Solid Malignancies Research Articles

DNA demethylation triggers cell free DNA release in colorectal cancer cells

BackgroundLiquid biopsy based on cell-free DNA (cfDNA) analysis holds significant promise as a minimally invasive approach for the diagnosis, genotyping, and monitoring of solid malignancies. Human tumors release cfDNA in the bloodstream through a combination of events, including cell death, active and passive release. However, the precise mechanisms leading to cfDNA shedding remain to be characterized. Addressing this question in patients is confounded by several factors, such as tumor burden extent, anatomical and vasculature barriers, and release of nucleic acids from normal cells. In this work, we exploited cancer models to dissect basic mechanisms of DNA release.MethodsWe measured cell loss ratio, doubling time, and cfDNA release in the supernatant of a colorectal cancer (CRC) cell line collection (N = 76) representative of the molecular subtypes previously identified in cancer patients. Association analyses between quantitative parameters of cfDNA release, cell proliferation, and molecular features were evaluated. Functional experiments were performed to test the impact of modulating DNA methylation on cfDNA release.ResultsHigher levels of supernatant cfDNA were significantly associated with slower cell cycling and increased cell death. In addition, a higher cfDNA shedding was found in non-CpG Island Methylator Phenotype (CIMP) models. These results indicate a positive correlation between lower methylation and increased cfDNA levels. To explore this further, we exploited methylation microarrays to identify a subset of probes significantly associated with cfDNA shedding and derive a methylation signature capable of discriminating high from low cfDNA releasers. We applied this signature to an independent set of 176 CRC cell lines and patient derived organoids to select 14 models predicted to be low or high releasers. The methylation profile successfully predicted the amount of cfDNA released in the supernatant. At the functional level, genetic ablation of DNA methyl-transferases increased chromatin accessibility and DNA fragmentation, leading to increased cfDNA release in isogenic CRC cell lines. Furthermore, in vitro treatment of five low releaser CRC cells with a demethylating agent was able to induce a significant increase in cfDNA shedding.ConclusionsMethylation status of cancer cell lines contributes to the variability of cfDNA shedding in vitro. Changes in methylation pattern are associated with cfDNA release levels and might be exploited to increase sensitivity of liquid biopsy assays.

A first-in-human phase 1 study of BXQ-350, a first-in-class sphingolipid metabolism regulator, in patients with advanced/recurrent solid tumors or high-grade gliomas.

BXQ-350, a nanovesicle formulation of Saposin C, is an allosteric sphingolipid metabolism regulator that increases pro-apoptotic ceramide and decreases oncogenic sphingosine-1-phosphate (S1P) levels. We conducted a first-in-human, phase 1 study of BXQ-350. Adults (≥18 years old) with advanced/recurrent, treatment-refractory solid tumors or high-grade gliomas received BXQ-350 intravenously in five dose cohorts (0.7-2.4 mg/kg) in a 3+3 dose-escalation and expansion design. Primary endpoints during dose escalation were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD); primary objective in expansion parts was assessment of anti-tumor activity (RECIST v1.1/RANO criteria). Eighty-six patients were enrolled. DLTs were not observed during dose escalation (n=18), and a MTD was not identified. An additional 68 patients received the 2.4 mg/kg dose. Nine patients (10%) discontinued due to adverse events (AEs). The most common treatment-related AEs were nausea (24%) and fatigue (23%). Eight patients had a progression-free survival (PFS) ≥6 months. Two of these achieved a partial response, and six had stable disease, among whom three had a reduction in ≥1 target lesion. Of those with PFS ≥6 months, seven remained on study for >12 months, five for >24 months, and after seven years, two remained on study without disease progression. BXQ-350 was well tolerated as monotherapy at doses up to 2.4 mg/kg. It provided some lasting clinical benefit in patients with recurrent solid malignancies across several tumor types, consistent with a decreased systemic S1P/ceramide metabolic rheostat. BXQ-350 warrants further clinical investigation alone and combined with standard-of-care for advanced solid tumors.

