Traditional Systemic Therapies Research Articles

EFFECTIVENESS OF AUTOLOGOUS PLATELET-RICH PLASMA FOR HEALING DIABETIC FOOT ULCERS

Autologous platelet-rich plasma (APRP) is widely used to accelerate the healing of chronic wounds. However, the advisability of its use in patients with diabetic foot ulcers (DFU), which develop in various forms of the disease and are associated with complex metabolic conditions, is still being discussed. This study consisted in a comparative analysis of the effectiveness of local use of autologous platelet-rich plasma in the treatment of DFU in patients with neuropathic and neuroischemic forms of the disease. A total of 106 patients with type 2 diabetes mellitus undergoing hospital treatment were divided into a study group (n=48) and a traditional wound therapy group (n=58), similar in ankle-brachial index values ​​and ulcer size. Systemic therapy in both groups of patients included measures to regulate metabolism and nutrition, and infection control. Treatment results were assessed by the area of foot wounds and duration of healing. The duration of therapy and the mean platelet concentration in autologous plasma did not differ between groups. The wound healing time in patients with the neuropathic form (60.4±23.77 days) and the neuroischemic form of the disease (64.8±29.6 days) during treatment with APRP was significantly shorter than in the subgroups of the comparison group with traditional treatment of DFU (85.11±40.7 and 90.40±47.12 days respectively) (p<0.01), but there was no significant difference between the subgroups receiving treatment with APRP. Although there was no significant difference in the average daily healing area among all subgroups (p>0.05), the rate of wound healing in the subgroups with APRP was higher (14.85±10.66 and 15.33±14.91 mm2/day, respectively) than in the subgroups of the comparison group (8.39±6.02 and 8.79±7.13 mm2/day, respectively), which confirms the effectiveness of local treatment with APRP in combination with traditional systemic therapy.

Isolated liver chemoperfusion in a patient with mesenteric leiomyosarcoma and liver metastasis

Background. Treatment for inoperable secondary liver cancer remains challenging especially in patients with colorectal cancer. Traditional systemic drug therapy is often ineffective, and the use of transarterial chemoembolization is limited due to the systemic toxicity of some drugs. Combining high efficacy and low systemic toxicity, isolated chemoperfusion is a promising treatment option for patients with liver metastasis. Case report. A patient with mesentery leiomyosarcoma underwent several surgeries and chemotherapy courses, but liver metastases continued to grow. Isolated liver chemoperfusion with melphalan was performed after resection of liver segment and mobilization of liver vessels. To reduce the tumor volume and prevent complications, atypical liver resection was also performed. Conclusion. Isolated liver chemoperfusion for the treatment of liver cancer remains a subject of debate and is not included in the standards for treatment of primary and metastatic liver tumors. This technique was shown to be safe and promising in treating liver metastasis from leiomyosarcoma. However, further research is required to assess the role of this procedure in overall survival.

Real-world evaluation of clinical outcomes and long-term survivors in patients with BRAF-V600E metastatic colorectal cancer.

