Advanced Metastatic Disease Research Articles

Trends in Management of Malignant Bowel Obstructions: A Longitudinal Analysis of the National Inpatient Sample.

Malignant bowel obstructions (MBO) are complex, heterogeneous disease processes which can be managed with surgical or endoscopic interventions. Patients with MBO often have advanced metastatic disease and poor functional status, which makes it difficult for providers to determine the best treatment strategy. Patients with urgent or emergent admissions and a primary or secondary ICD-9/ICD-10 diagnosis of bowel obstruction with an additional diagnosis of disseminated cancer were identified from the National Inpatient Sample (2000-2017). Patients were stratified into operative and non-operative intervention groups. Multivariate regression determined factors associated with surgical treatment of MBO based on significant factors on univariate analysis. Trends in treatment over time were calculated using log-linear regression to determine the annual percent change (APC). Of 1118 patients, 18% underwent surgery and 7% underwent endoscopic intervention. From 2000 to 2017, a decreasing proportion of patients underwent surgery (APC -2.4, p = 0.023) with a commensurate increase in endoscopic interventions (APC 5.3, p = 0.042). There was also a decrease in the proportion of patients who died during hospitalization (APC -4.3, p = 0.029). Surgery was associated with longer mean lengths of stay (13 days vs. 7 days, p < 0.001) and higher rates of in-hospital mortality (13% vs. 6%, p = 0.001) compared to non-operative management. The proportion of patients receiving surgery for MBO is decreasing and that receiving endoscopic interventions is increasing. In-hospital mortality is also decreasing proportionately, suggesting an improvement in patient selection.

Denosumab combined with radiotherapy as an alternative to surgery for advanced metastatic bone lesions and pathologic fractures: a retrospective case study of 38 patients

Background and purpose: Pathologic and impending fractures occur in patients with advanced metastatic disease and necessitate surgical interventions with high risk of complications. The aim of this study was to analyze the efficacy of combined treatment with denosumab and radiotherapy as an alternative to surgery in treating bone metastases of the pelvis and extremities. Methods: This retrospective cohort study included 38 patients with impending and pathologic fractures due to carcinoma metastases who received monthly injections of denosumab (120 mg/dose) and radiotherapy. Twenty-three patients received denosumab and single-dose radiotherapy of 8 Gy, and 15 patients received denosumab and fractionated radiotherapy. We assessed pain, radiographic signs of fracture healing, survival and complications. Results: Of the 38 patients 36 experienced pain reduction. Callus formation was observed in 11/17 patients with pathologic fractures, and increased mineralization was found in 12/21 patients with impending fractures. In 23/38 patients, we found both pain reduction and callus formation or increased mineralization. There were no statistically significant differences in treatment outcomes between the patients who received denosumab and single-dose radiotherapy and those who received denosumab and fractionated radiotherapy. The survival rates at 30 days and 1 year were 95% and 56%, respectively. Interpretation: Combined treatment with denosumab and radiotherapy may reduce pain and promote bone healing in patients with metastatic impending and pathologic fractures. In this combined treatment, the effect of single-dose radiotherapy appears to be comparable to that of fractionated regimens

Percutaneous Pulmonary Valve Implantation With Self‐Expanding Valves for Carcinoid Heart Diseases

ABSTRACTCarcinoid heart disease is an important complication of neuroendocrine tumors that may lead to significant morbidity and mortality. Right‐sided heart valve involvement with consequent valve dysfunction is one of the common manifestations. Patients often have multiple, significant comorbidities with advanced metastatic disease and, as such, may not be suitable for surgical valve replacement due to excessive risk. Transcatheter valve replacement using balloon‐expandable valves has been the mainstay of management for these patients, particularly with stenotic lesions but there is limited experience in patients with pulmonary regurgitation and dilated pulmonary arteries outside the dimensions that would be suitable for these valves. We report three successful cases of percutaneous pulmonary valve implantation with the VenusP‐valve, a large self‐expanding valve platform, and highlight the technical aspects and challenges specific to treatment of pulmonary regurgitation in patients with carcinoid heart disease. Percutaneous pulmonary valve implantation, using the VenusP‐valve, may be considered an effective treatment in this patient group.

Enhancing Anti-PD-1 Immunotherapy by Targeting MDSCs via Hepatic Arterial Infusion in Breast Cancer Liver Metastases.

