Combination Of Systemic Therapy Research Articles

Impact on survival benefits of asymptomatic primary tumor resection after bevacizumab plus FOLFIRI as first-line therapy for patients with metastatic colorectal cancer with synchronous unresectable metastasis

BackgroundMetastatic colorectal cancer (mCRC) poses a clinical challenge and requires a combination of systemic therapy and conversion surgery. Although first-line chemotherapy and targeted therapy are considered the standard treatments for mCRC, the role of primary tumor resection (PTR) in asymptomatic synchronous mCRC with unresectable metastatic lesion after initial therapy remains relatively underexplored.MaterialsA retrospective review was conducted from January 2015 to January 2021, involving 74 patients with synchronous mCRC who received bevacizumab plus FOFIRI as first-line systemic therapy. All 74 patients had unresectable metastatic lesions confirmed through multidisciplinary team discussion. Patient characteristics, PTR data, and radiotherapy (RT) and overall survival (OS) outcomes were analyzed. The patients were categorized into a “PTR” group and a “No PTR” group and then further stratified into “4A,” “4B,” and “4C” subgroups based on the initial mCRC stage. Additionally, four subgroups—namely “PTR( +)/RT( +),” “PTR( +)/RT( −),” “PTR( −)/RT( +),” and “PTR( −)/RT( −)”—were formed to assess the combined effects of PTR and RT.ResultsThe median OS for all the patients was 23.8 months (20.5–27.1 months). The “PTR” group exhibited a significantly higher median OS of 25.9 months (21.3–30.5 months) compared with 21.4 months (15.8–27.1 months) in the “No PTR” group (p = 0.048). Subgroup analyses revealed a trend of improved survival with PTR in patients with stage IVA and IVB; however, the results were not statistically significant (p = 0.116 and 0.493, respectively). A subgroup analysis of PTR and RT combinations revealed no significant difference in median OS rates.ConclusionFor asymptomatic mCRC with synchronous unresectable distant metastasis, PTR following first-line therapy with bevacizumab plus FOLFIRI may provide a potential survival benefit, particularly in stage IVA/IVB patients compared with stage IVC patients. Additionally, RT for primary tumor did not provide an additional OS benefit in mCRC with unresectable metastasis. A prospective randomized trial with a larger sample size is essential to further elucidate the role of PTR in this context.

Durvalumab-Induced Immune Thrombocytopenia in Patients with Advanced Cholangiocarcinoma Undergoing Yttrium-90 Radioembolization

Introduction: Immune thrombocytopenia (ITP) secondary to durvalumab, a programmed cell death ligand 1 inhibitor, is a rare but clinically significant immune-related adverse event. Herein, we present 2 patients with cholangiocarcinoma who developed ITP immediately post-yttrium-90 radioembolization (Y90-RE) while on durvalumab-based systemic therapy. We hypothesize that given the timing, the immunotherapy and the radioembolization combination led to this event. It is not uncommon given the approval of immunotherapy and its role in locoregional therapies, that patients are treated with a combination of systemic immunotherapy and radioembolization or other forms of radiation, thus signifying the importance of potential complications. Case Presentation: Two patients, a 67-year-old female and a 60-year-old man, with biopsy-proven advanced unresectable cholangiocarcinoma, received a combination of systemic therapy with durvalumab, gemcitabine, and cisplatin and subsequently Y90-RE. Both patients developed ITP following in the immediate post-Y90-RE period. All other causes of ITP were comprehensively ruled out and treatment for ITP was initiated in the form of high-dose steroid and intravenous immunoglobulins. Durvalumab was discontinued, and only gemcitabine/cisplatin-based chemotherapy was continued thereafter. Due to recurrence, one of the patients required longer courses of steroids as well as thrombopoietin receptor agonists. Conclusion: Immunotherapy in the form of durvalumab and now pembrolizumab alongside chemotherapy is an approved first-line standard of care. Furthermore, it is not uncommon for patients to receive Y90-RE to improve patient outcomes. This report highlights the development of ITP in 2 patients who received durvalumab alongside Y90-RE. Awareness of this as a potential immune-mediated event is important to allow for close monitoring of platelet counts and for early intervention/management when this occurs.