166 Background: BRAF-V600E mutant metastatic colorectal cancer (BRAF-V600E mCRC) is associated with poor prognosis but confers response to combination BRAF/EGFR blockade. The goal of this study is to evaluate the clinicopathologic features and natural history of BRAF-V600E mCRC in the era prior to combination BRAF/EGFR inhibitors. Methods: This is a retrospective study of patients treated at the Ottawa Hospital Cancer Centre with BRAF-V600E mCRC who did not receive combination BRAF/EGFR therapy. Patients diagnosed with colorectal cancer prior to March 31, 2021, were included. Demographic, clinical, pathologic and cancer characteristics were abstracted from electronic medical records. Outcomes of interest included duration of therapy, as a surrogate of progression free survival, and overall survival (OS). Long-term survivor was defined as OS greater than 2 years. Results: 74 patients were included. Median age was 70 years (IQR=61-78), and 39 (53%) patients were female. There were 17 (23%) patients alive at the end of the follow-up period. 31 (42%) patients had poorly differentiated grade and 26 (35%) were mismatch repair deficient (dMMR). Locations of metastases included liver (40, 54%), peritoneum (30, 41%), lung (18, 24%), bone (5, 7%) and brain (5, 7%). Overall, 64 (86%) patients received first line systemic therapy, 19 (26%) second line, and 5 (7%) third line (see Table). Median duration of therapy in the first line was 4.3 months (IQR=2.0-9.6), second line was 2.9 months (IQR=1.4-4.1), and third line 1.0 months (IQR=1.0-1.9). Overall survival in the entire cohort was 13.2 months (IQR=4.6-25.4). Importantly, 21 (28%) patients were long-term survivors, of which 8 (11%) were dMMR. Conclusions: Patients with BRAF-V600E mCRC generally have poor clinical outcomes with traditional systemic therapies. In this study, we identified approximately 25% of patients who are long-term survivors (OS >2 years). This reflects the real-world heterogeneity of clinical outcomes for patients with BRAF-V600E mCRC who did not receive BRAF/EGFR targeted therapy.[Table: see text]

Biologics as a novel treatment option for palmoplantar pustulosis: a comprehensive review.

Palmoplantar pustulosis (PPP) is a complex inflammatory skin disease. Currently, no standardized treatments exist, and traditional systemic therapies often display limited effectiveness and substantial adverse effects. Biologics, however, have shown potential for enhanced clinical outcomes in psoriasis patients, thereby prompting this investigation into their applicability in PPP treatment. This study constitutes the first comprehensive review to assess the effectiveness and underlying mechanisms of biologics for PPP. We conducted a PubMed search to identify studies on biologics for PPP from 1992 onward. The review focused on assessing the efficacy of biologics targeting cytokines like IL-1, IL-8, IL-17, IL-12/23, IL-36, and TNF-α. Biologics for PPP are generally less effective than for psoriasis. Secukinumab and guselkumab, IL-17 and IL-23 inhibitors respectively, have shown better results compared to other biologics in trials. However, the effectiveness of other biologics remains uncertain due to limited data. More research is needed to find effective treatments for PPP, and selecting the right biologic for each patient is challenging.

The Impact of Social Determinants of Health on Brexucabtagene Autoleucel Outcomes in Adults with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia

