National Cancer Institute Centers With Environmental Sustainability Plans for Climate Change.

This qualitative study investigates environmental sustainability plans at National Cancer Institute Comprehensive Cancer Centers and affiliated institutions.

Novel biomarkers in NSCLC: Radiomic analysis, kinetic analysis, and circulating tumor DNA.

Current radiographic methods of measuring treatment response for patients with nonsmall cell lung cancer have significant limitations. Recently, new modalities using standard of care images or minimally invasive blood-based DNA tests have gained interest as methods of evaluating treatment response. This article highlights three emerging modalities: radiomic analysis, kinetic analysis and serum-based measurement of circulating tumor DNA, with a focus on the clinical evidence supporting these methods. Additionally, we discuss the possibility of combining these modalities to develop a robust biomarker with strong correlation to clinically meaningful outcomes that could impact clinical trial design and patient care. At Last, we focus on how these methods specifically apply to a Veteran population.

New targeted and epigenetic therapeutic strategies for the treatment of uveal melanoma.

Uveal melanoma (UM) is a rare, genetically bland ocular malignancy with excellent local treatment options, but no disease-specific therapies are approved for use in the metastatic setting by the Food and Drug Administration. Metastatic UM (mUM) confers a prognosis of ~15 months. Unlike cutaneous melanoma, UM is poorly responsive to checkpoint inhibitors and cytotoxic chemotherapy highlighting the importance of clarifying vulnerable disease-specific mechanisms, such as cell cycle or metabolic pathways necessary for tumor growth and survival. The elucidation of signaling pathways downstream of the frequently mutated GNA GTPase such as PKC/MAPK/ERK/MEK, PI3K/AKT, and YAP-Hippo have offered potential targets. Potentially druggable epigenetic targets due to BAP1-mutated UM have also been identified, including proteins involved with histone deacetylation and DNA splicing. This review describes the preclinical rationale for the development of targeted therapies and current strategies currently being studied in clinical trials or will be in the near future.

Evaluating management of progressive disease for control arm patients in trials of first line PD-1 or PD-L1 inhibitor-based treatment for metastatic solid tumours.

INTRODUCTION: First-line trials evaluating programmed cell death protein 1/programmed-death ligand 1 inhibitors (PDI) are often preceded by FDA approvals of PDI in second-line settings; however, many control-arm patients in these first-line trials do not receive PDI at disease progression. We performed a systematic analysis of trials evaluating upfront use of PDI in metastatic solid tumours to (1) quantify the number of control-arm patients that receive PDI upon disease progression and (2) the timing difference between FDA approval for a PDI in the second-line setting and (3) enrolment period for the same drug in a first-line trial. METHODS: Using the Drugs@FDA website, we evaluated all approvals for first-line and second-line PDI in metastatic solid tumours through December 2021. From corresponding trials, we calculated the timing difference between second-line approval of a PDI and start/end of accrual of first-line trials and management of disease progression for control-arm patients. RESULTS: 25/32 approvals for upfront PDI were preceded by approval of a PDI in the second-line of the same disease and included in this analysis. First-line trials start of accrual preceded approval of a PDI by a mean of 4 months, median 6 months and ended accrual by a mean and median of 14 after second-line approval. A mean of 51% of control-arm patients received subsequent therapy, with a mean of 33% of these patients receiving a PDI. CONCLUSION: This analysis shows that many control-arm patients in the included trials did not receive a PDI with already established efficacy at any point during their recorded treatment. This underscores a need to standardise the approach to disease progression for control-arm patients to reflect evolving standards of care. This analysis is limited by a lack of individual patient-level data, heterogeneity of included trials and exclusion of first-line PDI trials that did not meet their primary endpoint.

Tebentafusp in advanced uveal melanoma: proof of principle for the efficacy of T-cell receptor therapeutics and bispecifics in solid tumors.

INTRODUCTION: Tebentafusp is a novel bispecific immune mobilizing T cell receptor (TCR)-based agent developed for the treatment of metastatic uveal melanoma, a highly fatal disease with no currently approved treatment options. Recent evidence suggests this drug may become the standard of care for first-line treatment of metastatic uveal melanoma. AREAS COVERED: This review focuses on the development and investigation of tebentafusp for metastatic uveal melanoma. First, we discuss preclinical studies followed by clinical evaluation, culminating in a phase III trial showing improved overall survival with tebentafusp compared to standard of care. Finally, we expand upon key toxicities of tebentafusp and highlight biomarkers that may correlate with drug efficacy. EXPERT OPINION: Tebentafusp provides a promising advancement to date for the management of metastatic uveal melanoma. Future studies should aim at identifying biomarkers that can predict treatment response or toxicity, combination therapy, application of tebentafusp in the adjuvant setting to reduce the risk of recurrence, and development of bispecifics with activity in other HLA subtypes. With its novel mechanism of action, degree of efficacy and safety profile, tebentafusp is expected to change the standard of care for treating metastatic and, potentially localized, uveal melanoma.