Clinical study on conversion therapy of hepatocellular carcinoma - summary and comparison of clinical data from a single center of consecutive four years

AimThe purpose of this study was to interpret real-world clinical data to analyze the surgical safety and survival outcomes of patients with initial unresectable hepatocellular carcinoma (uHCC) after conversion therapy.MethodsA retrospective analysis was performed on 2984 hepatocellular carcinoma (HCC) patients hospitalized in Shandong Cancer Hospital Affiliated to Shandong First Medical University from June 1st, 2019 to June 1st, 2023. Clinicopathological features, response to systemic and/or loco-regional treatments, surgical resection rate after conversion therapy, surgical safety, and postoperative recurrence were analyzed.ResultsA total of 38 patients were successfully converted to obtain surgical resection. 35 patients underwent radical resection. A high objective response rate (ORR) (52.6% under RECIST v1.1 and 78.9% under mRECIST criteria) was observed in patients under conversion therapy, and the disease control rate (DCR) was 100%. Pathologic complete response (pCR) was 42.9%. Treatment-related adverse events (TRAEs) of any grade were observed in 37 patients (97.4%). Safety of conversion or direct surgery continues to improve. The median follow-up time was 19.3 months. The 1-year Disease-free survival (DFS) rate of patients with direct surgery and patients with conversion surgery were 91.4% and 86.8%, respectively.ConclusionsWith conversion therapy, a small percentage (1.81%) of uHCC patients are likely to be converted to radical resection. Local combined systemic therapy is a relatively safe and effective conversion therapy, and the safety of surgery is gradually improved after successful conversion. Preliminary follow-up data showed satisfactory survival benefits for patients undergoing conversion surgery.Trial registrationThis was a retrospective study and it did not interfere with treatment decisions.

Proton Therapy in Uveal Melanoma

Background/Objectives: Uveal melanoma is the most common primary intraocular malignancy in adults. Treatment options for localized, early-stage disease include enucleation, brachytherapy, and proton beam therapy. This review aims to evaluate the role of proton therapy in the definitive management of uveal melanoma, focusing on its physics, radiobiology, treatment techniques, and associated outcomes. Methods: This narrative review synthesizes current literature on proton therapy for uveal melanoma, emphasizing case selection, treatment efficacy, and side effects. Results: Proton therapy offers significant advantages for thicker uveal melanomas (over 8 mm) due to its unique physical properties, including a rapid dose fall-off that protects critical structures like the retina and optic nerve. Proton therapy may have benefits in tumor control for ocular melanomas given its increased relative biological effectiveness relative to photon therapy for these typically more radioresistant melanomas. Proton therapy may also hold special value for uveal melanomas in close proximity to the optic nerve, as patients are at high risk of visual toxicities with brachytherapy. The review discusses the efficacy of proton therapy across small, medium, and large tumors, along with strategies for improving patient survival through combined systemic therapy. Additionally, the potential of ocular reirradiation with proton therapy is addressed. Conclusions: Proton therapy is an effective treatment for uveal melanoma. It offers advantages over brachytherapy for large tumors, tumors that are close to the optic nerve or insertion of extra-ocular muscles.

286. TREATMENT WITH CURATIVE INTENT FOR OLIGOMETASTATIC GASTROESOPHAGEAL CANCER-RESULTS OF A PROSPECTIVE MULTICENTER STUDY