8270 A Rare Case Of PTHrP Induced Severe Hypercalcemia Secondary To Squamous Cell Carcinoma Of Tongue

Abstract Disclosure: N. Vennelaganti: None. S. Vennelaganti: None. K. McCowen: None. Background: PTHrP-mediated hypercalcemia is often associated with solid organ malignancies and indicates a poor prognosis. The occurrence of this condition due to SCC of the head and neck, particularly of the tongue, is uncommon. This case report aims to shed light on this rare clinical presentation. Clinical Case: A 70-year-old woman with a history of tobacco use disorder, alcoholic liver cirrhosis, and a chronic fungal prosthetic joint infection presented with altered mental status and acute kidney injury. Laboratory tests revealed a corrected calcium level of 15.4 mg/dL and suppressed PTH of 3 pg/mL, indicating non-PTH-dependent hypercalcemia. Differentials considered included malignancy, multiple myeloma, 1,25 OH Vit D mediated hypercalcemia via fungal granuloma formation, and immobilization. Diagnostic evaluation revealed normal levels of 25 hydroxy Vitamin D ie: 54 ng/mL, normal kappa to lambda ratio suggestive of negative myeloma screen, normal TSH of 2.81 uIU/mL, and a low 1,25 OH Vit D level ie: 11.4 pg/mL (Ref range: 19.9-79.3 pg/mL). An elevated PTHrP concentration of 9.7 pmol/L (ref range 0-3.4 pmol/L) was noted. CT angiography performed for stroke evaluation incidentally discovered a base of tongue mass, which was difficult to appreciate on exam due to obtundation. A biopsy confirmed SCC of the tongue, and she was determined to be Stage IVA. The patient's hypercalcemia was determined to be secondary to PTHrP production from the tongue SCC compounded by immobilization. She was treated with IV fluids and subcutaneous calcitonin, normalizing her calcium levels over 20 days. IV Bisphosphonates were held inpatient due to poor renal function. She was seen by oncology and determined to not be fit for surgical management or chemotherapy. Radiation therapy was advised for management and patient was discharged. While awaiting her outpatient radiation treatment, the patient had another episode of altered mental status and was found to have a serum calcium of 16.4 mg/dL. She was managed with IV fluids, calcitonin and IV Zoledronate which improved her serum calcium. She has since been receiving monthly IV Zometa with oncology for hypercalcemia of malignancy. She was recently readmitted with severe oropharyngeal and pharyngeal dysphagia and has received a PEG tube for feeding. She is still pending radiation therapy for SCC tongue. Conclusion: Initially, during the workup of this case, we believed her hypercalcemia was likely immobilization-induced, but thorough investigation and the elevated PTHrP levels steered us towards malignancy as a potential etiology. This case is an example of an occult malignancy which lead to severe hypercalcemia. It also contributes to the understanding of hypercalcemia in cancer patients and highlights the rare association of SCC of the tongue with PTHrP-mediated hypercalcemia . PTHrP secreting SCC of head and neck are typically associated with a poor prognosis. Presentation: 6/2/2024

Tolerability Assessment of Tyrosine Kinase Inhibitors in Patients With Solid Tumor Malignancies and Hypoalbuminemia.