Background Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR-T) cell therapy that recently received U.S. FDA approval as the first CAR-T cell therapy for adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). Social determinants of health (SDoH) are shown to significantly influence outcomes in B-ALL. However, how SDoH relate to and affect outcomes in patients with B-ALL receiving CAR-T therapy has not been well established. We studied the impact of SDoH on outcomes of adults with B-ALL receiving brexu-cel as part of the Real-world Outcomes Collaborative of CAR-T in Adult ALL (ROCCA). Methods This retrospective multicenter analysis spanning 25 U.S centers included adults (≥18 years) with r/r B-ALL treated with commercial brexu-cel between 2021-2023. Progression-free survival (PFS) and overall survival (OS) were calculated from the day of brexu-cel infusion and were not censored for hematopoietic cell transplant (HCT) or maintenance. Univariate and multivariate Cox proportional hazards models were used to evaluate the association of age, sex, pre-apheresis disease burden, and SDoH (referral source, insurance, distance from home to CAR-T site, marital status, and the social deprivation index) with progression-free survival (PFS) and overall survival (OS). The social deprivation index (SDI), a composite measure (including income, education, employment, housing, household characteristics, and transportation) used to quantify socio-economic variation in health outcomes, with higher SDI indicating greater social disadvantage, was estimated at the zip code level. (Butler et al., 2013) Results Of the 152 patients who received brexu-cel (Table 1), 57% were male. 51% identified as non-Hispanic White, with the remainder identifying as Hispanic (34%), Asian/Pacific Islander (7%), Black (6%), American Indian/Alaskan Native (1%), or mixed race (1%). A majority (46%) were referred for brexu-cel from private/community-based practices and 62% lived within 50 miles of the CAR-T center (36% lived >50 miles and 2% were unknown). Health insurance coverage included primarily public (49%) and private (42%); no patients were uninsured. High SDI (76-100% percentile) was present in 26%, while 14% had a low SDI (0-25 th percentile). In unadjusted analyses, there was no difference in PFS or OS between patients with high versus low SDI; closer distance to the CAR-T site (<50 miles versus >50 miles)) was associated with worse OS (HR 1.96; 95% CI 1.00, 3.84; p=0.05). Multivariate analysis (Table 2) revealed that male sex was associated with inferior PFS (HR 1.98; 95% CI 1.02, 3.85; p=0.04) and OS (HR 2.52; 95% CI 1.09, 5.84; p=0.03). There was no difference in PFS (HR 0.95, 95% CI 0.48-1.88, p=0.88) or OS (HR 0.80; 95% CI 0.33,1.92; p=0.62) when comparing Hispanic and non-Hispanic White patients. Additionally, there was no difference in PFS or OS based on any SDoH, including insurance type, marital status, referral source, caregiver type, and distance to transplant center. Conclusions In patients receiving brexu-cel, survival outcomes appear independent of SDoH. Contrary to previous reports suggesting inferior outcomes for Hispanic patients with B-ALL after receiving traditional systemic therapies, we observed comparable outcomes to non-Hispanic patients treated with brexu-cel. Distance from the CAR-T site and referrals from the community did not affect outcomes. Additionally, those with higher SDI had similar outcomes to those with a lower SDI, although this analysis was limited by sample size and the selection bias that exists in being referred for brexu-cel in the first place. The relatively lower logistical burden of CAR-T compared to allogeneic stem cell transplant or non-fixed duration systemic therapies may have mitigated the impact of SDoH on outcomes. These real-world data suggest that continuing to improve access to and treatment with brexu-cel may improve overall outcomes for disadvantaged populations with r/r B-ALL.

Corrigendum: treatments for resectable esophageal cancer: from traditional systemic therapy to immunotherapy.

Corrigendum: treatments for resectable esophageal cancer: from traditional systemic therapy to immunotherapy.

Management Strategies for Pediatric Moderate-to-Severe Plaque Psoriasis: Spotlight on Biologics.

Although psoriasis onset has been reported at any ages, in up to one-third of cases, it begins during childhood, with an estimated prevalence of about 2% in pediatric population. The management of moderate-to-severe forms of childhood psoriasis may represent a challenge for dermatologists, especially for parents' concerns about the need of systemic treatments. However, a prompt safe and effective treatment is mandatory in these patients, due to the significative impact that psoriasis may have on their quality of life, with well-known consequences on psychological health of both patients and caregivers. Due to the relatively frequent parents' refusal of systemic treatments, probably due to the fear of eventual adverse events, difficulties of oral or injective route, the management of moderate-to-severe forms still represents a challenge. Herein, we report a narrative review, aiming to resume the systemic treatments for pediatric psoriasis, focusing on the use of biologics and small molecules in the pediatric ages. The most widely used therapeutic strategies today for the pediatric population with moderate-severe psoriasis are traditional systemic therapies, while more innovative drugs such as biologics and small molecules now represent a somewhat unexplored but certainly promising field for unresponsive patients.

Treatment of Recurrent Low-grade Serous Ovarian Cancer With MEK Inhibitors: A Systematic Review.