Surgery, chemotherapy, and radiation often have limited utility for advanced metastatic disease in the liver, and despite its promising activity in select cancers, PD-1 blockade therapy similarly has minimal benefit in this setting. Curaxin, CBL0137, is an experimental anti-cancer drug that disrupts the binding of DNA to histones, destabilizes chromatin, and induces Z-DNA formation which may stimulate anti-tumor immune responses. Murine cell lines of colon (CT26) and breast (4T1) cancer were interrogated for survival and CBL0137-associated DNA changes in vitro. Immunocompetent models of liver metastases followed by CBL0137 hepatic arterial infusion (HAI) were used to examine in vivo tumor cell DNA alterations, treatment responses, and the immune contexture associated with CBL0137, both alone and in combination with anti-PD-1 therapy. CBL0137 induced immediate changes to favor tumor cell death in vitro and in vivo with an efficient tumor uptake via the HAI route. Toxicity to CBL0137 was minimal and anti-tumor treatment effects were more efficient with HAI compared to intravenous delivery. Immune effects were pronounced with CBL0137 HAI with concurrent depletion of a specific population of myeloid-derived suppressor cells and maintenance of effector T cell populations. Combination of CBL0137 HAI with PD-1 blockade improved survival in 4T1 tumors but not in CT26 tumors, and therapeutic efficacy relies on the finding of simultaneous and targeted depletion of myeloid-derived suppressor cells and skewing of T cell populations to produce synergy with PD-1 blockade therapy.

Cancer Therapy-Induced Encephalitis.

Encephalitis associated with cancer therapies is a rare but serious complication that can significantly impact patients' quality of life and it requires prompt identification and management. Over the past two decades, immunotherapy-particularly immune checkpoint inhibitors-has become a cornerstone of cancer treatment, with up to half of metastatic cancer patients in economically developed countries now receiving these therapies. The widespread adoption of immunotherapy has led to improved survival rates and long-term remissions, even in patients with advanced metastatic disease. However, as immune modulators, these therapies can trigger a range of immune-related adverse events, including a variety of novel neurological toxicities. Among these, encephalitis is of particular concern due to its potential severity, which can compromise treatment outcomes. This review aims to provide a comprehensive overview of the literature on this condition, highlighting optimal diagnostic strategies and management approaches to mitigate the risk of significant morbidity, while also comparing encephalitis induced by immunotherapy with that caused by traditional chemotherapies and targeted oncologic treatments.

Theranostics, Advanced Cancer, and The Meaning of Life.

There is an unmet need to recognize and address the psychosocial and spiritual support of the rapidly growing population of cancer survivors living with advanced metastatic disease which is essentially incurable. Palliative chemotherapy may do more harm than good. The role of the physician in the provision of a supportive, compassionate relationship of mutual trust is critical in the exploration of spirituality and the meaning of life for each individual patient. The objective must be to enhance quality of life rather than prolong it at any cost. Nuclear physicians are now equipped to offer effective control of advanced metastatic cancer of prostate and neuroendocrine neoplasms without clinically evident toxicity. They also now have the potential to practice phronesis, and in so doing, to significantly ameliorate the quality of life of patients afflicted with these specific advanced cancers. During the time of prolonged symptom-free survival, these patients may be encouraged to find life's meaning and a peaceful acceptance of their inevitable demise.

ESR Essentials: role of PET/CT in neuroendocrine tumors-practice recommendations by the European Society for Hybrid, Molecular and Translational Imaging.

Neuroendocrine neoplasms (NEN) originate from the secretory cells of the neuroendocrine system, with the majority arising in the gastrointestinal tract and pancreas. Given the heterogeneity in the biological behavior and morphological differentiation of these tumors, advanced imaging techniques are crucial for supporting the suspected diagnosis, accurate staging, and monitoring therapy. As most well-differentiated NEN demonstrate overexpression of somatostatin receptors (SSR) on the cell surface, SSR-directed PET/CT is considered the reference standard for imaging of this particular entity. SSR-PET/CT should be the imaging method of choice in every NEN G1 or G2 and considered for re-staging after both potentially curative and non-curative surgeries. The extent of SSR expression is also crucial for determining a patient's eligibility for peptide receptor radionuclide therapy (PRRT). PRRT utilizes [177Lu]Lu-DOTA-TATE to target the SSR receptor and can significantly prolong progression-free survival in patients with advanced, progressive neuroendocrine tumor of the gastroenteropancreatic system (GEP-NET). PET/CT is a central component of the multidisciplinary management of NEN. Variable follow-up intervals are recommended, considering that tumors with higher proliferation rates or advanced metastatic disease require more frequent assessments. The combination with other imaging modalities, like MRI, complements SSR-PET/CT, further enhancing overall diagnostic accuracy. KEY POINTS: Somatostatin receptor-PET/CT (SSR-PET/CT) is the guideline-recommended reference standard for imaging well-differentiated neuroendocrine tumors (NET). SSR-PET/CT should be the diagnostic imaging of choice for staging and post-therapy re-staging of grade 1 or 2 NET (G1 or G2). Variable follow-up intervals are recommended for NET G1 and G2. Tumors with higher proliferation rates or advanced metastatic disease necessitate more frequent assessments.