Abstract Background Oligometastatic gastroesophageal cancer is a clinical entity with no standard treatment recommendation. Treatment with curative intent has recently emerged as an option in selected patients in contrast to the traditional palliative treatment strategy. This prospective study aimed to assess the safety and efficacy of combined systemic and local treatment with curative intent for patients with oligometastatic gastroesophageal cancer. Methods In a multicenter collaborative study, consecutive patients with gastroesophageal cancer and metastases in the liver and/or extra-regional lymph nodes were screened for inclusion. Eligible patients were offered treatment with combined systemic and local therapy within the study. Primary endpoints were treatment safety and feasibility, secondary outcomes included postoperative mortality, treatment response, progression-free and overall survival. Subgroup analyses were stratified based on oligometastatic location. Results A total of 29/35 patients completed systemic and local treatment with surgical resection, liver ablation or definitive chemoradiotherapy. The majority of postoperative complications were mild-moderate, no patient died due to postoperative complications within 30 days of surgery. Median progression-free survival was 7.1 (interquartile range 4.3-12.4) months and median overall survival was 23.8 (interquartile range 12.3-33.0) months. Conclusion This study found combined systemic and local treatment to be a safe treatment option and to potentially improve long-term survival in strictly selected patients with oligometastatic gastroesophageal cancer.

Clinical characteristics, management, and survival of retinoblastoma patients: a five-year study at an Indonesian tertiary eye hospital

Background Studies on the clinical characteristics of retinoblastoma in Indonesia have been limited, even though retinoblastoma is the most common pediatric ocular malignancy worldwide and the second-most common pediatric malignancy in Indonesia. The estimated patient survival rate in lower-middle-income countries is 77%, and survival is highly dependent on early diagnosis and therapy. Objective To identify the clinical characteristics of retinoblastoma in patients at the Cicendo National Eye Hospital, as an Indonesian tertiary eye hospital. Methods This retrospective, observational study included pediatric patients <18 years of age diagnosed with retinoblastoma at the Cicendo National Eye Hospital, Bandung, West Java, between January 2018 and December 2022. We collected patients’ medical record data on age, gender, laterality, chief complaints, stage of disease, grouping, histopathologic features, therapy, and survival. Results Of 247 retinoblastoma patients (328 eyes) enrolled, 53.85% presented at 1-2 years of age and 50.61% were males. Patients mostly presented with unilateral (67.21%) retinoblastoma, leukocoria (51.82%) as the chief complaint, and classified as International Retinoblastoma Staging System (IRSS) stage III (33.20%). Tumors were mostly intraocular (58.84%), particularly group E (39.02%). Most tumors showed undifferentiated (45.43%) and high-risk features (54.27%). Most eyes were treated with combination therapy (74.09%), particularly local and systemic therapy (59.45%). Survival was noted at 18.62% of patients, but 62.75% of patients were lost to follow-up. Conclusion Most patients present with advanced retinoblastoma. Most histopathological results shows undifferentiated and high-risk features of the tumor. Delays in diagnosis and therapy may occur due to a lack of awareness and knowledge regarding clinical manifestations of retinoblastoma, which leads to worse prognosis.

Combination Therapy Consisting of Transarterial Chemoembolization, Lenvatinib, and Programmed Cell Death Protein 1 Blockade for Hepatocellular Carcinoma with Inferior Vena Cava Tumor Thrombus: A Case Series Study and Literature Review

Introduction: Patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor thrombus (IVCTT) have poor prognosis. Combination therapy involving the blockade of programmed cell death protein 1 (PD-1) and tyrosine kinase inhibitors is an efficient treatment strategy for advanced HCC. However, surgical treatment after a combination of systemic therapy and transarterial chemoembolization (TACE) for HCC with IVCTT has not been widely reported, and the efficacy and safety of this treatment have not been studied. Methods: In the 21 cases reported herein, the patients were treated with TACE, lenvatinib, and PD-1 blockade. The treatment responses, progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities were evaluated, and the related literature was reviewed. Results: The overall response and disease control rates were 66.7% and 85.7%, respectively. The median PFS time was 16.0 months, with a 1-year PFS rate of 55.60%. The median OS was not reached, with a 1-year OS rate of 66.70%. Four patients underwent hepatectomy without serious complications and survived for 29.1, 24.7, 14.2, and 13.8 months. Three patients survived tumor-free, and 1 patient experienced intrahepatic recurrence. Pathological complete response and major pathological responses were observed in 1 and 3 patients, respectively. Treatment-related adverse events of any grade occurred in 8/9 patients (88.9%), and grade 3 treatment-related adverse events occurred in 1 patient. Conclusion: The combination of TACE, lenvatinib, and PD-1 is effective for HCC with IVCTT and has acceptable adverse effects.