Low-grade serous ovarian cancer (LGSC) represents 5% of all epithelial ovarian cancers. They are characterized by indolent growth and KRAS and BRAF mutations, differing from high-grade serous ovarian cancer both clinically and molecularly. LGSC has low response rates to traditional systemic therapies, including chemotherapy and hormonal therapy. The objective of this systematic review was to appraise the literature describing the efficacy of MEK inhibitors in the treatment of LGSC. A comprehensive search was conducted of the following databases: Medline ALL, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Sciences, ClinicalTrials.gov, International Clinical Trials Registry Platform (ICFRP), and International Standard Randomized Controlled Trials Number (ISRCTN) Registry. All studies investigating MEKi in the treatment of LGSC in the adjuvant or recurrent setting for patients 18 years of age or older were included. All titles/abstracts were then screened by 2 independent reviewers (A.K. and C.C.). The full-text articles were then screened. All disagreements were resolved by a third independent reviewer (T.Z.). Two independent reviewers (A.K. and C.C.) extracted data from the studies deemed eligible for final review. A total of 2108 studies were identified in the initial search. Of these, a total of 4 studies met the eligibility criteria for systematic review. In these studies, 416 patients were treated with an MEKi alone. All patients included in the studies were being treated for LGSC in the recurrent setting. Varied results and efficacy of the MEKi were reported in each study. The results highlighted in this systematic review demonstrate varied responses to MEKi for recurrent LGSC. Further research is needed in this field comparing the efficacy to current therapies, as well as to further evaluate the safety and toxicity profile with long-term use of MEKi.

43852 JAK inhibitor safety compared to traditional systemic immunosuppressive therapies

43852 JAK inhibitor safety compared to traditional systemic immunosuppressive therapies

Oncolytic Virotherapy for High-Grade Glioma and Current Evidence and Factors to Consider for Incorporation into Clinical Practice.

Brain tumor incidence is on the rise, and glioblastoma comprises the majority of primary tumors. Despite maximal safe resection and adjuvant chemoradiation, median survival for high-grade glioma remains poor. For this reason, it is important to develop and incorporate new treatment strategies. Oncolytic virotherapy has emerged as a viable new therapeutic entity to fill this gap. Preclinical research has shown oncolytic virotherapy to be a robust and effective treatment option for brain tumors, and clinical trials for both adult and pediatric high-grade glioma are underway. The unique and protected environment of the nervous system, in part due to the blood-brain barrier, prevents traditional systemic therapies from achieving adequate penetration. Brain tumors are also heterogenous in nature due to their diverse molecular profiles, further complicating systemic treatment efforts. Oncolytic viruses may serve to fill this gap in brain tumor treatment given their amenability to genetic modification and ability to target unique tumor epitopes. In addition, direct inoculation of the oncolytic virus agent to the tumor bed following surgical resection absolves risk of systemic side effects and ensures adequate delivery. As virotherapy transitions from bench to bedside, it is important to discuss factors to make this transition more seamless. In this article, we describe the current clinical evidence as it pertains to oncolytic virotherapy and the treatment of brain tumors as well as factors to consider for its incorporation into neurosurgical workflow.

422 Healthcare disparities in atopic dermatitis: insights from TARGET-DERM registry

Abstract Atopic dermatitis disproportionately affects diverse patient populations. Furthermore, complex factors may influence the burden of disease and access to treatment amongst different racial and ethnic groups. The aim of this study is to evaluate health disparities and real-world management patterns in distinct populations treated for AD in routine clinical practice. The study included patients with AD (≥age 6) enrolled in TARGET-DERM, an observational, longitudinal study of over 2500 participants across 43 US academic/community centers. Participants were classified in four race/ethnicity categories as reported in enrollment forms and/or patient self-reported: non-Hispanic (NH) White, Black, Asian/Pacific Islander (API) and Hispanic. Patient characteristics analysed included demographics, clinical characteristics, investigator-assessed and patient-reported outcomes, and treatment history. A total of 1928 patients (mean age 34 years; 58% female; 60% enrolled at community-based centers) were included, encompassing 251 NH-Black (13%), 271 NH-API (14%), 288 Hispanic (15%) and 1118 NH-White (58%) participants. Most (71%) had a medical comorbid condition with 30% having ≥3 conditions. Private insurance was highest among NH-APIs (82%) and NH-Whites (70%), Medicaid was highest among Hispanics (46%) and NH-Blacks (27%), and uninsured was highest among NH-Blacks (18%) and NH-Whites (12%). At enrollment, clinical disease severity assessments [vIGA-AD, TBSA and vIGA-ADxTBSA (VxT)] varied by race/ethnicity, also suggesting healthcare disparities. Lowest severity was among NH-Whites (25.9% vIGA-AD clear/almost clear, 26.7% VxT clear/almost clear and median TBSA 5%), followed by Hispanics (21.7%, 18.2% and 7%), NH-Blacks (15.7%, 15.3% and 10%), and NH-APIs (10.7%, 13.8% and 8%). No differences were identified in the distribution of traditional systemic therapies across groups. However, in multivariable analysis (adjusted for age, sex, insurance status, comorbidities, vIGA and treatment status), NH-Blacks and Hispanics were less likely to be treated with advanced systemic therapies than NH-Whites [odds ratio (OR) of 0.67 and 0.70, respectively; P < 0.01]. Similarly, NH-APIs were more likely to have higher vIGA-AD scores than NH-Whites (OR = 1.57; P < 0.01). Non-Hispanic Blacks also had higher vIGA-AD scores than NH-Whites (OR = 1.42; P < 0.05) when controlling for all covariates other than treatment type (P < 0.05), adjustment for which renders the estimated black–white disparity nonsignificant. (OR = 1.32, P = 0.11). Descriptively comparing patient-reported outcome distributions identified no significant differences (P > 0.12). Despite presenting with more severe disease, Blacks and Hispanics have significantly lower odds of using advanced systemic therapy relative to NH-Whites, suggestive of an access disparity leading to disparities in disease control. These disadvantages persist after adjusting for an array of demographic, socioeconomic and medical history characteristics. The results highlight real-world evidence of racial and ethnic disparities among patients with AD.