Hypoalbuminemia is common in patients with advanced solid tumor malignancies. However, despite the increased use of highly protein-bound tyrosine kinase inhibitors (TKIs) in cancer treatments, the tolerability of these agents in patients with hypoalbuminemia is not fully known. Our aim is to assess whether patients on oral TKIs with hypoalbuminemia are at higher risk for experiencing medication-related adverse events, therefore requiring careful considerations. This is a single-center, retrospective study including patients ≥18 years of age with a solid tumor malignancy who had taken at least one dose of oral TKIs with a protein binding of ≥90% between June 1, 2016, and June 1, 2021. The primary outcome was to compare time to TKI discontinuation due to adverse events between patients with and without hypoalbuminemia. Key secondary outcomes include TKI discontinuation and dose reduction rates, time to TKI dose reduction, and severity of adverse events. Out of 282 included patients, 134 (48%) patients had hypoalbuminemia and 148 (52%) had normal albumin levels. Compared with patients without hypoalbuminemia, patients with hypoalbuminemia had shorter median time on treatment at 2.8 months (95% CI = 2.3-4.5 months) versus 4.3 months (95% CI = 2.8-6.4 months; P = 0.003). In patients who had TKI discontinuation, dose reduction was associated with longer time on treatment in patients in the normal albumin group compared with patients in the hypoalbuminemia group or patients without dose reduction (P < 0.0001). Patients in the hypoalbuminemia group experienced significantly more grade 3/4 adverse events compared with those in the normal albumin group (73% vs 27%, P < 0.0001). Hypoalbuminemia is a risk factor for both shorter time on treatment and more severe adverse events in patients with solid tumor malignancies taking highly protein-bound oral TKIs. This study highlights the need for closer monitoring of this patient population by health care providers.

Association of Participation in Medicare's Oncology Care Model With Spending, Utilization, and Quality Outcomes Among Commercially Insured and Medicare Advantage Members.

The Oncology Care Model (OCM), a value-based payment model for traditional Medicare beneficiaries with cancer, yielded total spending reductions that were outweighed by incentive payments, resulting in net losses to the Centers for Medicare & Medicaid Services. We studied whether the OCM yielded spillover effects in total episode spending, utilization, and quality among commercially insured and Medicare Advantage (MA) members, who were not targeted by the program. This observational study used administrative claims from a large national payer, yielding 157,189 total patients with commercial insurance or MA with solid malignancies who initiated 229,376 systemic anticancer therapy episodes before (2012-2015) and during (2016-2021) the OCM at 125 OCM-participating practices (a subset of total OCM practices) and a 1:10 propensity-matched set of 860 non-OCM practices. We used difference-in-differences analyses to assess the association between the OCM and total episode spending, defined as medical spending during a 6-month episode. Secondary outcomes included hospitalization and emergency department (ED) utilization and quality measures. From the pre-OCM to the OCM period, mean total episode payments increased from $45,504 in US dollars (USD) to $46,239 USD for OCM-participating practices, and increased from $50,519 USD to $58,591 USD for non-OCM practices (adjusted difference-in-differences -$6,287 USD [95% CI, -$10,076 USD to -$2,498 USD], P = .001). The OCM was associated with adjusted spending decreases for both high-risk (-$6,756 USD [95% CI, -$10,731 USD to -$2,781 USD], P = .001) and low-risk (-$4,171 USD [95% CI, -$7,799 USD to -$543 USD], P = .025) episodes. OCM-associated spending reductions were strongest for outpatient (-$5,243 USD [95% CI, -$8,589 USD to -$1,897 USD], P = .002) and infused/injected anticancer drug (-$3,031 USD [95% CI, -$5,193 USD to -$869 USD], P = .006) spending. There were no associations between OCM participation and changes in hospital or ED utilization nor quality of care. The OCM was associated with reductions in spending for nontargeted members, a spillover effect.

Impact of household income on survival in solid malignancies with synchronous brain metastases: A population-based study.