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.

Liver Transplantation for Cholangiocarcinoma

AbstractCholangiocarcinomas (CCAs) are highly aggressive, primary liver cancers with rising incidence and mortality rates. The current 5-year overall survival is less than 20%. There are no standardized screening protocols, and current diagnostic methods include serum biomarkers and imaging techniques with suboptimal sensitivities and specificities. The most commonly used treatment options, including combination systemic therapies, locoregional therapies, and surgical resection, offer improving but nonetheless limited progression-free and overall survival. Liver transplantation has shown promising results as a potentially curative treatment for two types of CCA, namely, perihilar and intrahepatic. However, the evidence is largely from retrospective series of small to moderate sample sizes. There is a need to define optimal types and sequencing of neoadjuvant and adjuvant peritransplant therapies, as well as criteria for CCA patient transplant eligibility. Here, we conduct a granular review of the evidence available on every step of the transplant care pathway for perihilar and intrahepatic CCA patients. We aim to inform best practices to inform future avenues of research and maximize the number of patients eligible for this potentially life-prolonging therapy.

Site-Specific Response and Resistance Patterns in Patients with Advanced Non-Small-Cell Lung Cancer Treated with First-Line Systemic Therapy.

Patients with advanced NSCLC have heterogenous responses to immune checkpoint inhibitors (ICIs) with or without chemotherapy. In NSCLC, the impact of the distribution of metastatic sites and the response to systemic therapy combinations remain poorly understood. In a retrospective cohort study of patients with unresectable stage III/IV NSCLC who received first-line systemic therapy, we sought to assess the association between the site of metastases with patterns of response and progression. Data regarding demographics, tumour characteristics (including site, size, and volume of metastases), treatment, and outcomes were examined at two cancer care centres. The endpoints included organ site-specific response rate, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Two-hundred and eighty-five patients were included in the analysis. In a multivariate analysis, patients with bone metastases had a reduced ORR, PFS, and OS. Primary resistance was also more likely in patients with bone metastases. Patients with bone or liver metastases had a shorter OS when receiving ICIs with or without chemotherapy, but not with chemotherapy alone, suggesting an immunological basis for therapeutic resistance. A directed assessment of the tumour microenvironment in these locations and a deeper understanding of the drivers of organ-specific resistance to immunotherapy are critical to optimise novel combination therapies and sequencing in these patients.

Retrospective evaluation of the effectiveness and safety of UVB-311 in atopic dermatitis

BACKGROUND: Atopic dermatitis is a widespread skin disease based on immune and genetic mechanisms of chronic inflammation formation. The disease most often develops in early childhood, has a frequent recurrent course, age-related clinical features. In this regard, the disease is characterized by a wide variety of treatment methods, the effectiveness of which varies and is a highly debated topic at the present time. AIM: to retrospectively evaluate the efficacy and safety of standard local and systemic therapy of atopic dermatitis in combination with UVB 311 nm. MATERIALS AND METHODS: 100 case histories of patients with atopic dermatitis of varying severity who were in the clinic of skin and venereal diseases in the period from 2022 to 2023 were analyzed. Of these, 50 patients received combined systemic and topical therapy with UVB 311 nm (the first group), and 50 patients received only standard topical and systemic therapy (the second group). Systemic and topical therapy of atopic dermatitis included, according to clinical recommendations, corticosteroids, calcineurin inhibitors, antihistamines. RESULTS: As a result of combined therapy with UVB 311 nm, patients showed a decrease in the SCORAD index by 1.7 times after 1 month of therapy, by 8 times after 2 months, and by 30 times after 6 months. In the second group, the SCORAD index decreased 1.2 times after 1 month from the start of therapy (p=0.0004), 3 times after 2 months (p=0.0001), 20 times after 6 months (p=0.003). Side effects in the first group were detected only in 5 (10%) patients: 2 (4%) patients had skin burning, 2 (4%) had skin itching, 1 (2%) patient had photodermatitis in the form of erythema of the skin. These adverse reactions were of a short-term nature and quickly passed if the recommendations were followed without canceling the procedures. CONCLUSION: UVB 311 nm therapy for atopic dermatitis has a higher therapeutic effect, is well tolerated, has minimal early side effects, and leads to clinical remission faster than standard systemic and local therapy.

