobulinemia with skin lesions. The report briefly reviews the clinical and diagnostic characteristics of plasma cell leukemia and well as available treatment options. It also highlights the need to consider non-chemotherapy-based regimens and clinical trials in the care of plasma cell leukemia patients.

3593 Background: Doublet chemotherapy FOLFOX and FOLFIRI are standard for first‐line treatment of metastatic colorectal cancer (mCRC). Recently, use of triplet chemotherapy FOLFOXIRI has shown an increased anti-cancer activity but still there is uncertainty regarding first line backbone chemotherapy. Therefore, we conducted this metanalysis to determine the efficacy, safety and outcome of triplet vs doublet chemotherapy. Methods: The study protocol was published at PROSPERO (CRD42020166745) and prepared as per PRISMA guidelines. Total 10 studies were included, with sample size of 1536 participants in triplet arm and 1535 participants in doublet arm. The primary outcome is Response rate (RR) and secondary outcomes are Progression-free survival (PFS), Overall survival (OS), post chemotherapy radical (R0) surgical resection rate of metastases. Quantitative synthesis was performed using “R” statistical package. Dichotomous outcomes were summarized using odds ratio (OR) and time to event data was summarized using hazard ratio (HR). Results: A total of 678 articles were retrieved. The Medline article search gave a result of 271 article, Embase 296, the Cochrane Library 100 and Clinical tral.gov 11, when searched through April 2020. Total 10 studies were included. All the studies were randomized, open-label, multicenter study. Out of the 10 trials 5 each were phase II and phase III studies. The pooled odds ratio for RR was 1.66 (95% CI 1.42 to 1.93) and PFS was (HR, 0.70; 95% CI, 0.63–0.78) in favor of triplet chemotherapy. There was significant improvement in radical resection (R0) of metastases (OR 1.59; 95% CI, 1.27–1.98) in triplet arm. Triplet arm was also associated with increased toxicity especially neurological events 2.51(0.88-7.16), diarrhea 2.40(1.74-3.31), neutropenia, 2.23(1.71-2.90) and thrombocytopenia 1.94(1.05-3.59). Conclusions: Findings in this meta-analysis showed that FOLFOXIRI significantly improves the PFS, RR, OS, and R0 resection rate of overall metastases over the doublet chemotherapy. The incidence of fatal adverse events was found to be more in triplet chemotherapy compared to doublet therapy. Therefore, we concluded that with moderate evidence FOLFOXIRI provide clinically meaningful efficacy benefit at cost of increased toxicity.[Table: see text]

Background: Lung cancer is one of the leading causes of cancer mortality in the US. The use of precision medicine in the past 10 years has significantly changed the therapeutic landscape of lung cancer. Management of advanced non-small cell lung cancer (NSCLC) has transitioned from a chemotherapeutic approach to targeted treatments and immunotherapeutic agents. Several tyrosine kinase inhibitors (TKIs) have been approved for patients with targeted mutations while patients who do not have driver mutations; immunotherapy has been recently approved as frontline therapy, which has resulted in marked improvement in overall survival and added a new tool in our armamentarium. Aims: The purpose of this review is to highlight recent advancements in diagnostic approach and management strategies in patients with metastatic NSCLC. Materials and methods: Published studies included in Medline (via PubMed) and National Comprehensive Cancer Network Guidelines were reviewed for data gathering. Conclusion: The use of next generation sequencing has significantly changed our understanding of molecular oncogenic mechanisms of lung cancer. These advancements have created a paradigm shift in the treatment strategies of metastatic lung cancer from primarily chemotherapeutic approach to increasing use of targeted therapies and immune check point inhibitors (ICI) leading to better survival rates and lesser toxicity.

