Ziad Bakouny

• MD, MSc
• Hematology oncology fellow at Memorial Sloan Kettering Cancer Center

Interleukin-8, produced by intratumoral and circulating myeloid cells, correlates with an immunosuppressive myeloid-enriched tumor microenvironment and adverse cancer prognosis.

Patients with cancer have been disproportionately affected by the COVID-19 pandemic. This effect has included the adverse outcomes in patients with cancer who develop COVID-19, the impact of the COVID-19 pandemic on the delivery of cancer care, and the severe disruption to cancer research. However, patients with cancer are a heterogeneous populatio...

Sarcomatoid and rhabdoid (S/R) renal cell carcinoma (RCC) are highly aggressive tumors with limited molecular and clinical characterization. Emerging evidence suggests immune checkpoint inhibitors (ICI) are particularly effective for these tumors, although the biological basis for this property is largely unknown. Here, we evaluate multiple clinica...

Translocation renal cell carcinoma (tRCC) is a poorly characterized subtype of kidney cancer driven by MiT/TFE gene fusions. Here, we define the landmarks of tRCC through an integrative analysis of 152 patients with tRCC identified across genomic, clinical trial, and retrospective cohorts. Most tRCCs harbor few somatic alterations apart from MiT/TF...

4542 Background: The impairment of oxidative phosphorylation (OxPhos) and upregulation of aerobic glycolysis, mediated by the loss of VHL , are key features of clear cell renal cell carcinoma (ccRCC). In contrast, non-clear cell renal cell carcinoma (RCC) denotes a heterogeneous group of tumors with few known nuclear oncogenic drivers. Recent studi...

9003 Background: IMGs constitute one-third of practicing oncologists in the US. However, there is limited data on their academic contributions. We analyzed the research productivity of IMG hematology-oncology fellows in US fellowship programs. Methods: Hematology-oncology fellows enrolled in an ACGME accredited training program as of June 2024, wer...

9009 Background: International Medical Graduates (IMGs) are a vital component of the US oncology workforce, representing nearly half of practicing medical oncologists. However, systemic barriers may influence their career trajectories differently. Understanding these challenges is essential for addressing workforce disparities and optimizing cancer...

9016 Background: Almost two-thirds of physicians report delaying childbearing due to medical training. Amongst hematologists-oncologists (HOs), up to 75% report burnout related to parenting. International Medical Graduates (IMGs) account for a third of all practicing HOs; yet little is known about the unique challenges they face in navigating paren...

4547 Background: KEAP1 is a tumor suppressor and negative regulator of the NRF2 pathway, and inactivating KEAP1 mutations (mts) have been reported in patients (pts) with RCC with similar morphology to fumarate hydratase (FH)-deficient RCC (FH-RCC). In FH-RCCs, the NRF2 pathway is activated through fumarate-led inactivation of KEAP1, and we hypothes...

9004 Background: Although IMGs comprise one-third of US oncologists, their leadership presence at academic centers with affiliated oncology fellowship training programs has not been studied. Methods: Using Electronic Residency Application Services website for training programs, and publicly available information on corresponding institutional websi...

1558 Background: Understanding why patients develop adverse events to anti-cancer therapies and predicting the occurrence of these toxicities has lagged behind tumor response biomarker development. This critical gap is primarily due to limited availability of large-scale curated toxicity data. Here, we leverage advances in natural language processi...

Introduction VHL loss is a cardinal feature of renal cell carcinoma (RCC), specifically of the clear cell RCC (ccRCC) subtype, and leads to activation of aerobic glycolysis and suppression of oxidative phosphorylation (OxPhos). In contrast, Non-VHL driven forms of RCC are a heterogeneous group of tumors with few known nuclear oncogenic drivers, non...

583 Background: ChRCC is a rare form of kidney cancer that has shown limited response to immune checkpoint inhibitors currently used as the standard-of-care for other RCC histologies. mTOR inhibition is a therapeutic strategy for advanced ChRCC, but the mechanistic basis for response remains poorly understood. We investigated clinical responses to...