142 Background: Solid malignancies presenting with brain metastasis at the initial diagnosis usually carry a poor prognosis. Increased incidence of brain metastasis can be attributed to the advancements in neuroimaging techniques and improvements in the treatment of solid malignancies. The role of socioeconomic factors in cancer survival is being increasingly recognized. In this study, we analyzed the effect of median household income on survival outcomes in patients diagnosed with brain metastasis at the time of diagnosis of primary malignancies from 2010 to 2020. Methods: We analyzed the Surveillance, Epidemiology, and End Results (SEER) Program 17 registry (November 2022 submission) database for four primary sites of cancers based on their high propensity to develop brain metastases- Lung and/or Bronchus, Breast, Kidney and/or Renal Pelvis, and Melanoma. Patients with a median household income (MHHI) greater than 75,000 per year were classified as a high-income group, whereas those less than 75,000 per year were low-income. Patients diagnosed with malignancy during autopsy or via death certificate and with incomplete data were excluded. Kaplan-Meier method was used for 2-year survival rates and overall survival analyses. Cox regression analysis was used to calculate hazard ratios (HR). Results: A total of 66493 patients were identified across the four primary sites of tumors. Lung and/or bronchus tumors comprised most of the cases (n = 58,324). 25337 patients were in the high-income group, and 41156 patients comprised the low-income group. Median survival in the low-income group was 4 months, and in the high-income group was 5 months, with a 2-year survival rate of 11% and 18% respectively. Patients in the high-income group had better survival outcomes than the low-income [HR:0.88, 95% CI:0.86-0.90, p&lt;0.001]. Additionally, the high-income group had 19% higher odds of receiving chemotherapy [OR:1.19, 95% CI:1.16-1.23, p&lt;0.0001]. Amongst the cancer subgroups, household income did not have a significant effect on survival in patients with kidney and/or renal pelvis tumors [HR:0.97, 95% CI:0.88-1.06, p=0.5]. The 2-year survival rates are outlined (Table). Conclusions: Our analysis highlights a modest improvement in survival in the patient population with higher median household income. This difference could be attributed to the greater accessibility to treatment modalities and other resources for patients with higher household incomes. Further studies are needed to address socioeconomic disparities in survival for patients with solid malignancies having synchronous brain metastases. 2-year survival rates (95% CI). Cancer Groups Low-income High-income Combined Cancers 11% (11-12%) 18% (18-19%) Lung and/or Bronchus 10% (10-11%) 17% (17-18%) Breast 27% (25-29%) 34% (31-37%) Melanoma 19% (17-21%) 23% (20-25%) Kidney and/or Renal Pelvis 15% (13-17%) 18% (15-21%)

Minimal change glomerular disease associated with solid neoplasms: a systematic review.

Paraneoplastic minimal change disease (MCD) has been associated with hematological malignancies, whereas solid malignancies are commonly associated with membranous glomerulonephritis. In this systematic review of the literature, we describe the clinical features, treatment and outcome of MCD associated with solid neoplasms. We performed a systematic review of the MEDLINE, COCHRANE, EMBASE and SCOPUS databases, including case reports of adult patients with biopsy-proven MCD and solid malignancy, without language or time restrictions. Sixty-seven papers were included, presenting 86 cases with a mean age of 57.8 ± 14.7years; 41.0% were women. Nephrotic syndrome was the initial presentation in 96.2% of patients; 67.2% had kidney function impairment, and 21.2% required kidney replacement therapy. The most frequent malignancies were malignant thymoma (34.9%), kidney (14.0%), lung (12.8%), and gastrointestinal tumors (12.8%). In 40.7% of cases, the neoplasm diagnosis preceded MCD by 33.8 ± 46.1months, while in 31.4%, it followed diagnosis ofMCD by 12.4 ± 22.6months. In 27.9%, the neoplasm and kidney disease were diagnosed simultaneously. Immunosuppressive therapy was started in 79.1% of cases and tumor-specific treatment in 83.7%. Remission of MCD was achieved in 80.2% of patients: 38.2% responded to immunosuppressive treatment alone and 29.6% to oncological treatment alone. The association between MCD and solid neoplasms is well-documented. Immunosuppressive therapy alone induced nephrotic syndrome remission in over one-third of cases; most others responded to tumor-specific treatment. Solid tumor screening should be considered in MCD independently of the steroid response, though more data on solid tumor-associated MCD prevalence are needed for a definitive statement. CRD42024521854.

Impact of a trainee-led initiative to address PCP prophylaxis barriers.