The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality worldwide. While patients with COVID-19 most frequently present with pneumonia, respiratory failure and acute respiratory distress syndrome, increasing cases of immune-mediated disorders such as autoimmune thrombocytopenia, haemolytic anaemia and antiphospholipid syndrome have been reported. In this article we describe a rare case of cold agglutinin syndrome (CAS) in a patient with COVID-19. The patient was a 77-year-old man with a history of glucose-6-phosphate dehydrogenase (G6PD) deficiency who presented with COVID-19 infection and acute respiratory failure. Initially he was started on intravenous steroids, antibiotics and hydroxychloroquine. Laboratory analysis revealed haemolytic anaemia with a positive direct anti-globulin test (DAT) and high titres of cold agglutinins. Hydroxychloroquine was stopped due to suspicion of haemolysis due to G6PD deficiency but the haemolysis persisted. Unfortunately, the respiratory failure progressed and the patient died. In summary, this article describes a rare case of CAS associated with COVID-19. CAS is a heterogenous group of cold autoimmune haemolytic anaemias occurring secondary to infections or malignancies. No definite treatment for CAS in COVID-19 patients has been approved so far.LEARNING POINTS:Autoimmune haemolytic anaemia has been reported in COVID-19 patients.Cold agglutinin syndrome (CAS) can occur in patients with COVID-19.Efforts to determine the optimal management of CAS in COVID-19 patients must continue.

We report a case of a 91-year-old Caucasian woman with a history of chronic lymphocytic leukaemia who developed acute hypoxic respiratory failure (AHRF) requiring intubation for less than 24 hours after receiving rasburicase. Laboratory workup was significant for methemoglobinemia and acute anaemia, and blood film demonstrated evidence of oxidative haemolysis with bite cells. The patient was given a presumptive diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency and was managed conservatively with successful resolution of AHRF and stabilisation of haemoglobin level. Seven days after admission, she passed away due to subsequent complications; hence, follow-up G6PD level could not be obtained. Haemolytic anaemia and methemoglobinemia in the setting of recent rasburicase administration should raise clinical suspicion for G6PD deficiency. In non-emergent cases, patients should be screened prior to receiving rasburicase regardless of risk factors. Because rasburicase is often needed emergently, patients at high risk of tumour lysis syndrome should be screened early for G6PD deficiency.

Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2. Primarily an infection of the lower respiratory tract, it is now well known to cause multisystem abnormalities. Hematologic manifestations constitute a significant area of concern. Severe acute respiratory syndrome coronavirus 2 infects monocytes and endothelial cells leading to a complex downstream cascade, cytokine storm, and eventual intravascular thrombosis. Coronavirus disease 2019 causes lymphopenia, neutrophilia, and thrombocytopenia. Prophylactic anticoagulation is vital in patients with coronavirus disease 2019, as its effect on the coagulation system is associated with significant morbidity and mortality. The disease can cause both arterial and venous thromboses, especially pulmonary embolism and pulmonary microthrombi. A high index of suspicion is indispensable in recognizing these complications, and timely institution of therapeutic anticoagulation is vital in treating them. Virus-induced disseminated intravascular coagulation is uncommon but shares some similarities to sepsis-induced disseminated intravascular coagulation. Marked elevations in hematologic biomarkers such as lactate dehydrogenase, D-dimer, ferritin, and C-reactive protein are associated with worse outcomes. Understanding the pathophysiology and recognizing factors associated with poor prognosis are crucial in improving patient outcomes with coronavirus disease 2019.

Objectives: Community-acquired pneumonia (CAP) is an important complication in patients with chronic obstructive pulmonary disease (COPD). This study aimed to define incidence, and outcomes of COPD patients hospitalized with pneumonia in the city of Louisville, and to estimate the burden of disease in the US population. Methods: This was a secondary analysis of a prospective population-based cohort study of residents in Louisville, Kentucky, 40 years old and older, from 1 June 2014 to 31 May 2016. All adults hospitalized with CAP were enrolled. The annual incidence of pneumonia in COPD patients in Louisville was calculated and the total number of adults with COPD hospitalized in the United States was estimated. Clinical outcomes included time to clinical stability (TCS), length of hospital stay (LOS) and mortality. Results: From a Louisville population of 18 246 patients with COPD, 3419 pneumonia hospitalizations were documented during the 2-year study. The annual incidence was 9369 patients with pneumonia per 100 000 COPD population, corresponding to an estimated 506 953 adults with COPD hospitalized due to pneumonia in the United States. The incidence of CAP in patients without COPD was 509 (95% CI 485 - 533) per 100 000. COPD patients had a median (interquartile range) TCS and LOS of 2 (1-4) and 5 (3-9) days respectively. The mortality of COPD patients during hospitalization, at 30 days, 6 months and 1 year was 193 of 3419 (5.6%), 400 of 3374 (11.9%), 816 of 3363 (24.3%) and 1104 of 3349 (33.0%), respectively. Conclusions: There was an annual incidence of 9369 cases of hospitalized CAP per 100 000 COPD patients in the city of Louisville. This was an approximately 18-fold greater incidence of CAP in COPD patients than in those without COPD. (C) 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