Renal cell carcinoma (RCC) is characterized by recurrent somatic mutations in epigenetic regulators, which stratify patients into clinically significant subgroups with distinct prognoses and treatment responses. However, the cell type-specific epigenetic landscape of RCC—broadly and in the context of these mutations—is incompletely understood. To i...

Databases that link molecular data to clinical outcomes can inform precision cancer research into novel prognostic and predictive biomarkers. However, outside of clinical trials, cancer outcomes are typically recorded only in text form within electronic health records (EHRs). Artificial intelligence (AI) models have been trained to extract outcomes...

PURPOSE International medical graduates (IMGs) are an essential component of the oncology workforce in the United States, comprising a third of all practicing oncologists and almost half of hematology/oncology fellows. In this article, we discuss the contributions of IMGs in the US oncology workforce, review unique challenges faced by IMGs, and pro...

29 Background: International Medical Graduates (IMGs) comprise over one-third of internal medicine (IM) trainees and practicing oncologists in the United States. We aimed to examine challenges faced by IM IMG residents in pursuing hematology-oncology (HO) fellowship positions. Methods: We conducted a pilot survey using SurveyPluto to assess demogra...

Background The PARP inhibitor (PARPi) olaparib is approved for homologous recombination repair (HRR) gene‐altered metastatic castration‐resistant prostate cancer (mCRPC). However, there is significant heterogeneity in response to PARPi in patients with mCRPC. Better clinical biomarkers are needed to identify patients likely to benefit from PARPi....

9000 Background: Despite IMGs accounting for up to one-third of all practicing oncologists in the United States, little is known about their contributions to presentations at international oncology meetings, such as the American Society of Clinical Oncology (ASCO). Therefore, we investigated the representation of IMGs in invited faculty roles at AS...

Background and objective Previous germline studies on renal cell carcinoma (RCC) have usually pooled clear and non–clear cell RCCs and have not adequately accounted for population stratification, which might have led to an inaccurate estimation of genetic risk. Here, we aim to analyze the major germline drivers of RCC risk and clinically relevant b...

449 Background: Sarcomatoid differentiation (SD) in renal cell carcinoma (RCC) is associated with poor survival and heightened response to immune checkpoint blockade. Detection of SD can be challenging due to spatial heterogeneity and sampling error. Herein, we introduce a novel tissue–informed epigenomic approach to noninvasively identify sarcomat...

459 Background: While immune checkpoint inhibitors (ICI) have improved outcomes in patients (pts) with metastatic renal cell carcinoma (mRCC), acquired resistance (ARX) is commonly encountered. We aimed to characterize the genomic and transcriptomic correlates underlying ARX in ICI-treated mRCC patients. Methods: We identified pts with mRCC at Dana...

476 Background: ChRCC is a rare form of kidney cancer with a poor prognosis in the metastatic setting, in part due to very limited responses to immune checkpoint inhibitors (ICIs), as compared to clear cell RCC (ccRCC). The mechanisms underlying the poor response of ChRCC to ICIs remain largely uncharacterized. We therefore investigated at the sing...

Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are (1) a limited understanding of its gene regulatory programs and (2) difficulty identifying sarcomatoid differentiation on tumor biopsies d...

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed s...

Clear cell renal cell carcinoma (ccRCC) is molecularly heterogeneous, immune infiltrated, and selectively sensitive to immune checkpoint inhibition (ICI). However, the joint tumor-immune states that mediate ICI response remain elusive. We develop spatially aware deep-learning models of tumor and immune features to learn representations of ccRCC tum...

Background ChRCC is a rare form of kidney cancer and presents with a poor prognosis in the metastatic setting, with limited response to immune checkpoint inhibitors (ICI) and targeted therapy. While previous studies suggested that ChRCC originates from intercalated cells of the kidney, its exact cellular origin has not been clearly defined. We ther...