OTHR-12 INCIDENCE, CLINICAL PRESENTATION, MANAGEMENT AND ONE- AND TWO-YEAR SURVIVAL OF PATIENTS WITH MEDULLOBLASTOMA AT INKOSI ALBERT LUTHULI CENTRAL HOSPITAL, KWAZULU NATAL PROVINCE: A TEN YEAR REVIEW

Abstract OBJECTIVE Epidemiology, clinical presentation, stage and multidisciplinary treatment modalities for Medulloblastoma (Mb) at Inkosi Albert Luthuli Central Hospital (IALCH) for the 10 year period from 2003 to 2012. It also evaluated the 1 and 2 year survival rate. Methodology: Single center- retrospective study of Mb patients below the age of 18 years in a low and middle income country (LMIC) setting. RESULTS The 30 patients included in the study, median age was 9 years. Male to female ratio of 1.3:1. 70% were black race. Average incidence was 14 per 1000 children years. Headache was most common symptom in 70% of the patients. Majority presented with advanced non metastatic disease (T3b). All patients had shunt insertion prior to debulking surgery and 60% had gross total resection. More than half of the cases had reduced dose irradiation (30.6Gy) to the cranial and spinal compared to 36% who had 36Gy. 96% received concurrent vincristine with radiotherapy. 89.7% received adjuvant chemotherapy and 82.8% completed 6 cycles. There was not enough data to determine any trends in the different modalities of treatment offered over the period of 10 years. One year survival rate was 83.33% [95% CI 64.55; 93.70%] and probability of surviving two years was 80.00% [95% CI 60.87%; 91.60%]. CONCLUSION Children present with advanced stages requiring multi-level surgeries. Dedicated multi-disciplinary approach to treatment conferred decent survival outcomes despite the advanced stages at presentation. Similar successes were reflected in the only other study on the subject in Cape Town in a 3 decade retrospective study between the years 1985-2005. These studies highlight the importance of implementing multidisciplinary team management in parallel with modern radiotherapy techniques to improve survival for children with medulloblastoma. Current training programs like Access to Care Capetown could further improve the outcome in countries establishing or transitioning to new radiotherapy techniques.

Characterization of circulating tumor cells in patients with metastatic bladder cancer utilizing functionalized microfluidics

Assessing the molecular profiles of bladder cancer (BC) from patients with locally advanced or metastatic disease provides valuable insights, such as identification of invasive markers, to guide personalized treatment. Currently, most molecular profiling of BC is based on highly invasive biopsy or transurethral tumor resection. Liquid biopsy takes advantage of less-invasive procedures to longitudinally profile disease. Circulating tumor cells (CTCs) isolated from blood are one of the key analytes of liquid biopsy. In this study, we developed a protein and mRNA co-analysis workflow for BC CTCs utilizing the graphene oxide (GO) microfluidic chip. The GO chip was conjugated with antibodies against both EpCAM and EGFR to isolate CTCs from 1 mL of blood drawn from BC patients. Following CTC capture, protein and mRNA were analyzed using immunofluorescent staining and ion-torrent-based whole transcriptome sequencing, respectively. Elevated CTC counts were significantly associated with patient disease status at the time of blood draw. We found a count greater than 2.5 CTCs per mL was associated with shorter overall survival. The invasive markers EGFR, HER2, CD31, and ADAM15 were detected in CTC subpopulations. Whole transcriptome sequencing showed distinct RNA expression profiles from patients with or without tumor burden at the time of blood draw. In patients with advanced metastatic disease, we found significant upregulation of metastasis-related and chemotherapy-resistant genes. This methodology demonstrates the capability of GO chip-based assays to identify tumor-related RNA signatures, highlighting the prognostic potential of CTCs in metastatic BC patients.

Future Treatment Strategies for Cancer Patients Combining Targeted Alpha Therapy with Pillars of Cancer Treatment: External Beam Radiation Therapy, Checkpoint Inhibition Immunotherapy, Cytostatic Chemotherapy, and Brachytherapy.