4576 Background: IO-VEGF combinations are the backbone for current and future therapeutic developments in RCC with several IO-VEGF regimens reporting positive results in phase 3 trials. However, limited data exists on outcomes to subsequent therapy in patients progressing on IO-VEGF regimens. Methods: A retrospective analysis was performed on patients with ccRCC at the Memorial Sloan Kettering Cancer Center and Cleveland Clinic Cancer Institute who initiated systemic therapy post IO-VEGF regimens including combinations with VEGFR tyrosine kinase inhibitors (IO-TKI) and combinations with anti-VEGF monoclonal antibodies (IO-mAB). Patients treated on unreported clinical trials were excluded from the outcomes analysis. The primary objective was to evaluate the overall survival (OS) post IO-VEGF. The secondary objectives included objective response rate (ORR) and progression-free survival (PFS) according to RECIST v1.1. Kaplan-Meier methods and the log-rank test were used to evaluate time from start of systemic therapy post IO-VEGF to the event of interest. Results: Fifty-nine patients were treated after discontinuation of IO-VEGF regimens. Prior IO-VEGF regimens included IO-mAB (n = 35, 59%) and IO-TKI (n = 24, 41%). IMDC scores at the start of next line of therapy were favorable in 20%, intermediate in 60% and poor in 20%. Next line of therapy included VEGFR-TKI monotherapy (n = 45, 76%), VEGFR-TKI based combinations (n = 6, 10%), mTOR inhibitors (n = 3, 5%), and unreported clinical trials (n = 5, 9%). VEGFR-TKI containing regimens (n = 51) included cabozantinib (n = 22), axitinib (n = 17), lenvatinib/everolimus (n = 4), pazopanib (n = 4), and others (n = 4). Median OS was 24.5 months (95% CI 12-NE) with a 12 months OS rate of 63%. The ORR was 27% (14/51) and the median PFS was 6.8 months (95% CI 4.8-11). No difference in post IO-VEGF OS was observed when comparing IO- TKI vs IO-mAB (log rank p = 0.7). Conclusions: Post combination IO-VEGF treatment, most patients received VEGFR-TKIs. In this setting, VEGFR-TKIs continue to show clinical activity similar to historic experiences of patients post VEGF monotherapy.

18 Background: Despite treatment with AA/P, many patients with mHSPC will develop castrate resistant disease (CRPC). Early recognition of progression is difficult. Changes in PSA patterns in patients with mHSPC treated with AA/P may help identify evolution to mCRPC. Methods: All patients with mHSPC who initiated ADT and AA/P from June 2017 to February 2019 at the Cleveland Clinic were eligible. Patterns of PSA change were evaluated using a longitudinal mixed model at time 0, 3, 6, 9, and 12 months (mo) from AA/P initiation. Time to PSA<0.03 and CRPC were estimated using Kaplan-Meier method. Progression was defined as a PSA rise at two consecutive time points. Results: Of the 143 patients who initiated AA/P, 134 men (median Gleason score 8, baseline PSA 15.0 ng/mL) with follow up were included. 52% had de novo mHSPC, 47.8% had prior therapy (21% surgery, 20% radiation, 7% both), and 16% had visceral disease. PSA levels dropped 98.2% in the first 3 mo (p<0.001), slowed from 3-9 mo (p<0.05) and plateaued after 9 mo. The % PSA reduction from time 0 to the other time points was small. The median time to PSA<0.03 was 11 mo. Of those who progressed to CRPC, the reduction within the first 3 mo was more significant than in those who did not (Table). Measurable PSA was higher in patients who progressed to CRPC at all-time points and plateaued by 6 mo. 12-mo CRPC-free after AA/P was 86.7% (95% CI: 79.2, 94.1). Patients with ≥ 98% 3-mo PSA reduction had better CRPC-free survival than patients with <98% reduction (12-mo CRPC-free: 94.4% vs 78.4%), p<0.001. Conclusions: The degree of PSA decline within 3 mo of AA/P may be used as treatment efficacy measurement. Tracking PSA pattern changes may alert clinicians for potential progression, consider frequent PSA and imaging, as well as initiate sequential therapy.[Table: see text]

