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.

Subjective and Objective Hearing Loss Among US Adult Cancer Survivors.

Importance: Cancer survivors are at a higher risk of developing hearing loss (HL) due to older age, chemotherapy, and radiotherapy. However, the prevalence of HL among US cancer survivors remains unknown. Additionally, there is a lack of uniform HL screening guidelines for this enlarging population. Objective: To estimate the prevalence of subjective HL and objective HL by audiometry test among cancer survivors and compare them with the general population as well as to assess the performance of subjective HL questions in detecting true (ie, audiometry-confirmed) HL. Design, Setting, and Participants: In a cross-sectional design, adults between ages 20 and 80 years who had audiometry testing and responded to a hearing questionnaire from the National Health and Nutrition Examination Survey (2011-2012, 2015-2016, and 2017 to March 2020 prepandemic survey cycles) were selected. Data analysis was conducted from August 13, 2022, to July 26, 2023. Main Outcomes and Measures: The weighted prevalence of subjective HL (troublesome hearing and tinnitus) and objective HL (speech-frequency HL and high-frequency HL) by audiometry were calculated. Analyses with χ2 testing and multiadjusted logistic regression models were used to compare HL between cancer survivors and the general population. To evaluate the performance of subjective HL questions as a tool to screen for objective HL by audiometry, areas under the curve were estimated using age- and gender-adjusted logistic regression. Results: Among the total 9337 participants (weighted n = 90 098 441; 51.2% women), 10.3% were cancer survivors. Compared with the general population, cancer survivors had a higher prevalence of troublesome hearing (adjusted odds ratio [AOR], 1.43; 95% CI, 1.11-1.84), tinnitus (AOR, 1.28; 95% CI, 0.94-1.74), speech-frequency HL (AOR, 1.43; 95% CI, 1.11-1.85), and high-frequency HL (AOR, 1.74; 95% CI, 1.29-2.34). When using the subjective HL tool and questioning regarding whether the participants were having troublesome hearing and/or tinnitus in screening for HL, the age- and gender-adjusted area under the curve was 0.88 in detecting speech-frequency HL and 0.90 in detecting high-frequency HL. Conclusion and Relevance: The findings of this study suggest that cancer survivors have a significantly higher prevalence of HL than the general population. Two subjective HL questions could potentially accurately identify those who have true HL and provide a simple and efficient screening tool for health care professionals. Cancer survivors and their families should be educated and encouraged to discuss hearing concerns, and health care professionals should facilitate raising awareness and provide early screening and timely referral when HL is identified.

Prevalence and Outcomes of COVID-19 among Hematology/Oncology Patients and Providers of a Community-Facing Health System during the B1.1.529 ("Omicron") SARS-CoV-2 Variant Wave.

(1) Background: the SARS-CoV-2 (COVID-19) pandemic continues, and patients actively receiving chemotherapy are known to be at enhanced risk for developing symptomatic disease with poorer outcomes. 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. (2) Methods: We retrospectively analyzed patients that received care and clinical providers whom worked at the Jackson Memorial Hospital Hematology/Oncology clinic in Miami, Florida, USA, from 1 December 2021 through 30 April 2022. We assessed demographic variables and quality outcomes among patients. (3) Results: 1031 patients and 18 providers were retrospectively analyzed. 90 patients tested positive for COVID-19 (8.73%), while 6 providers tested positive (33.3%) (p = 0.038). There were 4 (10.3%) COVID-19-related deaths (and another outside our study timeframe) and 39 non-COVID-19-related deaths (89.7%) in the patient population (p = 0.77). COVID-19 accounted for 4.44% of our clinic's total mortality, and delayed care in 64.4% of patients. (4) Conclusions: The prevalence of COVID-19 positivity in our patient cohort mirrored local, state, and national trends, however a statistically significant greater proportion of our providers tested positive. Almost two-thirds of patients experienced a cancer treatment delay, significantly impacting oncologic care.

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.

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.

Association Between Pretreatment Neutrophil-to-Lymphocyte Ratio and Outcome of Patients With Metastatic Renal-Cell Carcinoma Treated With Nivolumab.

BACKGROUND: Biomarkers to guide treatment in metastatic renal-cell carcinoma (mRCC) are lacking. We aimed to investigate the association between pretreatment neutrophil-to-lymphocyte ratio (NLR) and outcome of patients with mRCC receiving nivolumab. PATIENTS AND METHODS: Through retrospective chart review, we identified 38 patients with mRCC treated with standard-of-care nivolumab between 2015 and 2016 at Winship Cancer Institute of Emory University. NLR was determined from complete blood count collected before starting treatment, and imaging was performed to assess progression. The NLR cutoff value of 5.5 was determined by log-rank test, and the univariate association with overall survival (OS) or progression-free survival (PFS) was assessed by the Cox proportional hazard model and Kaplan-Meier method. RESULTS: The 38 patients had a median age of 69 years. The PFS and OS for all patients at 12 months was 54% and 69%, respectively. The median PFS was 2.6 months in the high NLR group but not reached in the low NLR group. Low NLR was strongly associated with increased PFS with hazard ratio of 0.20 (95% confidence interval, 0.07-0.64; P = .006). The median OS was 2.7 months in the high NLR group but not reached in the low NLR group. Low NLR was significantly associated with a prolonged OS with hazard ratio of 0.06 (95% confidence interval, 0.01-0.55; P = .012). CONCLUSION: Pretreatment NLR < 5.5 is associated with superior PFS and OS. NLR is a biomarker that can inform prognosis for patients with mRCC and should be further validated in larger cohorts and in prospective studies.