Efficacy and Safety of Abrocitinib in Patients with Severe and/or Difficult-to-Treat Atopic Dermatitis: A Post Hoc Analysis of the Randomized Phase 3 JADE COMPARE Trial.

Traditional systemic immunosuppressants and advanced therapies improve signs and symptoms of moderate-to-severe atopic dermatitis (AD). However, data are limited in severe and/or difficult-to-treat AD. In the phase 3 JADE COMPARE trial of patients with moderate-to-severe AD receiving background topical therapy, once-daily abrocitinib 200mg and 100mg showed significantly greater reductions in the symptoms of AD than placebo and significantly greater improvement in itch response (with abrocitinib 200mg) than dupilumab at week2. This study assessed the efficacy and safety of abrocitinib and dupilumab in a subset of patients with severe and/or difficult-to-treat AD in a posthoc analysis of the JADE COMPARE trial. Adults with moderate-to-severe AD received once-daily oral abrocitinib 200mg or 100mg, dupilumab 300mg subcutaneous injection every 2weeks, or placebo with concomitant medicated topical therapy. Severe and/or difficult-to-treat AD subgroups were classified by baseline characteristics [Investigator's Global Assessment (IGA) 4, Eczema Area and Severity Index (EASI) > 21, failure or intolerance to prior systemic agents (excluding patients who took only corticosteroids), percentage of body surface area (%BSA) > 50, upper quartiles of EASI (EASI > 38) and %BSA (%BSA > 65), and combined subgroup of IGA 4, EASI > 21, and %BSA > 50, and failure or intolerance to prior systemic agents (excluding patients who took only corticosteroids)]. Assessments included IGA score of 0 (clear) or 1 (almost clear) and a ≥2-point improvement from baseline, ≥75% and ≥90% improvement from baseline in EASI (EASI-75 and EASI-90), ≥4-point improvement from baseline in Peak Pruritus-Numerical Rating Scale (PP-NRS4), time to PP-NRS4, least squares mean (LSM) change from baseline in 14-day PP-NRS (days2-15), Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI) up to week16. The proportion of patients achieving IGA 0/1, EASI-75, and EASI-90 responses was significantly greater with abrocitinib 200mg than placebo (nominal p <0.05) across all subgroups with severe and/or difficult-to-treat AD. Across most subgroups, PP-NRS4 response was significantly greater with abrocitinib 200mg than placebo (nominal p <0.01); the time to achieve this response was shorter with abrocitinib 200mg (range 4.5-6.0days) than abrocitinib 100mg (range 5.0-17.0days), dupilumab (range 8.0-11.0 days), and placebo (range 3.0-11.5days). LSM change from baseline in POEM and DLQI was significantly greater with abrocitinib 200mg than placebo (nominal p <0.001) across all subgroups. Clinically meaningful differences were observed between abrocitinib and dupilumab for most evaluated endpoints across several subgroups, including in patients who failed or were intolerant to prior systemic therapy. Abrocitinib provided rapid and substantially greater improvements in skin clearance and quality of life compared with placebo and dupilumab in subgroups of patients with severe and/or difficult-to-treat AD. These findings support the use of abrocitinib for severe and/or difficult-to-treat AD. ClinicalTrials.gov, NCT03720470.