Introduction The emergence of novel hormonal therapies and the increase availability of sensitive next-generation imaging techniques has significantly changed the management of recurrent prostate cancer. Areas covered In this review, we summarize the definition, diagnosis, treatment, and ongoing clinical trials in non-metastatic castration resistant prostate cancer (M0CRPC). We have also discussed the role of newer imaging modalities in the detection of advanced prostate cancer. Expert opinion M0CRPC is a disease state in prostate cancer when serologic progression (PSA only disease) occurs despite castrated levels of testosterone and imaging shows no evidence of metastasis. With the availability of next-generation imaging, more patients are migrating from M0CRPC to mCRPC space. This stage migration impacts the treatment options currently available in clinical practice and requires the integration of novel imaging in prospective studies moving forward. Until that data become available men with M0CRPC should be considered for therapy with any of these three novel oral AR inhibitors, with a positive impact in metastasis-free and overall survival. Treatment selection should be based on Quality of Life, side effects, and drug-drug interactions.

Hepatocellular carcinoma (HCC) is the most common primary liver tumor, and its incidence has been on the rise worldwide. It is a common cause of cancer-related death. HCC carries a poor prognosis and is challenging to manage, especially when diagnosed in advanced stages. We present a rare case of HCC in liver cirrhosis secondary to viral hepatitis C (HCV) infection, presenting with large tumor thrombus extending to the right atrium treated with lenvatinib.

Despite treatment with abiraterone acetate and prednisone (AA/P), most patients with metastatic hormone sensitive prostate cancer (mHSPC) will develop castration-resistant disease (metastatic castration-resistant prostate cancer [mCRPC]). The early identification of who will progress on AA/P is limited. This study investigates the role of prostate surface antigen (PSA) kinetics as a predictor of progression in mHSPC patients treated with AA/P. All patients with mHSPC who initiated androgen deprivation therapy (ADT) and AA/P from June 2017 to February 2019 at the Cleveland Clinic were eligible. PSA-mCRPC was defined as a PSA rise at two consecutive time points. Patients were followed until first mCRPC or last contact after AA/P. Patterns of PSA change were evaluated using a longitudinal mixed model at time 0, 3, 6, 9, and 12 months from AA/P initiation. The association between PSA profile at 3 months and PSA-mCRPC was examined using survival analysis. Radiographic progression (Rad-mCRPC) was also analyzed. A total of 130 men with follow-up were included. The median (interquartile range [IQR]) follow-up time was 15.3 (10.5, 22.5) months. Eighty-two percent were Caucasian (median age 68.5 years); participants had a median (IQR) PSA of 16.8 (5.3, 48.0) ng/mL. Half of the patients had de novo disease, and 46.2% had high-risk disease (61% had a Gleason score ≥ 8, 16% had visceral disease, and 54% had three or more bony lesions). The greatest PSA percentage reduction from baseline after AA/P initiation occurred at the first 3 months (median 98.3%). The reduction at 6–12 months from baseline was small (99.7–100%). Patients without PSA-mCRPC had a significantly greater 3-month reduction of PSA values compared to patients who developed PSA-mCRPC (p interaction = 0.0002). 50.8% of patients were able to achieve a non-detectable PSA (median 13.1 months). PSA-mCRPC (n = 20) was observed from 4 to 24 months after AA/P, with the majority of events occurring within the first 12 months. Patients with PSA < 0.3 ng/mL (12-month PSA-mCRPC–free 94.5% vs. 69.4%, p = 0.0004) or a ≥ 98% reduction (94.9% vs. 68.0%, p = 0.0002) at 3 months had better PSA-mCRPC–free survival compared to their counterparts. Absolute reduction at 3 months was not associated with PSA-mCRPC. Similar PSA patterns were seen in those who had Rad-mCRPC compared to no Rad-mCRPC (p interaction < 0.05). The degree of PSA decline at 3 months predicted serologic progression to mCRPC. Those who developed castration-resistant disease had higher PSA and a lower percentage reduction by 3 months. Tracking early PSA pattern changes may alert clinicians to poor treatment effect and potential progression; they should consider frequent PSA measurement and imaging, as well as the initiation of sequential therapy.