Cancer is one of the most complex and challenging human diseases, with rising incidences and cancer-related deaths despite improved diagnosis and personalized treatment options. Targeted alpha therapy (TαT) offers an exciting strategy emerging for cancer treatment which has proven effective even in patients with advanced metastatic disease that has become resistant to other treatments. Yet, in many cases, more sophisticated strategies are needed to stall disease progression and overcome resistance to TαT. The combination of two or more therapies which have historically been used as stand-alone treatments is an approach that has been pursued in recent years. This review aims to provide an overview on TαT and the four main pillars of therapeutic strategies in cancer management, namely external beam radiation therapy (EBRT), immunotherapy with checkpoint inhibitors (ICI), cytostatic chemotherapy (CCT), and brachytherapy (BT), and to discuss their potential use in combination with TαT. A brief description of each therapy is followed by a review of known biological aspects and state-of-the-art treatment practices. The emphasis, however, is given to the motivation for combination with TαT as well as the pre-clinical and clinical studies conducted to date.

Did the Coronavirus Disease 2019 (COVID-19) Pandemic Cause a Delay in the Diagnosis of Breast Cancer Patients?

Introduction The coronavirus disease 2019 (COVID-19) outbreak, first reported in Wuhan, China, in December 2019, quickly hit the world in just one month, causing a global public health emergency. We aimed to investigate whether the COVID-19 pandemic caused a delay in the hospital admissions of breast cancer patients and diagnosis of breast cancer, thus increasing the tumor size and the stage of the disease. Materials and methods Included in the study were patients who underwent breast cancer surgery between 01/03/2019 and 01/03/2020 (pre-COVID-19, first period) and between 01/03/2020 and 01/03/2021 (post-COVID-19, second period). Three hundred and seventy patients with enough details were included, and details were analyzed retrospectively. Tumor characteristics of pre-COVID-19 breast cancer patients were compared with the tumor characteristics of post-COVID-19 breast cancer patients. Demographics, preoperative diagnosis, tumor properties, surgical procedure (breast-conserving surgery, modified radical mastectomy, simple mastectomy, skin-sparing mastectomy), tumor size, total lymph node number, metastatic lymph node number, locally advanced disease, metastatic disease, and neoadjuvant therapy were evaluated. Results The mean tumor size increased significantly in the post-COVID-19 primary surgery group (p=0.005). There is no significant relationship between the pre-COVID-19 and post-COVID-19 period and pT in the neoadjuvant received group (p>0.05). The presence of pT2+pT3+pT4 was statistically significantly higher in the post-COVID-19 primary surgery group (p=0.001). The mean value of metastatic lymph nodes dissected between pre-COVID-19 and post-COVID-19 primary surgery groups increased significantly (p=0.010). Pericapsular extension was higher in the post-primary surgery group (p=0.002). Conclusion During the COVID-19 outbreak, breast cancer patients have difficulty accessing healthcare services and hesitate to apply to hospitals to fear contracting the COVID-19 disease. This situation has led to delays in diagnosing breast cancer patients, increased tumor size and pT grade, increased number of metastatic lymph nodes, pericapsular extension, and the resulting disease often appearing in advanced sizes and stages.

Systemic Management of Advanced Adrenocortical Carcinoma.

Adrenocortical cancer (ACC) is a rare and aggressive disease. Surgery has traditionally been the primary treatment for locally advanced disease with ongoing controversy around the optimal neoadjuvant and adjuvant treatment options. Unfortunately, local recurrence and the eventual development of metastatic disease is common and five-year survival rates are poor. While many trials have evaluated novel systemic agents to treat advanced adrenocortical cancer, only a few drugs have demonstrated any response at all. To date, only one drug, mitotane, is approved in the US for ACC and no regimen has clearly shown an increase in overall survival. In advanced metastatic or unresectable disease, data supports the first line regimen of EDP chemotherapy + mitotane as the primary treatment modality. In the second line, while data is limited, we would recommend consideration of immunotherapy using a PD(L)1 agent combined with a TKI/VEGF inhibitor or combination immunotherapy with PD1/CTLA-4 drugs. In all cases, we always prefer a clinical trial as available. This article reviews data from multiple studies evaluating novel systemic agents against ACC and discusses current systemic therapy combinations and ongoing clinical trials.

Non-Small-Cell Lung Cancer Patients Harboring ROS1 Rearrangement: Real World Testing Practices, Characteristics and Treatment Patterns (ROS1REAL Study).