319 Background: In a prior trainee-led QI initiative, we surveyed clinicians about Pneumocystis pneumonia (PCP) and assessed rates of appropriate prophylaxis. Through retrospective chart review, we found that 47% of eligible patients (n=140/297) received PCP prophylaxis between 5/2022 and 5/2023. Clinician-reported barriers included knowledge gaps, systems-related gaps, and unclear corticosteroid durations. In the current initiative, we built an order set to facilitate PCP prophylaxis prescription and created an automated approach to assess prophylaxis rates. We then re-evaluated perceived barriers to prescribing PCP prophylaxis. Methods: A multidisciplinary team of oncology fellows and QI staff was established at Johns Hopkins. A new PCP prophylaxis order set was implemented on 4/15/2023. An automated data query was developed to identify patients with solid malignancies who were eligible for PCP prophylaxis per ASCO/IDSA guidelines (≥20mg prednisone equivalents daily for ≥1 month). Patient data was collected between 4/15/2022 and 4/15/2024. Surveys were conducted in 5/2023 and 5/2024 to assess prescriber knowledge of, and attitudes toward, PCP prophylaxis. The survey was open to prescribers across oncology specialties. Results: 1,404 patients were eligible for PCP prophylaxis over the 2-year study period, with 19% (n=264) receiving prophylaxis. In the year before the order set, 21% (n=138) of eligible patients were prescribed prophylaxis. In the year after the order set, 17% (n=126) of eligible patients were prescribed prophylaxis. A survey conducted post order set implementation included 52 responses from 42% (n= 22) attending physicians, 35% (n=18) advanced practice providers, and 23% (n=12) residents/fellows. While 92% (n=48) of survey participants had prescribed PCP prophylaxis, 31% (n=16) knew the dose/duration of corticosteroids at which society guidelines recommend prophylaxis. Unclear corticosteroid duration, guideline knowledge, and concern about side-effects were the most commonly reported barriers to prescribing prophylaxis. Conclusions: Compared to the prior chart review approach, the automated query identified more than twice as many patients at risk for PCP. Strikingly, &lt;25% of eligible patients were prescribed PCP prophylaxis. Prescription rates did not improve following implementation of the order set. However, the post order set survey found increased rates of guideline knowledge and identified unclear corticosteroid durations as the primary barrier to prophylaxis. Building on these findings, an additional PDSA cycle is ongoing including development of notification system alerting providers when PCP prophylaxis is recommended for their patients. Barriers to PCP prophylaxis. Barrier Number of Respondents (%) Pre Order Set Number of Respondents (%) Post Order Set Unclear Corticosteroid Duration 8 (11%) 10 (19%) Guideline Knowledge 11 (16%) 7 (13%) Lack of EMR Notification 6 (9%) 2 (4%)

Methotrexate: Use in the Post Dobbs v. Jackson Era.

Methotrexate is one of the most frequently used medications for the treatment of rheumatic diseases. Although initially developed for use as chemotherapy for both solid and hematologic malignancies, it was used as early as the 1960s with success for rheumatoid arthritis (RA) and psoriatic arthritis, ultimately being approved by the US Food and Drug Administration for the treatment of RA in 1988. Beyond RA and psoriatic arthritis, methotrexate is used in the treatment of systemic lupus erythematosus, idiopathic inflammatory myopathies, and other inflammatory conditions. Methotrexate is cytotoxic to the trophoblast and has been used to treat both ectopic pregnancy and gestational trophoblastic neoplasia, leading to studies in the early 1990s that showed it was effective and safe for early abortion in combination with prostaglandin E1 analog misoprostol. Methotrexate is also a teratogen, causing serious birth defects in 6%-10% of patients taking it while pregnant. Additionally, women are more likely to be affected by both RA at SLE, as compared with males, thus worsening the burden of these adverse effects. Both methotrexate's history of use as an abortifacient and its teratogenic properties make its use more complicated in the current era of abortion policy in the United States following the Dobbs v. Jackson Women's Health Organization ruling. Recently published data suggest that this ruling has affected both provider perspectives and patient experiences as it relates to methotrexate use. In the post-Dobbs era, the role of the rheumatologist as it relates to patients' sexual and reproductive health is likely to expand.