Abstract PO1-05-14: Outcomes of first-line chemotherapy for visceral crisis in metastatic breast cancer

Abstract Background: Visceral crisis (VC) in metastatic breast cancer (BC) is defined as severe organ dysfunction, as assessed by signs and symptoms, laboratory tests, and rapid disease progression. The management of this condition is currently based on limited retrospective evidence and expert opinions, since VC has been a common exclusion criterion in clinical trials. There is a paucity of real-world data regarding the management of BC VC. We aim to evaluate the survival outcomes and prognostic factors of first-line palliative chemotherapy for VC in a tertiary cancer center in Brazil. Methods: Data were retrospectively collected from patients with metastatic BC diagnosed with VC between 2017 and 2022 in a single cancer center. Our analysis focused on patients receiving first-line chemotherapy for VC. Patients with hormone receptor-positive BC could have been previously treated with endocrine therapy for metastatic disease. CDK4/6 inhibitors were not available in the cancer center during the study period. Prognostic factors associated with survival were evaluated through univariate and multivariable analyses, using the Cox regression model. Results: A total of 106 patients with VC were evaluated. Among them, 58.5% (62 patients) had not received any previous line of chemotherapy in the metastatic setting before the diagnosis of VC (1st line cohort). Median overall survival (mOS) in the total population was 1.7 months, significantly distinct from the 1st line cohort, which had a mOS of 4.9 months (p < 0.001). Focusing on the 1st line cohort, the most common type of VC was pulmonary (40.3%), followed by hepatic (24.2%), and medullary infiltration (21%). 66.1% of patients had HR+HER2- (mOS 9.3 months), 19.3% HER2+ (mOS 4.5 months), and 11.3% triple-negative BC (TNBC) (mOS 1.5 months). Most patients were treated for VC based on systemic therapy combinations (59.7%), while 32.2% received monochemotherapy, and 8.1% were managed with best supportive care (BSC) alone. In the population receiving multidrug therapy, the mOS was 9.3 months, compared to 4.9 months with monochemotherapy and 0.7 months in patients undergoing BSC. Nevertheless, the type of treatment received was not associated with OS in the multivariable analysis. In the multivariable analysis, the prognostic factors associated with worse mOS were TNBC subtype, hepatic VC), and ECOG-PS > 2. (Table). Among patients with hepatic VC, 73.7% died during the same hospitalization and 60.5% received chemotherapy within 30 days prior to death. Conclusions: Patients with VC due to BC have a poor prognosis, even in the context of first-line chemotherapy. Factors such as ECOG-PS, BC subtype, and VC type should be taken into account when discussing the expected outcomes of this life-threatening condition. Taking these factors into account can help physicians to differentiate patients who are more likely to benefit from systemic oncologic treatment from those for whom such therapy would be futile or potentially harmful. Median overall survival according to baseline characteristics and multivariable analysis (1st line cohort, n=62) Citation Format: Matheus de Oliveira Andrade, Vitor Hugo Felix, Renata Colombo Bonadio, Laura Testa. Outcomes of first-line chemotherapy for visceral crisis in metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-05-14.