Analysis of the development dynamics of cough syndrome in acute nasopharyngitis with intoxication syndrome

Introduction. Although acute cough in acute inflammatory diseases of the upper respiratory tract seems to be a minor problem and can be stopped on its own, it holds the leading position among all reasons for population receiving health care due to significant decrease in life quality.Purpose. To analyze the cough severity in patients with acute nasopharyngitis with intoxication syndrome in the treatment of systemic non-steroidal anti-inflammatory drugs (NSAIDs) and local interferon therapy.Materials and methods. The study included 62 patients with acute nasopharyngitis with intoxication syndrome, in the period from the onset of the first symptoms to the visit to the doctor was no more than 24 hours. They were divided into 2 groups: group 1 − 32 people (14 men, 18 women, age 34.4 ± 10.3 years) received traditional systemic therapy with NSAIDs, group 2 − 30 people (13 men, 17 women, age 41.1 ± 13.7 years) received interferon-α2b intranasally. Cough severity was assessed using a 3-point visual analog scale (VAS) on the day of admission and for the next 7 days.Results. On the 1st day dry cough was observed in 62.5–63.3% of cases. Starting from the 3rd day of observation, there were statistically significant differences in the intensity of this symptom between the groups. In the traditional therapy of NSAIDs, an increase in the number of patients with a complaint of cough, and an increase in its severity compared with the first day of observation was revealed. They lasted until the 6th day of illness, which was explained by the spread of the inflammatory process to the trachea and bronchi. In the treatment of local interferon therapy, cough regression was noted on day 4 in 83.3% of cases, with its complete disappearance in this group on day 6. The total duration of cough in group 1 was 6.0 (5.0; 8.0) days, in group 2 – 2.0 (1.0; 3.0) days.Conclusion. In acute inflammatory diseases of the upper respiratory tract, cough in the absence of prescribing drugs that affect this symptom persists on the eighth day of observation in 56.2% of patients with traditional therapy with systemic NSAIDs.

JAK Inhibitor Safety Compared to Traditional Systemic Immunosuppressive Therapies.

Dermatologists treating atopic dermatitis are interested in the safety profile of the recently available JAK inhibitors, upadacitinib and abrocitinib, especially after they received boxed safety warnings. Long-term clinical trial data using these JAK inhibitors for the treatment of atopic dermatitis suggest that they are associated with very low incidence rates of malignancy, major adverse cardiac events, and thromboembolic events. However, a knowledge gap exists regarding the incidence of adverse events for JAK inhibitors compared to traditional systemic therapies used to treat poorly controlled atopic dermatitis as well as baseline rates in both atopic dermatitis and reference control populations. To address this gap, we analyzed data regarding adverse events of special interest for methotrexate, cyclosporine, and systemic corticosteroids and calculated the incidence of adverse events per 100 patient-years for these drugs. We also examined data regarding baseline incidence of adverse events in atopic dermatitis and control patients. We found that compared to upadacitinib and abrocitinib, traditional systemic therapies for atopic dermatitis demonstrated equal or higher incidence rates for malignancy (excluding non-melanoma skin cancer), non-melanoma skin cancer, major adverse cardiac events, and venous thromboembolism. Moreover, the use of upadacitinib and abrocitinib also exhibited either comparable or lower incidence of malignancy (excluding non-melanoma skin cancer), major adverse cardiac events, and venous thromboembolism, but higher rates of non-melanoma skin cancer, in comparison to baseline rates in atopic dermatitis or control patients. These findings indicate that JAK inhibitors should be positioned, at least based on safety, ahead of traditional systemic therapies for atopic dermatitis treatment.J Drugs Dermatol. 2022;21(12):1298-1303. doi:10.36849/JDD.7187.