Background Renal cell carcinoma of variant histology (vRCC) encompasses approximately 20% of RCC diagnoses. Due to a poor understanding of the different biologies of vRCCs, there is currently no standard of care for this type of tumor and guidelines are extrapolated from clear-cell RCC trials. A phase II trial of atezolizumab plus bevacizumab in pa...

Background Sarcomatoid differentiation of RCC (sRCC) is associated with poor survival. Recent studies showed marked response of sRCC to immune checkpoint blockade (ICB). While distinctive patterns of gene expression in sRCC have been identified, the gene regulatory programs and TFs that drive SD remain unknown. The aim of this study is to nominate...

Background Treatment options for mRCC have evolved to include VEGF targeted therapies (VEGF-TT), immune checkpoint inhibitors (ICIs), or combinations of both. However, clinical responses to systemic therapies in mRCC remain largely unpredictable and robust biomarkers are still lacking. The interaction between the tumor and its immune microenvironme...

Femoro-acetabular impingement (FAI) may present as alterations in the skeletal morphology of the hip. Repercussions of FAI can be witnessed in self-selected speed walking as well as physical exercise such as running or fast speed walking. The aim of this study was to investigate changes in kinematics at different gait speeds in subjects presenting...

Introduction Sarcomatoid RCC (sRCC) is associated with poor prognosis. Recent studies showed promising response rates of sRCC to immune checkpoint blockade (ICB). Although distinct patterns of gene expression in sRCC have been reported, the gene regulatory programs that drive SD remain unknown. This study aims to nominate TFs driving SD and to eval...

Background: Chromophobe renal cell carcinoma (ChRCC) represents 5% of all kidney cancers. In contrast to clear cell RCC (ccRCC), the immune landscape of ChRCC and its response to immunotherapy remain poorly characterized. We sought to evaluate the clinical outcomes of patients with ChRCC treated with immuno-oncology (IO)-based regimens, and assess...

Patients with metastatic clear cell renal cell carcinoma (mccRCC) experience highly heterogeneous outcomes when treated with standard-of-care systemic regimens. Therefore, valid biomarkers are needed to predict the clinical response to these therapies and help guide management. In this review, the authors outline relevant and promising biomarkers f...

Immunotherapy has revolutionized treatment for patients with advanced and metastatic renal cell carcinoma. Nevertheless, many patients do not benefit or eventually relapse, highlighting the need for novel immune targets to overcome primary and acquired resistance. This review discusses 2 strategies currently being investigated: disabling inhibitory...

Targeted therapies have revolutionized the treatment of renal cell carcinoma (RCC). The VHL/HIF pathway is responsible for the regulation of oxygen homeostasis and is frequently altered in RCC. Targeting this pathway as well as the mTOR pathway have yielded remarkable advances in the treatment of RCC. Here, we review the most promising novel target...

Molecular routes to metastatic dissemination are critical determinants of aggressive cancers. Through in vivo CRISPR–Cas9 genome editing, we generated somatic mosaic genetically engineered models that faithfully recapitulate metastatic renal tumors. Disruption of 9p21 locus is an evolutionary driver to systemic disease through the rapid acquisition...

Renal cell carcinoma (RCC) of variant histology comprises approximately 20% of kidney cancer diagnoses, yet the optimal therapy for these patients and the factors that impact immunotherapy response remain largely unknown. To better understand the determinants of immunotherapy response in this population, we characterized blood- and tissue-based imm...

Background Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited. Objectives To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF. Methods Retrospective cohort...

4558 Background: ChRCC is an uncommon kidney cancer variant that has a poor prognosis in the metastatic setting, with limited response to current standard-of-care immune checkpoint inhibitors (ICIs) used for other RCC histologies. We evaluated the tumor-immune microenvironment of ChRCC and other related oncocytic neoplasms to better understand the...

4519 Background: Patients with advanced RCC with S/R components exhibit poor clinical outcomes. IO-based combination therapies demonstrated substantial efficacy among patients with metastatic S/R ccRCC, compared to VEGF targeted therapy (VEGF-TT). Recent trials showed promising activity of IO-based regimens in patients with advanced nccRCC. We soug...