Detection and Interpretation of Clonal Hematopoiesis Variants during Routine Solid Tumor Next-Generation Sequencing: A Single-Institution Experience

Clonal hematopoiesis (CH) and Clonal Cytopenia of Undetermined Significance (CCUS) are recently recognized diagnostic entities that serve as an independent risk factor for cardiovascular disease and myeloid malignancy. CH is an incidental finding and evaluation of the incidence of CH/CCUS associated mutations in solid tumor Next Generation Sequencing (NGS) samples was undertaken to better understand the prevalence of mutations in this population. A retrospective review of clinical sequencing data for solid tumor malignancies diagnosed February 2022-April 2023 on NGS data was performed. Cases were reviewed for variants in genes associated with CH/CCUS. Variant allele frequencies and other factors of the sequencing data were assessed for determining risk of CH/CCUS. 2,479 cases were evaluated during the study period. Of these, 29 cases demonstrated potential CH/CCUS associated mutations with a total of 33 variants identified. These were identified in a variety of tumor types, with gliomas being the most common. Significant cardiac histories were found in over half of cases identified and few cases had abnormal blood counts. Detailed criteria for flagging variants as suspicious for CH and recommend these criteria as future guidelines for reporting are described. These variants are incidental findings which require more extensive follow up or change in therapy management utilizing a single institutional cohort.

Delta‐like ligand 4 inhibitor drug treatment induces pulmonary hypertension in cancer clinical trials

AbstractDelta‐like ligand 4 (DLL‐4) inhibitor drugs are an emerging cancer treatment. In clinical trials for solid organ malignancies, intravenous administration of monoclonal antibodies that inhibit DLL‐4 is associated with development of pulmonary hypertension, in the absence of left ventricular dysfunction. Analysis of 13 clinical trials showed that pulmonary hypertension is a complication of DLL‐4 inhibition.

Biologic therapy in psoriasis patients with current or previous solid tumor malignancy: A systematic review

Biologic therapy in psoriasis patients with current or previous solid tumor malignancy: A systematic review

2 Oral: Preliminary results from SEACRAFT-1: An open-label study of naporafenib with trametinib in patients with locally advanced unresectable or metastatic solid tumor malignancies with RAS Q61X mutations

2 Oral: Preliminary results from SEACRAFT-1: An open-label study of naporafenib with trametinib in patients with locally advanced unresectable or metastatic solid tumor malignancies with RAS Q61X mutations

Taste and smell are associated with dietary intake, eating behavior, nutritional status, and health-related quality of life in children with cancer

Background & aimsSmell and taste changes are frequently reported bothersome treatment symptoms during treatment for childhood cancer and assumed to influence outcomes such as food intake. Since nutritional status of children with cancer is already vulnerable, any detrimental effects on food intake should be prevented. Therefore, understanding the exact relationship between chemosensory changes and dietary intake, eating behavior, and other domains such as health-related quality of life (HRQoL), is important for improving outcomes. MethodsIn this longitudinal study, we followed 87 childhood cancer patients treated for hematological, solid, or brain malignancies. Smell (odor threshold and odor identification) and taste function (total taste score) were objectively investigated using commercial Sniffin’ Sticks and Taste Strips respectively, and by self-report. Dietary intake was measured using a 3-day food dairy. For nutritional status, BMI expressed as standard deviation scores was derived from medical records. Eating behavior and HRQoL were assessed by the Behavioral Pediatrics Feeding Assessment Scale (BPFAS) and PedsQL 4.0 Generic Core Scales, respectively. Measurements were taken approximately 6 weeks (T0), 3 months (T1), 6 months after starting chemotherapy (T2), and 3 months after termination of chemotherapy or maintenance phase for children with acute lymphoblastic leukemia (ALL) (T3). Dietary intake, eating behavior, nutritional status, and HRQoL were modelled over time using mixed model analysis. Associations between smell and taste (objective and self-report), as well as patient characteries were studied. ResultsEnergy intake significantly increased during the study period, with a higher age, BMI, and total taste scores associated to this increase. Boys had higher energy intake compared to girls. Eating behavior scores significantly declined, indicating less eating problems. Age, pre-diagnosis eating behavior, self-reported smell changes, and tube feeding were associated to eating behavior. BMI significantly increased, with a higher BMI at diagnosis to be related to a higher BMI during the study period. A lower BMI was found in children receiving tube feeding and self-reported taste changes. HRQoL improved during the study period, with lower HRQoL in children receiving tube feeding and self-reported taste changes. ConclusionBoth objective and subjective measures of taste and smell influence dietary intake, eating behavior, nutritional status, and HRQoL. Individual dietary advice and coping strategies are warranted to prevent detrimental effects of chemosensory changes on food intake and clinical outcomes in children with cancer.