Glioblastoma microenvironment and its reprogramming by oncolytic virotherapy.

Glioblastoma (GBM), a highly aggressive form of brain tumor, responds poorly to current conventional therapies, including surgery, radiation therapy, and systemic chemotherapy. The reason is that the delicate location of the primary tumor and the existence of the blood-brain barrier limit the effectiveness of traditional local and systemic therapies. The immunosuppressive status and multiple carcinogenic pathways in the complex GBM microenvironment also pose challenges for immunotherapy and single-targeted therapy. With an improving understanding of the GBM microenvironment, it has become possible to consider the immunosuppressive and highly angiogenic GBM microenvironment as an excellent opportunity to improve the existing therapeutic efficacy. Oncolytic virus therapy can exert antitumor effects on various components of the GBM microenvironment. In this review, we have focused on the current status of oncolytic virus therapy for GBM and the related literature on antitumor mechanisms. Moreover, the limitations of oncolytic virus therapy as a monotherapy and future directions that may enhance the field have also been discussed.

Latest combination therapies in psoriasis: Narrative review of the literature.

Biological therapies revolutionized the treatment of many chronic inflammatory skin diseases, first of all psoriasis, thanks to their high efficacy and the reduced number of side effects. However, the use of a single biologic drug does not always provide complete control of the disease or associated comorbidities over time. The first biological drugs used for the treatment of psoriasis, tumor necrosis factor alpha inhibitors, have long been used in combination with traditional topical and systemic therapies to induce a complete remission of the disease that could not be achieved with innovative drug alone. Even with the advent of new biological therapies with more precise molecular targets, the challenge of using combination therapies remained. Psoriatic patients often have major comorbidities, such as arthritis, inflammatory bowel disease, uveitis or have other concomitant conditions such as chronic spontaneous urticaria and atopic dermatitis, which may require different biologic treatments than those indicated in psoriasis. The objective of this article is, through a comprehensive revision of the literature, to analyze in which cases the use of the combination of the latest therapies for psoriasis may be useful.

Non-alcoholic fatty liver disease-related hepatocellular carcinoma: Is there a role for immunotherapy?

Hepatocellular carcinoma (HCC) is among the most common cancers and it is a major cause of cancer-related deaths. Non-alcoholic fatty liver disease (NAFLD) affects approximately one fourth of individuals worldwide and it is becoming one of the most important causes of HCC. The pathogenic mechanisms leading to NAFLD-related HCC are complex and not completely understood. However, metabolic, fibrogenic, oncogenic, inflammatory and immunological pathways seem to be involved. First-line therapy of advanced HCC has recently undergone major changes, since the combination of atezolizumab and bevacizumab was proven to increase survival when compared to sorafenib. Other immune-oncology drugs are also demonstrating promising results in patients with advanced HCC when compared to traditional systemic therapy. However, initial studies raised concerns that the advantages of immunotherapy might depend on the underlying liver disease, which seems to be particularly important in NAFLD-related HCC, as these tumors might not benefit from it. This article will review the mechanisms of NAFLD-related hepatocarcinogenesis, with an emphasis on its immune aspects, the efficacy of traditional systemic therapy for advanced NAFLD-related HCC, and the most recent data on the role of immunotherapy for this specific group of patients, showing that the management of this condition should be individualized and that a general recommendation cannot be made at this time.