4550 Background: Treatment options for mRCC have evolved to include VEGF targeted therapies (VEGF-TT), immune checkpoint inhibitors (ICIs), or combinations of both. The interaction between the tumor and its immune microenvironment has been shown to influence clinical outcomes in patients treated with immunotherapy-based regimens. The aim of this st...

4535 Background: The treatment of metastatic nccRCC remains an area of unmet clinical need. A multicenter phase II trial of atezolizumab/bevacizumab in patients with advanced nccRCC or any RCC type with ≥ 20% sarcomatoid differentiation (NCT02724878) demonstrated clinical activity of these agents, with objective response rates of 50% in patients wi...

Introduction: COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or imm...

Background Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed se...

654 Background: IO-based regimens have demonstrated substantial efficacy in the management of metastatic clear-cell RCC (mccRCC), where they currently represent the standard of care. ChRCC has a dismal prognosis in the metastatic setting. Recent clinical trials evaluating IO-based regimens across non-ccRCC subtypes identified a preliminary poor res...

Background: Breakthrough SARS-CoV-2 infections following vaccination against COVID-19 are of international concern. Patients with cancer have been observed to have worse outcomes associated with COVID-19 during the pandemic. We sought to evaluate the clinical characteristics and outcomes of patients with cancer who developed breakthrough SARS-CoV-...

Clear cell renal cell carcinoma (ccRCC) is molecularly heterogeneous, immune infiltrated, and selectively sensitive to immune checkpoint inhibition (ICI). Established histopathology paradigms like nuclear grade have baseline prognostic relevance for ccRCC, although whether existing or novel histologic features encode additional heterogeneous biolog...

IMPORTANCE RCC encompasses a set of histologically distinct cancers with a high estimated genetic heritability, of which only a portion is currently explained. Previous rare germline variant studies in RCC have usually pooled clear and non-clear cell RCCs and have not adequately accounted for population stratification that may significantly impact...

Background There remains a paucity of data regarding the efficacy of immune checkpoint therapy (ICT) combinations ± vascular endothelial growth factor (VEGF) targeted therapy (TT) in translocation renal cell carcinoma (tRCC). Methods This is a retrospective study of patients with advanced tRCC treated with ICT combinations at 11 centers in the US,...

Immune checkpoint inhibitors (ICIs) have yielded remarkable responses but often lead to immune-related adverse events (irAEs). Although germline causes for irAEs have been hypothesized, no individual variant associated with developing irAEs has been identified. We carried out a genome-wide association study of 1,751 patients on ICIs across 12 cance...

Importance Cytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation. Objective To determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with ca...

Background The role of upfront cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) in the era of immune checkpoint inhibitors is unclear. Objective To evaluate the relationship between upfront CN and clinical outcomes in the setting of mRCC treated with immune checkpoint inhibitors or targeted therapy. Design, setting, and p...

Background MiT family translocation renal cell carcinoma (TRCC) is a rare and aggressive subgroup of renal cell carcinoma harboring high expression of c-MET. While TRCC response rates to VEGF receptor tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors are limited, efficacy of cabozantinib (a VEGFR, MET, and AXL inhibitor) in this su...

Background COVID-19 disproportionately impacted patients with cancer as a result of direct infection, and delays in diagnosis and therapy. Oncological clinical trials are resource-intensive endeavors that could be particularly susceptible to disruption by the pandemic, but few studies have evaluated the impact of the pandemic on clinical trial cond...

e18766 Background: Patients (pts) with thoracic cancers have a high rate of hospitalization and death from COVID-19. Smoking has been associated with increased risk for severe COVID-19. However, there is limited data evaluating the impact of smoking recency on COVID-19 severity in pts with cancer. We aimed to characterize the clinical outcomes of C...

e16521 Background: Natural killer (NK) cells are thought to play a key role in the immune response against cancer, including clear cell renal cell carcinoma (ccRCC). However, the transcriptomic landscape of NK cells in ccRCC and the mechanisms of NK cell evasion by ccRCC are poorly understood. Methods: We analyzed scRNA-sequencing (10x Genomics) da...