Patterns of palliative care consultation among patients with brain metastasis: an opportunity for radiation oncologists to facilitate earlier referral.

BACKGROUND: Early palliative care (PC) physician involvement alongside standard oncologic care has been recommended by the American Society of Clinical Oncology (ASCO) guidelines for all advanced cancer patients, although adherence to these guidelines is variable. Radiation oncologists (ROs) could help facilitate early PC referral for patients treated with palliative radiation, particularly those with brain metastasis (BRM), and the aim of this study was to evaluate the circumstances of PC referral at our institution to better understand the multidisciplinary approaches to facilitate it. METHODS: Patients diagnosed with BRM from non-small cell lung cancer (NSCLC) from 2012 to 2018 whose primary RO and MO were at our institution were reviewed. Overall survival and time to PC consultation from the first oncologic visit following BRM diagnosis was determined using the KaplanMeier method. Mann-Whitney U and Chi-Squared assessed for predictive factors for shorter time to PC consultation. For these factors, the overall survival, rate of PC consultation, and PC setting was used to determine utilization of early PC. RESULTS: Among 103 eligible patients, only 48% underwent a PC consultation in their lifetime, with the initial evaluation being as an outpatient for 37%, and within 1 month of death for 35%. Median survival from BRM diagnosis was 9.0 months. The median time from oncologic appointment to PC referral was 2.8 months, and from initial PC consultation to death was 1.6 months. Only more recent BRM diagnosis (2016-2018 vs. 2012-2015) was associated with shorter time to PC consultation (1.0 vs. 5.6 months, P=0.013), increased PC consult rate (60% vs. 42%, P=0.105), and increased outpatient PC consultation (56% vs. 26%, P=0.037). CONCLUSIONS: The majority of patients did not undergo early PC consultation, though utilization has improved over time. As ROs are commonly involved in BRM management, they may be in a position to proactively support early PC consultations in this patient population.

The Relationship Between Checkpoint Inhibitors and the Gut Microbiome and Its Application in Prostate Cancer.

Indications for checkpoint inhibitors (CPIs) are growing rapidly within the field of oncology; however, they continue to have heterogeneous outcomes in different cancers. Other than mismatch repair deficiency, there are no consistent tests to determine a tumor's susceptibility. By exploring factors beyond the cancer cell, researchers have learned that the efficacy of CPIs may be governed by a myriad of variable host factors, including the tumor microenvironment (TME) and gut microbiome (GMB). The GMB serves as one of the primary organs of immune defense and has well-established local and systemic effects on the host immune system. Recent investigations suggest that the GMB also affects the TME. This review article discusses the concepts of a TME and a GMB and their effects on responses to CPIs. It also reviews recent research investigating these 3 topics, and how it can be applied to using CPIs in prostate cancer. By highlighting this important pathophysiologic process, we hope to provide insight into a possible explanation for differences in interindividual response to CPIs, discuss a potential method for transferring treatment efficacy between patients, and propose a method for expanding the use of CPIs to prostate cancer.

The efficacy and safety of a catheter removal only strategy for the treatment of PICC line thrombosis versus standard of care anticoagulation: a retrospective review.

Peripherally-inserted central catheters (PICCs) are commonly used during hospitalization. Unfortunately, their use can be complicated by catheter-related thrombosis (CRT). Current guidelines recommend 3-6 months of anticoagulation for patients with CRT after catheter removal. This recommendation is based on extrapolation of data on lower extremity thrombosis, as data is lacking regarding the efficacy and safety of more specific management strategies. Many providers feel catheter removal alone is a reasonable treatment option, particularly for patients at risk for bleeding. We performed a retrospective analysis of hospitalized adult patients diagnosed with CRT at our center. We determined rates of progressive thrombosis and bleeding in cohorts of patients who underwent catheter removal vs those who had catheters removed and received anticoagulation. Among 83 total patients, 62 were treated with PICC removal alone, while 21 underwent PICC removal followed by therapeutic anticoagulation. Patients treated with PICC removal alone were more likely to have hematologic malignancy, receive chemotherapy, develop thrombocytopenia, and have brachial vein thrombosis. No patients in the PICC removal plus anticoagulation arm developed progressive thrombosis, while 6.4% of patients treated with catheter removal alone developed a secondary VTE event, including one PE, three DVTs, and five patients (8%) who developed progressive symptoms leading to initiation of anticoagulation. Major bleeding was significantly more common in the PICC removal + anticoagulation arm (28.5% vs. 4.8% p = 0.007). Catheter-removal alone results in significantly reduced major bleeding compared with catheter-removal plus anticoagulation. In select patients, catheter removal alone may be an option for CRT.