Circulating tumour cell gene expression and chemosensitivity analyses: predictive accuracy for response to multidisciplinary treatment of patients with unresectable refractory recurrent rectal cancer or unresectable refractory colorectal cancer liver metastases

BackgroundPatients with unresectable recurrent rectal cancer (RRC) or colorectal cancer (CRC) with liver metastases, refractory to at least two lines of traditional systemic therapy, may receive third line intraarterial chemotherapy (IC) and targeted therapy (TT) using drugs selected by chemosensitivity and tumor gene expression analyses of liquid biopsy-derived circulating tumor cells (CTCs).MethodsIn this retrospective study, 36 patients with refractory unresectable RRC or refractory unresectable CRC liver metastases were submitted for IC and TT with agents selected by precision oncotherapy chemosensitivity assays performed on liquid biopsy-derived CTCs, transiently cultured in vitro, and by tumor gene expression in the same CTC population, as a ratio to tumor gene expression in peripheral mononuclear blood cells (PMBCs) from the same individual. The endpoint was to evaluate the predictive accuracy of a specific liquid biopsy precision oncotherapy CTC purification and in vitro culture methodology for a positive RECIST 1.1 response to the therapy selected.ResultsOur analyses resulted in evaluations of 94.12% (95% CI 0.71–0.99) for sensitivity, 5.26% (95% CI 0.01–0.26) for specificity, a predictive value of 47.06% (95% CI 0.29–0.65) for a positive response, a predictive value of 50% (95% CI 0.01–0.98) for a negative response, with an overall calculated predictive accuracy of 47.22% (95% CI 0.30–0.64).ConclusionsThis is the first reported estimation of predictive accuracy derived from combining chemosensitivity and tumor gene expression analyses on liquid biopsy-derived CTCs, transiently cultured in vitro which, despite limitations, represents a baseline and benchmark which we envisage will be improve upon by methodological and technological advances and future clinical trials.

Integration of Genomic Biology Into Therapeutic Strategies of Gastric Cancer Peritoneal Metastasis.

The peritoneum is a common site of metastasis in advanced gastric cancer (GC). Diagnostic laparoscopy is now routinely performed as part of disease staging, leading to an earlier diagnosis of synchronous peritoneal metastasis (PM). The biology of GCPM is unique and aggressive, leading to a dismal prognosis. These tumors tend to be resistant to traditional systemic therapy, and yet, this remains the current standard-of-care recommended by most international clinical guidelines. As this is an area of unmet clinical need, several translational studies and clinical trials have focused on addressing this specific disease state. Advances in genomic sequencing and molecular profiling have revealed several promising therapeutic targets and elucidated novel biology, particularly on the role of the surrounding tumor microenvironment in GCPM. Peritoneal-specific clinical trials are being designed with a combination of locoregional therapeutic strategies with systemic therapy. In this review, we summarize the new knowledge of cancer biology, advances in surgical techniques, and emergence of novel therapies as an integrated strategy emerges to address GCPM as a distinct clinical entity.

Extravascular Cooling of Blood Using a Concentrated Thermoelectric Cooling Probe

Abstract Thermal therapies have strong potential for improving outcomes for patients suffering from cardiac arrest, neonatal hypoxic-ischemic encephalopathy, or medically refractory intracranial hypertension. We propose a novel tool to manipulate blood temperature through extravascular thermoelectric heat exchange of blood vessel walls and flowing blood. This tool is a concentrated cooling probe with several thermoelectric units combined to focus cooling at the application site. Using this tool, we aim to achieve desired levels of temperature control and potentially reduce complications associated with traditional intravascular or systemic thermal therapies. Leveraging the feedback control, speed, and reversible operation of thermoelectric cooling modules, the device can adapt to cool or heat as desired. Preclinical testing on rodent models confirmed rapid, significant reduction of intravenous jugular blood temperature when a prototype device was brought in contact with the left carotid artery (change in blood temperature of −4.74 ± 2.9 °C/h and −4.29 ± 1.64 °C/h for 0 °C and −5 °C cooling trials, respectively). Declines in rectal temperature were also noted, but at lesser magnitudes than for jugular blood (0 °C: −3.09 ± 1.29 °C/h; −5 °C: −2.04 ± 1.08 °C/h), indicating proof-of-concept of thermoelectric extravascular blood cooling within a relatively localized region of the body. With further improvements in the technique, there is potential for selective organ cooling via a reduction in the temperature of flowing blood.