6520 Background: Real-world progression-free survival (rwPFS) and time to next line of therapy (TTNT) are two endpoints of clinical interest in patients with metastatic breast cancer (MBC). Their validation as intermediate endpoints for overall survival (OS), in a real-world setting, remains not fully established. Methods: We conducted a retrospect...

e16522 Background: Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a rare and aggressive tumor with limited clinical trials dedicated to therapeutics for this disease. This retrospective study aimed to report a multi-center experience in the systemic treatment of FH-deficient RCC. Methods: The medical records of patients undergoing...

4549 Background: ChRCC represents about 5% of all kidney cancer and has a dismal prognosis in the metastatic setting, with limited response to immune checkpoint inhibitors (ICI) and targeted therapy. We evaluated the molecular properties of ChRCC and related oncocytic neoplasms to define the tumor immune microenvironment and identify potential ther...

6031 Background: Patients with cancer have worse outcomes from COVID-19 infection. However, the specific impact of COVID-19 on patients with head and neck cancer (HNC) is largely unknown. The COVID-19 and Cancer Consortium (CCC19) maintains an international registry (NCT04354701) aimed to investigate the clinical course and complications of COVID-1...

Immune checkpoint inhibitors (ICIs) have yielded remarkable responses in patients across multiple cancer types, but often lead to immune related adverse events (irAEs). Although a germline cause for irAEs has been hypothesized, no systematic genome wide association study (GWAS) has been performed and no individual variants associated with the overa...

Background Renin-angiotensin system inhibitors (RASi) have been shown to improve outcomes in studies of multiple malignancies by effects on the tumor microenvironment to enhance the immune repertoire and improve drug delivery. Repurposing RASi to treat metastatic renal cell carcinoma (mRCC) in combination with immune-checkpoint inhibitors (ICI) may...

Importance: Non-Hispanic Black individuals experience a higher burden of COVID-19 than the general population; hence, there is an urgent need to characterize the unique clinical course and outcomes of COVID-19 in Black patients with cancer. Objective: To investigate racial disparities in severity of COVID-19 presentation, clinical complications,...

Background: The treatment responses of immune checkpoint inhibitors in metastatic renal cell carcinoma (mRCC) vary, requiring reliable prognostic biomarkers. We assessed the prognostic ability of computed tomography (CT) texture analysis in patients with mRCC treated with programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibit...

Patients with B-lymphoid malignancies have been consistently identified as a population at high risk of severe COVID-19. Whether this is exclusively due to cancer-related deficits in humoral and cellular immunity, or whether risk of severe COVID-19 is increased by anticancer therapy, is uncertain. Using data derived from the COVID-19 and Cancer Con...

343 Background: IO combinations are standard of care for first-line therapy of clear-cell RCC; however, non-clear cell histologies including tRCC were not included in the registrational trials. We previously reported a modest efficacy (objective response rate [ORR] <20%) with IO monotherapy (PD-1 blockade) in tRCC (Boilève et al, JITC. 2018). The e...

281 Background: The COVID-19 pandemic has been associated with a significant disruption in healthcare services including cancer screening and diagnosis. Delays in cancer screening and treatment may lead to increased mortality. We aimed to analyze changes in screening, diagnosis and surgical treatment of common GU malignancies in relation to the COV...

Background The frequency of coinfections and their association with outcomes have not been adequately studied among patients with cancer and COVID-19, a high-risk group for coinfection. Methods We included adult (≥18 years) patients with active or prior hematologic or invasive solid malignancies and laboratory-confirmed SARS-CoV-2 infection, using...