ROS1 rearrangements are considered rare in non-small-cell lung cancer (NSCLC). This retrospective real-world study aimed to evaluate first-line treatment with crizotinib, a tyrosine kinase inhibitor (TKI) standard of care vs. new generation ROS1 anti-cancer agents. Forty-nine ROS1-expressing NSCLC patients, diagnosed with advanced metastatic disease, were included. Molecular profiling using either FISH/CISH or NGS was performed on tissue samples. Twenty-eight patients were treated with crizotinib, while fourteen patients were administered newer drugs (entrectinib, repotrectinib) and seven patients received platinum-doublet chemotherapy in a first-line setting. Overall response rate and disease control rate for the crizotinib and entrectinb/repotrectinib cohort were 68% and 82% vs. 86% and 93%, respectively. Median progression free survival was 1.6 years (95% CI 1.15-2.215) for the crizotinib treatment vs. 2.35 years for the entrectinib/repotrectinib cohort (95% CI 1.19-3.52). Central nervous system progression was noted in 20% and 25% of the crizotinib and entrectinib/repotrectinib cohorts, respectively. This multi-center study presents real-world treatment patterns of ROS1 NSCLC population, indicating that crizotinib exhibited comparable results to entrectinib/repotrectinib in a first-line setting, although both response rate and survival was numerically longer with treatment with newer agents.

Disparities in the prevalence of anxiety and major depressive disorder in patients with lung cancer and the associated risk factors: A retrospective analysis.

e22544 Background: Cancer is a leading cause of mortality and has been associated with an increasing prevalence of psychological disorders. Previous studies indicate that approximately 1 in 8 individuals diagnosed with lung cancer also experience symptoms of depression. Our study aimed to assess the disparities in the prevalence and association of Anxiety and Major depressive disorder (MDD) in lung cancer patients. Methods: Using the National Inpatient Sample 2017-2020, we identified lung cancer patients with regional and advanced metastatic disease. They were divided into two groups - with and without concomitant Anxiety and MDD. Baseline demographic characteristics were analyzed to assess disparities in prevalence, and multivariate logistic regression was used to evaluate the association of Anxiety and MDD in these patients. Results: A total of 461975 patients had lung cancer, and 25780(5%) had concurrent diagnoses of Anxiety and MDD. The anxiety + MDD group had 70% females and 30% males (p &lt; 0.001).Females had an increased likelihood of MDD + Anxiety (OR = 2.36 (2.21-2.52); p &lt; 0.001). Compared to younger patients, older patients were less likely to have MDD + Anxiety ( &gt; 65: OR = 0.45(0.25-0.81); p = 0.008). Compared to the white population, patients of other races had a decreased likelihood of MDD + Anxiety (Black: OR = 0.41( 0.36-0.47), p &lt; 0.001; Hispanic: OR = 0.65( 0.55-0.77), p &lt; 0.001; Other races OR = 0.60(0.48-0.76), p &lt; 0.001). Private insurance and patients without insurance were less likely to have MDD + Anxiety (OR = 0.74(0.67-0.81) and OR = 0.56(0.44-0.71), p &lt; 0.001, respectively). Patients admitted to teaching and large hospitals had an increased likelihood of MDD + Anxiety compared to smaller and nonteaching hospitals (OR = 1.13(1.03-1.24), p = 0.006 and OR = 1.14(1.03-1.25), p = 0.007, respectively). Patients with Hyperlipidemia, Hypertension, COPD, and Obesity were more likely to have MDD + Anxiety (OR = 1.39(1.30-1.48), p &lt; 0.001; OR = 1.11(1.03-1.18), p = 0.002; OR = 1.29(1.21-1.38), p &lt; 0.001 and OR = 1.33(1.22-1.45), p &lt; 0.001 respectively). In contrast, patients with Diabetes had a decreased likelihood of concomitant Anxiety + Depression (OR = 0.92(0.85-0.99), p = 0.04). Lung cancer patients with concurrent Anxiety + MDD had a higher total cost of hospitalization. (+$ 2611(66-5156); p = 0.04). Conclusions: Female lung cancer patients and white individuals had an increased risk of anxiety and depression. Patients with private insurance had decreased risk, and those admitted to larger and teaching hospitals had increased association with these psychological disorders. Devising comprehensive strategies to effectively control underlying psychiatric conditions is crucial for improving outcomes in lung cancer patients, aiming to enhance quality of life and prolong life expectancy.

Disparities in the prevalence of acute pulmonary embolism in patients with ovarian cancer: A nationwide analysis.

