Making the rounds: Exploring the role of circulating tumor DNA (ctDNA) in non-small cell lung cancer

Advancements in the clinical practice of non-small cell lung cancer (NSCLC) are shifting treatment paradigms towards increasingly personalized approaches. Liquid biopsies using various circulating analytes provide minimally invasive methods of sampling the molecular content within tumor cells. Plasma-derived circulating tumor DNA (ctDNA), the tumor-derived component of cell-free DNA (cfDNA), is the most extensively studied analyte and has a growing list of applications in the clinical management of NSCLC. As an alternative to tumor genotyping, the assessment of oncogenic driver alterations by ctDNA has become an accepted companion diagnostic via both single-gene polymerase chain reactions (PCR) and next-generation sequencing (NGS) for advanced NSCLC. ctDNA technologies have also shown the ability to detect the emerging mechanisms of acquired resistance that evolve after targeted therapy. Furthermore, the detection of minimal residual disease (MRD) by ctDNA for patients with NSCLC after curative-intent treatment may serve as a prognostic and potentially predictive biomarker for recurrence and response to therapy, respectively. Finally, ctDNA analysis via mutational, methylation, and/or fragmentation multi-omic profiling offers the potential for improving early lung cancer detection. In this review, we discuss the role of ctDNA in each of these capacities, namely, for molecular profiling, treatment response monitoring, MRD detection, and early cancer detection of NSCLC

Therapeutic Vaccines for Genitourinary Malignancies

The field of genitourinary malignancies has been a showcase for therapeutic cancer vaccine success since the application of intravesicular Bacillus Calmette-Guerin (BCG) for bladder cancer in the 1970s and enjoyed a renaissance in 2010 with the US Food and Drug Administration (FDA) approval of sipuleucel-T for prostate cancer. Several vaccine strategies have emerged, such as autologous or allogeneic whole-tumor vaccines, DNA vaccines, use of viral vectors, and peptides as immunostimulatory adjuvants. Despite impressive early trials, vaccine monotherapy has achieved limited success in the clinical world; however, combinations of vaccine and immune checkpoint inhibition or vaccine and cytokine stimulation are expected to move the field forward. This article reviews pivotal trials of cancer vaccines in prostate, renal, and bladder cancer and ongoing trials combining vaccines with other immune therapy agents

Unusual Presentation of Renal Medullary Carcinoma With Undiagnosed Sickle Cell Trait

Renal medullary carcinoma (RMC) is an extremely rare malignancy that has been described in younger male patients of African descent with a history of sickle cell disease or trait. We describe a rather unique case of RMC in an older male patient who initially presented with acute on chronic urinary retention and concern for infection. Further investigation revealed a history of hematuria and long-standing microcytic anemia, and the patient was found to have sickle cell trait (SCT) as part of a workup for malignancy of unknown primary. Imaging findings initially interpreted as hydronephrosis later characterized a mass in the renal pelvis concerning for a genitourinary malignancy, later biopsy-proven RMC. RMC typically presents in its advanced stages, with associated poor prognosis, and treatment options are limited and have been extrapolated from standard regimens for other genitourinary malignancies. Therefore, early clinical suspicion in patients with microcytic anemia, flank pain, hematuria, and urinary symptoms, can aid in the diagnosis of RMC and allow for prompt intervention

Making the Rounds: Exploring the Role of Circulating Tumor DNA (ctDNA) in Non-Small Cell Lung Cancer

Advancements in the clinical practice of non-small cell lung cancer (NSCLC) are shifting treatment paradigms towards increasingly personalized approaches. Liquid biopsies using various circulating analytes provide minimally invasive methods of sampling the molecular content within tumor cells. Plasma-derived circulating tumor DNA (ctDNA), the tumor-derived component of cell-free DNA (cfDNA), is the most extensively studied analyte and has a growing list of applications in the clinical management of NSCLC. As an alternative to tumor genotyping, the assessment of oncogenic driver alterations by ctDNA has become an accepted companion diagnostic via both single-gene polymerase chain reactions (PCR) and next-generation sequencing (NGS) for advanced NSCLC. ctDNA technologies have also shown the ability to detect the emerging mechanisms of acquired resistance that evolve after targeted therapy. Furthermore, the detection of minimal residual disease (MRD) by ctDNA for patients with NSCLC after curative-intent treatment may serve as a prognostic and potentially predictive biomarker for recurrence and response to therapy, respectively. Finally, ctDNA analysis via mutational, methylation, and/or fragmentation multi-omic profiling offers the potential for improving early lung cancer detection. In this review, we discuss the role of ctDNA in each of these capacities, namely, for molecular profiling, treatment response monitoring, MRD detection, and early cancer detection of NSCLC