Background Older age is associated with poorer outcomes of SARS-CoV-2 infection, although the heterogeneity of ageing results in some older adults being at greater risk than others. The objective of this study was to quantify the association of a novel geriatric risk index, comprising age, modified Charlson comorbidity index, and Eastern Cooperativ...

Importance The COVID-19 pandemic has had a distinct spatiotemporal pattern in the United States. Patients with cancer are at higher risk of severe complications from COVID-19, but it is not well known whether COVID-19 outcomes in this patient population were associated with geography. Objective To quantify spatiotemporal variation in COVID-19 outc...

The second Kidney Cancer Research Summit was held virtually in October 2020. The meeting gathered worldwide experts in the field of kidney cancer, including basic, translational, and clinical scientists as well as patient advocates. Novel studies were presented, addressing areas of unmet need related to different topics. These include novel metabol...

To accelerate cancer research that correlates biomarkers with clinical endpoints, methods are needed to ascertain outcomes from electronic health records at scale. Here, we train deep natural language processing (NLP) models to extract outcomes for participants with any of 7 solid tumors in a precision oncology study. Outcomes are extracted from 30...

Background Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of anti-neoplastic systemic therapies can result in less robust antibody titres following vaccination and possible risk of breakthrough infection. As clinical...

Importance Androgen deprivation therapy (ADT) has been theorized to decrease the severity of SARS-CoV-2 infection in patients with prostate cancer owing to a potential decrease in the tissue-based expression of the SARS-CoV-2 coreceptor transmembrane protease, serine 2 (TMPRSS2). Objective To examine whether ADT is associated with a decreased rate...

Importance COVID-19 is a life-threatening illness for many patients. Prior studies have established hematologic cancers as a risk factor associated with particularly poor outcomes from COVID-19. To our knowledge, no studies have established a beneficial role for anti–COVID-19 interventions in this at-risk population. Convalescent plasma therapy may...

Introduction Novel non-steroidal anti-androgens (NSAA) are increasingly part of the management of prostate cancer. We aimed to quantify and compare the neurologic side effects of NSAA agents. Materials and methods Phase III randomized controlled trials evaluating NSAAs in the treatment of prostate cancer were selected by two reviewers independentl...

Background: Hospitalized patients with COVID-19 have increased risks of venous (VTE) and arterial thromboembolism (ATE). Active cancer diagnosis and treatment are well-known risk factors; however, a risk assessment model (RAM) for VTE in patients with both cancer and COVID-19 is lacking. Methods: Among patients with cancer in the CCC19 cohort st...

Introduction Patients with lung cancer (LC) are susceptible to severe outcomes from COVID-19. This study evaluated disruption to care of patients with LC during the COVID-19 pandemic. Methods The COVID-19 and Cancer Outcomes Study (CCOS) is a prospective cohort study comprised of patients with a current or past history of hematological or solid ma...

4552 Background: Retrospective studies have shown an association between Ab exposure and inferior clinical outcomes in patients receiving ICI across various tumor types, including mRCC. However, it is unclear whether Ab exposure has a unique interaction with ICI or is an independent prognostic marker, regardless of treatment. We sought to examine A...

4583 Background: The use of High-Dose Corticosteroids (HDC) has been linked to poor outcomes in patients with lung cancer treated with immune checkpoint inhibitors (ICIs) (Ricciuti B, JCO, 2019). There is no data on the effect of HDC on renal cell carcinoma patients (RCC) treated with immunotherapy. We hypothesized that HDC use would be associated...

6563 Background: Immunodeficiency in patients (pts) with cancer can lead to the progression of common respiratory viral infections to lower respiratory tract disease (LRTD) with potentially high mortality. Understanding risk factors of SARS-CoV-2 related LRTD in pts with cancer is imperative for the development of preventive measures. Methods: We e...

4529 Background: Oncology patients experience more severe disease outcomes from COVID-19 infection than the general population. BCG is a live bovine tuberculosis bacillus with immunotherapeutic effects in urothelial cancers; it is also used as vaccination against Mycobacterium tuberculosis in parts of the world. As BCG vaccination has been associat...