Race and ethnicity representation in phase 2/3 oncology clinical trial publications in the United States: A systematic review.

20 Background: The five 1997 Office of Management and Budget (OMB) races in the US include American Indian or Alaskan Native (AI/AN), Asian, Black or African American, Native Hawaiian or Other Pacific Islander (NHPI), and White, with Hispanic ethnicity. Despite the Affordable Care Act (ACA) mandating OMB-based collecting/reporting standards, race and ethnicity publishing in medical journals is inconsistent, despite being necessary to achieve health equity. We aimed to quantify race and ethnicity reporting rates and calculate representation quotients (RQs) in published oncology clinical trials. Methods: In this systematic review, PubMed/Embase were queried for phase 2/3 clinical trials of the 6 most common noncutaneous solid malignancies, published between 2012-2022, in 4 high-impact journals. Trial characteristics were recorded. The RQs for each race and ethnicity were calculated by dividing the percent of representation in clinical trial publications by the percent of year-matched, site-specific incident cancers in the US, compared with Kruskal-Wallis tests with Bonferroni Correction (BC). Reporting was compared between journal publications and ClinicalTrials.gov. Results: Among 1,202 publications evaluated, 364 met inclusion criteria: 16 JAMA , 241 JCO , 19 Lancet , and 88 NEJM . Publications included 268,209 patients (171,132 women [64%]), with a median of 356 (IQR, 131-800) patients per publication. Reported race and ethnicity included AI/AN in 52 (14%) publications, Asian in 196 (54%), Black or African American in 215 (59%), Hispanic in 67 (18%), NHPI in 28 (8%), and White in 254 (70%). Median RQ varied across race (P &lt; .001 BC) with 1.04 (IQR, 0.09-4.77) for Asian, 0.98 (IQR, 0.86-1.06) for White, 0.42 (IQR, 0.12-0.75) for Black or African American, and 0.00 (IQR, 0.00-0.00) for both AI/AN and NHPI patients. Sensitivity analyses showed similar findings upon subset analysis for US-only clinical trials. There was significantly less race and ethnicity reporting in the clinical trial publications compared with ClinicalTrials.gov documentation for AI/AN (14% vs 45%, P &lt; .001 per McNemar χ 2 with continuity correction [MC]) and NHPI (7.7% vs 43%; P &lt; .001 MC). Conclusions: While most phase 2/3 oncology clinical trials published in high-impact journals report race and ethnicity, most did not report AI/AN and NHPI racial categories. Our findings support a call to action for consistent journal policies and transparent race and ethnicity reporting, in alignment with ACA-concordant race and ethnicity federal reporting requirements.

Percutaneous Kidney Biopsy in Patients with Metastatic Solid Malignancy and AKI on Systemic Anticancer Therapy

Percutaneous Kidney Biopsy in Patients with Metastatic Solid Malignancy and AKI on Systemic Anticancer Therapy

511LBA (PB-511) LBA Posters: Selective Targeting of Cyclin E1 Using Molecular Glue Degraders in CCNE1 Amplified Solid Malignancies

511LBA (PB-511) LBA Posters: Selective Targeting of Cyclin E1 Using Molecular Glue Degraders in CCNE1 Amplified Solid Malignancies

Phase I/II study of BMS-986156 with ipilimumab or nivolumab with or without stereotactic ablative radiotherapy in patients with advanced solid malignancies

BackgroundBMS-986156 is an agonist of the glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related protein (GITR) and promotes increased effector T-cell activation. Combined anti-GITR, anti-programmed death-1, anti-cytotoxic T-lymphocyte-associated protein 4 antibodies and...