e17560 Background: Ovarian cancer is the leading cause of death among gynecological cancers. It is highly thrombogenic and is associated with increased venous thromboembolism events. We conducted a retrospective analysis to study the prevalence and disparities in the association of Acute Pulmonary embolism(PE) with ovarian cancer. Methods: National Inpatient Sample (2017-2020) was used to identify the patients with primary diagnosis of Acute PE and was stratified into those with and without concurrent diagnosis of Ovarian cancer ( regional and advanced metastatic disease). Basic demographic variables were analyzed to identify disparities in the prevalence of Acute PE among ovarian cancer patients.Multivariate logistic regression analysis was conducted to examine the association between Acute PE and Ovarian cancer. Results: A total of 651435 patients were hospitalized with a primary diagnosis of Acute PE, and 2980 (0.46%) had a secondary diagnosis of Ovarian cancer. The ovarian cancer group had a greater percentage of white (73.4% vs.71.93%), Hispanics (7.98% vs. 6.04%), and fewer Black patients (15.78% vs. 19.86), p=0.021. Compared to the white, Black population with ovarian cancer (OR=0.77(0.6-0.9); p=0.04) had a decreased likelihood of developing Acute PE without any difference noted in the Hispanics (OR=1.13 (0.81-1.58); p=0.44) and other races (OR=1.11 (0.67-1.83); p=0.67). Patients in the high income groups were more likely to be admitted due to acute PE ($65,000-$85,999: OR=1.35 (1.05-1.73), p=0.018; &gt;$86,000: OR=1.24 (1.14-1.62), p=0.01). A greater percentage of patients with ovarian cancer had private insurance (35.2% vs. 28.91%), while a greater percentage of patients without ovarian cancer had Medicare (54.38% vs. 50.34%) and Medicaid (11.9% vs. 12.5%), p=0.003. Patients with private insurance were more likely to be admitted due to acute PE (OR=1.73(1.36-2.22); p&lt;0.001). Patients with a Charlson comorbidity index of 3 or more had higher odds of Acute PE (OR=1.3(1.12-3.4); p=0.02). A greater percentage of Acute PE patients with ovarian cancer were admitted to large (54.03% vs. 47.86%; p=0.014), urban (95.3% vs. 90.35%; p&lt;0.001), and teaching hospitals (79.87% vs. 69.15%; p&lt;0.001). Teaching hospitals had higher odds of admissions due to acute PE in ovarian cancer patients (OR=1.37(1.07-1.75); p=0.01). On multivariate regression analysis, Ovarian cancer patients had higher odds of Acute PE (OR=1.88 (1.73-2.05); p&lt;0.001). Conclusions: Ovarian cancer patients with Black race and private insurance showed a significantly increased likelihood of admissions due to acute pulmonary embolism. Additionally, urban and teaching hospitals demonstrated higher odds of encountering cases of acute pulmonary embolism. Further prospective studies are necessary to validate the findings presented in our study.

Understanding the relationship between obesity and in-hospital outcomes in gastric cancer patients : A nationwide analysis.

e16050 Background: Gastric cancer is the fifth most common form of cancer and the third leading cause of cancer-related deaths worldwide. Obesity has been identified as a significant risk factor for gastric cancer, associated with increased incidence and heightened complications in hospitalized patients. Our analysis comprehensively evaluates obesity's impact on hospital-admitted gastric cancer patients. Methods: Using the National Inpatient Sample (NIS) 2020, we identified gastric cancer patients with regional and advanced metastatic disease, and they were stratified into patients with and without obesity. The primary outcome was mortality, and secondary outcomes included length of stay, the total cost of hospitalization, and other in-hospital adverse outcomes. Multivariate logistic regression analysis was used to calculate the outcomes after adjusting for confounding variables. Results: A total of 17560 patients were hospitalized with gastric cancer, among which 1720(9.8%) had the concurrent diagnosis of Obesity. The mean age of patients with and without Obesity was 63 (+/- 13.88) and 66 (+/- 12.93),p&lt;0.001 respectively. The obese category had the greater percentage of male patients as compared to females (58.14% vs 44.85% respectively, p&lt;0.001). After adjusting for confounding variables, Obesity was not considered as an independent predictor of mortality in patients with gastric cancer (OR=1.06(0.59-1.92); p=0.90). However, patients with Obesity had prolonged length of stay (+ 1.52 days(1.49-2.26); p=0.004) and total cost of hospitalization (+ $30977(12320-49633); p=0.001). Similarly, obese patients had an increased likelihood of Acute kidney injury (OR=1.47(1.09-1.96); p=0.01), ICU admission (OR=2.01(1.30-3.09); p=0.002), invasive (OR=2.14(1.29-3.54); p=0.003) Noninvasive mechanical ventilation (OR=5.36(2.17-13.14); p&lt;0.001) and Heart failure (OR=1.68(1.09-2.57); p=0.02). No difference was noted in the risk of cardiac arrest (OR=1.26(0.28-5.68); p=0.76), and sepsis(OR=1.76(0.99-3.13); p=0.05). Conclusions: Obesity in patients with gastric cancer is not an independent predictor of mortality but is associated with increased length of stay, the total cost of hospitalization, increased risk of mechanical ventilation, and ICU admissions. Management of obesity can prove crucial in averting a wide range of potential health complications and significantly enhancing the overall quality of life in gastric cancer patients. [Table: see text]