Clinico–pathologic factors and survival of patients with breast cancer diagnosed with de novo brain metastasis: a national cancer database analysis

PurposePatients with Breast Cancer (BC) with Brain Metastasis (BCBM) have poor survival outcomes. We aimed to explore the clinico–pathologic and therapeutic factors predicting the survival in patients with de novo BCBM using the National Cancer Database (NCDB).Patients and methodsThe NCDB was queried for patients with BC between 2010 and 2020. Survival analysis with Kaplan–Meier curves and log rank tests were used to find median overall survival (OS) in months (95% CI) across the different variables. A multivariate cox regression model was computed to identify significant predictors of survival.ResultsOut of n = 2,610,598 patients, n = 9005 (0.34%) had de novo BCBM. A trend of decreasing OS was observed with increasing age, Charlson–Deyo score (CDS), and number of extracranial metastatic sites. The highest median OS was observed in the Triple Positive and the lowest OS in the Triple Negative subgroup. Based on treatment regimen, combination of systemic therapy and local therapy achieved the highest OS. A positive trend in OS was observed in the BC subgroup analysis with targeted therapy demonstrating a survival benefit when added to systemic therapy.The multivariate cox regression model showed that age, race, ethnicity, insurance, median income, facility type, CDS, BC subtype, metastatic location sites, and treatment combinations received were significantly associated with risk of death. Receiving only local treatment for BM without systemic therapy more than doubled the risk of death compared to combining it with systemic therapy.ConclusionsThis analysis suggests that treatment of systemic disease is the major factor influencing survival in patients with BCBM. Moreover, targeted therapy with anti–HER2 increased survival when added to systemic therapy explaining the highest median OS noted in the Triple Positive subgroup.

Fractionated stereotactic radiotherapy of intracranial postoperative cavities after resection of brain metastases – Clinical outcome and prognostic factors

Background and PurposeAfter surgical resection of brain metastases (BM), radiotherapy (RT) is indicated. Postoperative stereotactic radiosurgery (SRS) reduces the risk of local progression and neurocognitive decline compared to whole brain radiotherapy (WBRT). Aside from the optimal dose and fractionation, little is known about the combination of systemic therapy and postoperative fractionated stereotactic radiotherapy (fSRT), especially regarding tumour control and toxicity. MethodsIn this study, 105 patients receiving postoperative fSRT with 35 Gy in 7 fractions performed with Cyberknife were retrospectively reviewed. Overall survival (OS), local control (LC) and total intracranial brain control (TIBC) were analysed via Kaplan-Meier method. Cox proportional hazards models were used to identify prognostic factors. ResultsMedian follow-up was 20.8 months. One-year TIBC was 61.6% and one-year LC was 98.6%. Median OS was 28.7 (95%-CI: 16.9–40.5) months. In total, local progression (median time not reached) occurred in 2.0% and in 20.4% radiation-induced contrast enhancements (RICE) of the cavity (after median of 14.3 months) were diagnosed. Absence of extracranial metastases was identified as an independent prognostic factor for superior OS (p = <0.001) in multivariate analyses, while a higher Karnofsky performance score (KPS) was predictive for longer OS in univariate analysis (p = 0.041). Leptomeningeal disease (LMD) developed in 13% of patients. ConclusionFSRT after surgical resection of BM is an effective and safe treatment approach with excellent local control and acceptable toxicity. Further prospective randomized trials are needed to establish standardized therapeutic guidelines.

Neoadjuvant chemo-immunotherapy is improved with a novel pulsed electric field technology in an immune-cold murine model.