Genomic profiling by cell-free circulating tumor DNA in patients with recurrent adenoid cystic carcinoma (ACC) and the potential activity of selective fibroblast growth factor receptor (FGFR) inhibitors

e15018 Background: Few effective systemic therapies are available for adenoid cystic carcinoma (ACC). Multitargeted Tyrosine Kinase inhibitors (TKIs) as Lenvatinib and Rivoceranib can provide disease control and limited radiographic response in unselected ACC patients. Next-generation sequencing in tissue (tNGS) has identified MYB gene fusions in [patients with ACC but currently, only Notch1 mutations have an available targeted agent. The fibroblast growth factor receptor (FGFR) pathway is a downstream target of MYB. Methods: We retrospectively reviewed adult patients with a diagnosis of recurrent ACC seen at the University of Miami Sylvester Comprehensive Cancer Center between January 1, 2019 and October 31, 2020. Commercially available cell free DNA panel of 73 genes was used for analyzing circulating tumor DNA (ctDNA). Patients included had radiographically measurable disease and both tNGS and ctDNA data available. Results: Twelve patients were included. Median age at diagnosis was 54 years (28 - 68), and 69% were males. 83% of the patients had genomic abnormalities reported by tNGS, with the same number by ctDNA sequencing. Seven patients (58%) had genomic abnormalities in ctDNA of potentially therapeutic significance which were not found on tNGS, including FGFR1 amplification as well as FGFR2, BRAF, KRAS and JAK2 mutations. Three patients with FGFR genomic abnormalities only seen by ctDNA had been previously treated with Lenvatinib. One patient with primary lacrimal gland ACC metastatic to the liver and tNGS positive for NOTCH 1 had disease progression despite treatment with Lenvatinib and a NOTCH γ-secretase inhibitor. The patient’s ctDNA reported a FGFR2 mutation. The patient was started on Erdafitinib, an oral selective FGFR inhibitor, achieving a partial response at the primary site and metastatic liver lesions and remained on therapy for 7 months. Follow-up ctDNA after 3 months of therapy noted resolution of both FGFR and NOTCH abnormalities. Conclusions: Patients treated with lenvantinib or other TKIs may develop acquired resistance mutations and other genomic abnormalities. ctDNA can reveal additional therapeutic targets not present on tNGS and can be repeated serially. FGFR genomic abnormalities can be a driver mutation in patients with refractory advanced ACC and the activity of Erdafinib should be evaluated in this subset of patients with few therapeutic options

Abstract B123: Prevalence of COVID-19 among hematology/oncology patients and providers of a community-facing county health system during the B1.1.529 (“Omicron”) SARS-CoV-2 variant wave

Abstract Introduction: The SARS-CoV-2 (COVID-19) pandemic continues in the United States, and patients actively receiving chemotherapy are known to be at enhanced risk for developing symptomatic disease. Our study evaluated the prevalence of COVID-19 among patients and providers of our community-facing county health system during the B1.1.529 (“Omicron”) COVID-19 variant wave. Methods: We retrospectively analyzed patients that received care and clinical providers whom worked at the Jackson Memorial Hospital Hematology/Oncology clinic in Miami, Florida from December 1st, 2021 through April 30th, 2022. After categorizing basic demographic factors for individuals whom tested positive for COVID-19 during the study timeframe, we analyzed additional risk factors leading to COVID-19 positivity including, but not limited to, vaccination status, previous COVID-19 positivity, and active receipt of chemotherapeutics. We then analyzed outcomes related to COVID-19, including treatment with advanced COVID-19 therapies such as oral or intravenous antivirals, monoclonal antibodies, convalescent plasma, steroids, or interleukin-6 inhibitors; interactions with inpatient services including emergency department (ED)/urgent care visits, inpatient and/or ICU admissions, and deaths from COVID-19. We finally assessed quality outcomes such as delay in cancer-directed therapy. This study was approved by the University of Miami IRB and Jackson Health System Clinical Trials Office. Results: 498 patients and 18 providers were retrospectively analyzed during the study timeframe. 49 patients tested positive for COVID-19 (9.84%), while 6 providers tested positive (33.3%) (p = 0.015). Patients whom tested positive were 51.0% female (n = 25), 26.5% Black (n = 13), 73.5% Hispanic/Latinx (n = 36), and 2.05% Asian (n = 1). Only 6.12% patients had tested positive for COVID-19 previously (n = 3), and 42.9% were considered unvaccinated (n = 21) while 14.3% were boosted (n = 7). 73.5% (n = 36) presented with symptomatic disease, 46.9% (n = 23) sought care at an ED/urgent care, 32.6% (n = 13) were admitted to the hospital, 6.12% were admitted to the ICU (n = 3), and 16.3% (n = 8) received advanced therapeutics. There were 2 (8.0%) COVID-19-related deaths (and another outside our study timeframe) among 23 non-COVID-19 related deaths in the patient population (p = 0.75). More than half of the patients whom tested positive experienced a cancer treatment delay (n = 27/49; 55.1%). Conclusions: The prevalence of COVID-19 positivity in our patient cohort during the initial Omicron wave mirrored local, state, and national trends, however a statistically significant greater proportion of our providers tested positive. COVID-19 positivity conferred appreciable disparities in the presentation of disease as well as receipt of cancer treatment. COVID-19 positivity was more likely to result in symptomatic disease and ED/urgent care visit in cancer patients without previous COVID infection and unvaccinated status. COVID-19 accounted for 8.0% of our clinic’s total mortality. Citation Format: Aliya Khan, Samuel A. Kareff, Priscila Barreto-Coelho, Sunil Iyer, Brian Pico, Michele Stanchina, Giselle Dutcher, José Monteiro de Oliveira Novaes, Aparna Nallagangula, Gilberto Lopes. Prevalence of COVID-19 among hematology/oncology patients and providers of a community-facing county health system during the B1.1.529 (“Omicron”) SARS-CoV-2 variant wave [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B123