How febrile neutropenia affects hospitalization in patients with bladder cancer: Nationwide insights.

e16625 Background: Bladder cancer is the most prevalent form of malignancy in the urinary tract and is a leading global health concern. Febrile neutropenia is a severe and potentially life-threatening complication of cancer treatment, and limited research exists on the impact of Febrile Neutropenia in bladder cancer. Our study examined its effects on adverse outcomes for hospitalized bladder cancer patients. Methods: The National Inpatient Sample (2017-2020) was employed to identify Bladder cancer patients with regional and advanced metastatic disease as the primary diagnosis and were stratified based on the presence or absence of a secondary diagnosis of Febrile neutropenia (FN). The primary outcome measure was mortality, while the secondary outcomes included length of stay, total cost of hospitalization, and other adverse in-hospital outcomes. Multivariate regression analysis was used to adjust for the confounding variables. Results: A total of 102,485 patients were hospitalized for Bladder cancer, among whom 865 had concurrent FN. The mean age of patients with FN was 67.31±17.44, while that of patients without FN was 72.19±11.48, p&lt;0.001. As compared to Patients without FN, those with FN had a greater percentage of patients with Medicaid (8.77% vs. 6.15%) and private insurance (30.41% vs. 19.74%), while fewer patients with Medicare (58.48% vs. 72.17%), p=0.001. After multivariate regression analysis, patients with FN had increased odds of mortality (OR=4.33,(2.52-7.45); p&lt;0.001). FN patients had a longer length of stay (+2.69 days (1.32-4.05); p&lt;0.001) and higher total cost of hospitalization (+$23,229(3,907-4,255); p&lt;0.001). Patients with FN were more likely to have fluid and electrolyte disorders (OR=1.57(1.11-2.20); p=0.009). However, no significant differences were observed in the odds of Sepsis (OR=1.34(0.62-2.85); p=0.45), Acute kidney injury (OR=1.10 (0.74-1.63); p=0.61), Acute respiratory failure (OR=1.11(0.50-2.50); p=0.78) and ICU admission (OR=0.56(0.20-1.57); p=0.27) between the two groups. Conclusions: In patients with bladder cancer, febrile neutropenia has been identified as an independent predictor of mortality. It is associated with increased healthcare resource utilization and fluid and electrolyte disorders. Proactive management of risk factors can help control febrile neutropenia and reduce the occurrence of adverse events in patients hospitalized with bladder cancer. [Table: see text]

Phase 2/3 study of livmoniplimab in combination with budigalimab in patients with locally advanced or metastatic hepatocellular carcinoma.

TPS4190 Background: Most patients with hepatocellular carcinoma (HCC) present with advanced unresectable or metastatic disease and survival rates remain poor. While approved checkpoint inhibitor (CPI)-based combination regimens for HCC have shown improvements in overall survival (OS), not all patients respond to currently available CPI-based therapy, and new strategies to overcome CPI-resistance using novel combination therapies are urgently needed. HCC gene expression profile analysis points to TGF-β signaling as a possible mechanism of immune escape. The first-in-class humanized monoclonal antibody livmoniplimab (ABBV-151) was developed that specifically binds to the glycoprotein-A repetitions predominant-transforming growth factor (GARP–TGF)-β complex, blocking release of active TGF-β1 and promoting immunoreactivity. A phase 1 study in HCC showed an overall response rate (ORR) of 42% (5/12) when combining livmoniplimab with the programmed cell death 1 inhibitor budigalimab (ABBV-181). We describe herein a phase 2/3 study of livmoniplimab + budigalimab in patients with locally advanced or metastatic HCC. Methods: This multicenter, phase 2/3, randomized, open-label study (NCT06109272) will enroll patients (≥18 years) with advanced HCC (aHCC) who have not previously received systemic treatment and have Barcelona Clinic Liver Cancer stage B or C, not eligible for locoregional therapy, Child-Pugh class A or B7, and Eastern Cooperative Oncology Group performance status 0‒1. The study will have 2 stages. Stage 1 is a phase 2 dose-optimization lead-in, during which ~80 patients will be enrolled and randomized 1:1:2 to receive 1 of 2 doses of livmoniplimab in combination with budigalimab Q3W, or investigator’s choice of either atezolizumab + bevacizumab Q3W or single-dose tremelimumab + durvalumab Q4W per STRIDE regimen. The primary objective of stage 1 is to select the optimal livmoniplimab dose to use in combination with budigalimab. Efficacy, safety, pharmacokinetic (PK), and pharmacodynamic data will be combined with prior phase 1/2 study data to select the livmoniplimab dose for stage 2. Stage 2 is a phase 3 study in ~580 patients with aHCC. Patients will be randomized 1:1 to receive the optimized dose of livmoniplimab + budigalimab or single-dose tremelimumab (300 mg) + durvalumab (1500 mg) Q4W (STRIDE). The primary objective for stage 2 is to evaluate the efficacy of livmoniplimab + budigalimab as measured by median OS. Secondary objectives include assessment of safety, tolerability, immunogenicity, and PK, efficacy measured by median progression-free survival, ORR, and duration of response as well as the impact on patient-reported outcomes. Enrollment is planned in Europe, Asia, and USA, and is open as of Dec 2023. Clinical trial information: NCT06109272 .