The impact of supervised and home exercise activity intervention on circulating immune cell numbers in cancer patients

IntroductionMalignant diseases challenge clinicians to balance treatment intensity and patient quality of life. Regular physical activity positively impacts mental and physical health, benefiting sleep patterns, heart rate, and overall health. Moreover, telehealth physical exercise training represents a viable option for maintaining intrinsic capacity. The American Cancer Society highlights exercise's role in helping patients cope with anti-cancer treatment side effects. In the Czech Republic, there is no fitness-promoting protocol for cancer patients, despite recognized benefits. Exercise may also enhance immune function, with moderate-intensity exercise potentially positively affecting immune cell counts. ObjectiveThis study aimed to analyze the long-term effects of exercise on circulating immune cells in patients undergoing treatment for solid malignancies. Patients and methods49 participants were recruited at the Masaryk Memorial Cancer Institute, Czech Republic, starting September 2021. Participants were randomized into an experimental (SAPA = undergoing monitored exercise program) group (N = 16; madian age: 46,6; median BMI: 25,1) and a control (CO) group (N = 33; madian age: 52,0; median BMI: 25,3). Flow cytometry was used to examine cellular immunological profiles. The exercise program involved thrice-weekly sessions conducted online. ResultsSAPA group showed stable lymphocyte counts post-exercise (percentage chance: +0,5 %; p = 0,256; effect size r = −0,284), while the CO group exhibited a significant drop (percentage chance: −23,0 %; p = 0,015; effect size r = −0,423). B lymphocyte numbers were significantly higher in the SAPA group post-exercise compared to the CO group (p = 0,003; effect size r = −0,422). The number of Th-lymphocytes, T-c lymphocytes, T-gamma/delta lymphocytes, and NK cells remained stable in SAPA but dropped in CO group. ConclusionExercise's impact on the immune system in cancer patients shows promise, with differences noted between acute and chronic exercise effects. Previous studies on acute exercise indicate a rise in immune cell counts, supporting our findings of stable or increased immune cells with controlled exercise in cancer patients. Controlled physical activity stabilizes or increases certain immune cell populations in patients undergoing chemotherapy for solid malignancies, highlighting the potential benefits of incorporating exercise into cancer treatment protocols.

Integrating IL-12 mRNA nanotechnology with SBRT eliminates T cell exhaustion in preclinical models of pancreatic cancer

Pronounced T cell exhaustion characterizes immunosuppressive tumors, with the tumor microenvironment (TME) employing multiple mechanisms to elicit this suppression. Traditional immunotherapies, such as immune checkpoint blockade, often fail due to their focus primarily on T cells. To overcome this, we utilized a proinflammatory cytokine, IL-12, that re-wires the immunosuppressive TME by inducing T cell effector function while also repolarizing immunosuppressive myeloid cells. Due to toxicities observed with systemic administration of this cytokine, we utilized lipid nanoparticles encapsulating mRNA encoding IL-12 for intratumoral injection. This strategy has been proven safe and tolerable in early clinical trials for solid malignancies. We report an unprecedented loss of exhausted T cells and the emergence of an activated phenotype in murine pancreatic ductal adenocarcinoma (PDAC) treated with stereotactic body radiation therapy (SBRT) and IL-12mRNA. Our mechanistic findings reveal that each treatment modality contributes to the T cell response differently, with SBRT expanding the TCR repertoire and IL-12mRNA promoting robust T cell proliferation and effector status. This distinctive T cell signature mediated marked growth reductions and long-term survival in local and metastatic PDAC models. This is the first study of its kind combining SBRT with IL-12mRNA and provides a promising new approach for treating this aggressive malignancy.