Chemo-immunotherapy uses combined systemic therapies for resectable and unresectable tumors. This approach is gaining clinical momentum, but survival increases leave considerable room for improvement. A novel form of Pulsed Electric Field (PEF) ablation combines focal tissue destruction with immune activation in preclinical settings. The PEFs induce lethal cell damage without requiring thermal processes, leaving cellular proteins intact. This affords PEF a favorable safety profile, improved antigenicity, and significant immunostimulatory damage-associated molecular pattern release compared to other focal therapies. Preclinical investigations demonstrate a combinatorial benefit of PEF with immunostimulation. This study evaluates whether this proprietary PEF therapy induces an immunostimulatory effect sufficient to augment systemic neoadjuvant chemotherapy and immunotherapy to reverse metastatic disease in an immune-cold murine tumor model. To determine whether PEF improves a neoadjuvant chemo-immunotherapy standard-of-care, partial PEF ablation was delivered to orthotopically inoculated 4T1 metastatic tumors in addition to combinations of cisplatin chemotherapy and/or αPD-1 immunotherapy, followed by resection. In addition, to determine whether PEF combined with chemo-immunotherapy improves local and metastatic response in unresectable populations, partial PEF ablation was added to chemo-immunotherapy in mice that did not receive resection. Blood cytokines and flow cytometry evaluated immune response. Partial PEF ablation generates an immunostimulatory tumor microenvironment, increases systemic immune cell populations, slows tumor growth, and prolongs survival relative to neoadjuvant systemic therapies-alone. These data suggest the addition of this proprietary PEF locoregional therapy may synergize with systemic standard-of-care paradigms to improve outcomes with potential or demonstrated metastatic disease in both resectable and unresectable patient cohorts.

Clinical characteristics, imaging features, and outcomes of primary hepatic angiosarcoma: A single‐center study and literature review

AbstractPrimary hepatic angiosarcoma (PHA) accounts for 0.5% to 2% of all primary hepatic malignancies, and histopathology findings are required to diagnose PHA accurately. This study investigated 12 patients with PHA at a single medical center in southern Taiwan. We analyzed the clinical characteristics, imaging features, histopathology findings, and survival outcomes of patients with PHA. Of the 12 patients, abdominal pain and fullness were the most common symptoms, and their liver biochemistry data and tumor markers were mostly within the normal limits. The liver tumors tended to present as multifocal or diffuse nodules with bilobar involvement. The median overall survival (OS) of the 12 patients after diagnosis was 9 months. Improved OS was observed in the surgery group compared with the nonsurgery group (15 vs. 2 months, p = .003). The median OS of patients in the surgery ± systemic therapy group was superior to that of patients in the systemic therapy group and in the no‐therapy groups (15 vs. 5 vs. 2 months, respectively; p = .012). Complete surgical resection remains the optimal treatment choice, and combined surgery and systemic therapy seem beneficial but require further investigation.

Effectiveness of combined local therapy with antibiotics and fibrin vs. vacuum-assisted wound therapy in soft tissue infections: a retrospective study.

Soft tissue infections can be severe and life-threatening. Their treatment consists currently in radical surgical wound debridement and combined systemic antimicrobial therapy. Different side effects are possible. Local antibiotic therapy represents a new approach to reduce side effects and improve healing. The aim of this study is to assess the effectiveness of the local sprayed use of antibiotics with fibrin sealing compared with negative pressure wound therapy as an established treatment of soft-tissue infections. In this retrospective study, patients with soft tissue infections who underwent surgical treatment were analysed. One group consists of patients, who received local fibrin-antibiotic spray (FAS) (n = 62). Patients treated by vacuum-assisted wound therapy (VAWT) as the established treatment were the control group (n = 57). Main outcomes were differences in the success of healing, the duration until healing and the number of needed operations. Clinical healing could be achieved for 55 patients (98.21%) in the FAS group vs. 47 patients (92.16%) in the VAWT group (p = 0.19). Time to require this was 10.65 ± 10.38days in the FAS group and 22.85 ± 14.02days in the VAWT group (p < 0.001). In the FAS group, patients underwent an average of 1.44 ± 0.72 vs.3.46 ± 1.66 operations in the VAWT group (p < 0.001). Compared to vacuum-assisted wound therapy in soft tissue infections, local fibrin-antibiotic spray shows faster clinical healing and less needed operations. Leading to shorter hospital stays and more satisfied patients. The combination of sprayed fibrin and antibiotics can be seen as a promising and effective method.

Neoadjuvant systemic therapy for hepatocellular carcinoma.