Real-world data of efficacy and safety of denosumab on patients with breast cancer with bone metastasis: Results from Chinese clinical experience.

e13103 Background: Bone is the most common metastasis site in advanced metastatic breast cancer disease. Denosumab is advocated by various guidelines with high-quality of evidence for the treatment of breast cancer patients with bone metastases (BM) to delay or reduce the occurrence of skeletal related events (SRE). Data for bone lesion repair after treatment on image is still needed in real world. This retrospective study aims to evaluate the efficacy of denosumab on breast cancer with BM by MD Anderson (MDA) criteria which is specific to BM and its safety in real world. Methods: Data of patients age ≥18 years diagnosed with advanced breast cancer with BM and treated with denosumab from June 1st 2020 to Dec 31st 2022 were retrospectively analyzed. The primary endpoint was the objective response rate (ORR) for bone lesions by MDA criteria in evaluable patients. Secondary endpoints include disease control rate (DCR) for bone lesions, risk of SRE occurrence and safety in total population. Subgroup analysis investigated the impact of the time of denosumab treatment initiation post-diagnosis of BM as well as the duration of treatment with denosumab on efficacy. Comparative analysis was performed using Chi-squared test and a p value of &lt;0.05 was considered statistically significant. Results: Atotal of 185 patients were enrolled with median age of 52.45 (SD: 12.02) years. The median follow-up time was 25.2 months. 49 out of the 130 evaluable patients achieved partial response, resulting in an ORR of 37.69% (95% CI: 0.29-0.47), and a DCR of 90% (95% CI: 0.84-0.95). 16 out of 185 (8.65%) patients developed SRE after denosumab treatment with the median time to the first occurrence of SRE not reached. The ORR and DCR for bone lesions of starting denosumab after diagnosis of BM in ≤3 months vs. &gt;3 months were 31.54% vs. 6.15% (p&lt;0.001) and 68.46% vs. 21.54% (p&lt;0.001), respectively. The ORR and DCR for bone lesions of the duration of denosumab treatment &lt;6 months vs. ≥6 months were 4.62% vs. 33.08% (p&lt;0.001) and 37.69% vs. 76.92% (p&lt;0.001), respectively. Renal function impairment decreased from 33 patients before treatment to 8 patients post-treatment, while hypocalcemia increased from 1.62% to 11.35%. Osteonecrosis of the jaw occurred in one patient (1/185,0.54%) post-treatment. Conclusions: Denosumab was found to be effective and safe for breast cancer patients with BM in this large retrospective study. Early initiation and longer duration of denosumab treatment may generate better clinical outcomes for bone lesions by MDA criteria.

Identifying the Morphological and Molecular Features of a Cell-Based Orthotopic Pancreatic Cancer Mouse Model during Growth over Time.

Pancreatic ductal adenocarcinoma (PDAC), characterized by hypovascularity, hypoxia, and desmoplastic stroma is one of the deadliest malignancies in humans, with a 5-year survival rate of only 7%. The anatomical location of the pancreas and lack of symptoms in patients with early onset of disease accounts for late diagnosis. Consequently, 85% of patients present with non-resectable, locally advanced, or advanced metastatic disease at diagnosis and rely on alternative therapies such as chemotherapy, immunotherapy, and others. The response to these therapies highly depends on the stage of disease at the start of therapy. It is, therefore, vital to consider the stages of PDAC models in preclinical studies when testing new therapeutics and treatment modalities. We report a standardized induction of cell-based orthotopic pancreatic cancer models in mice and the identification of vital features of their progression by ultrasound imaging and histological analysis of the level of pancreatic stellate cells, mature fibroblasts, and collagen. The results highlight that early-stage primary tumors are secluded in the pancreas and advance towards infiltrating the omentum at week 5-7 post implantation of the BxPC-3 and Panc-1 models investigated. Late stages show extensive growth, the infiltration of the omentum and/or stomach wall, metastases, augmented fibroblasts, and collagen levels. The findings can serve as suggestions for defining growth parameter-based stages of orthotopic pancreatic cancer models for the preclinical testing of drug efficacy in the future.