Surgical resection and liver transplant remain the only curative therapies for most patients with hepatocellular carcinoma (HCC). Systemic therapy options have typically been ineffective, but recent advances, such as the combination of immune checkpoint inhibitors and targeted therapies, have shown great promise. Neoadjuvant systemic therapy in resectable or locally advanced HCC is under active investigation with encouraging results in small, early-phase trials. Many of these completed and ongoing trials include combinations of systemic therapy (e.g. immune checkpoint inhibitors, tyrosine kinase inhibitors), transarterial therapies, and radiation. Despite early successes, larger trials with evaluation of long-term oncologic outcomes are needed to determine the role of neoadjuvant systemic therapy in patients with HCC who may be eligible for curative intent surgery or transplant.

Differences between Survival Rates and Patterns of Failure of Patients with Lung Adenocarcinoma and Squamous Cell Carcinoma Who Received Single-Fraction Stereotactic Body Radiotherapy.

We investigated the survival and patterns of failure in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) in early stage non-small cell lung cancer (NSCLC) treated with single-fraction stereotactic body radiation therapy (SF-SBRT) of 27-34 Gray. A single-institution retrospective review of patients with biopsy-proven early stage ADC or SCC undergoing definitive SF-SBRT between September 2008 and February 2023 was performed. The primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcomes included local failure (LF), nodal failure (NF), and distant failure (DF). Of 292 eligible patients 174 had adenocarcinoma and 118 had squamous cell carcinoma. There was no significant change in any outcome except distant failure. Patients with ADC were significantly more likely to experience distant failure than patients with SCC (p = 0.0081). In conclusion, while SF-SBRT produced similar LF, NF, DFS, and OS, the higher rate of distant failure in ADC patients suggests that ongoing trials of SBRT and systemic therapy combinations should report their outcomes by histology.

Recurrence risk stratification of hepatocellular carcinomas based on immune gene expression and features extracted from pathological images.

Immune-based therapy is a promising type of treatment for hepatocellular carcinoma (HCC) but has only been partially successful due to the high heterogeneity in HCC tumor. The differences in the degree of tumor cell progression and in the activity of tumor immune microenvironment could lead to varied clinical outcome. Accurate subgrouping for recurrence risk is an approach to address the issue of such heterogeneity. It remains under investigation as whether integrating quantitative whole slide image (WSI) features with the expression profile of immune marker genes can improve the risk stratification, and whether clinical outcome prediction can assist in understanding molecular biology that drives the outcome. We included a total of 231 patients from the Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) project. For each patient, we extracted 18 statistical metrics corresponding to a global region of interest and 135 features regarding nucleus shape from WSI. A risk score was developed using these image features with high-dimensional survival modeling. We also introduced into the model the expression profile of 66 representative marker genes relevant to currently available immunotherapies. We stratified all patients into higher and lower-risk subgroup based on the final risk score selected from multiple models generated, and further investigated underlying molecular mechanisms associated with the risk stratification. One WSI feature and three immune marker genes were selected into the final recurrence-free survival (RFS) prediction model following the best integrated modeling framework. The resultant score showed a significantly improved prediction performance on the test dataset (mean time-dependent AUCs = 0.707) as compared to those of other types (e.g: mean time-dependent AUCs of AJCC tumor stage = 0.525) of input data integration. To assess that the risk score could provide a higher-resolution risk stratification, a lower-risk subgroup (or a higher-risk subgroup) was arbitrarily assigned according to score falling below (or above) the median score. The lower risk subgroup had significantly longer median RFS time than that of the higher-risk patients (median RFS = 903 vs. 265 days, log-rank test p-value< 0.0001). Additionally, the higher-risk subgroup, in contrast to the lower-risk patients were characterized with a significant downregulation of immune checkpoint genes, suppressive signal in tumor immune response pathways, and depletion of CD8 T cells. These observations for the higher-risk subgroup suggest that new targets for adoptive or checkpoint-based combined systemic therapies may be useful. We developed a novel prognostic model to predict RFS for HCC patients, using one feature that can be automatically extracted from routine histopathological images, as well as the expression profiles of three immune marker genes. The methodology used in this paper demonstrates the feasibility of developing prognostic models that provide both useful risk stratification along with valuable biological insights into the underlying characteristics of the subgroups identified.