Predictors for the use of systemic therapy in stage IB Mycosis fungoides.

BACKGROUND: The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is aprospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) inpatients with newly diagnosed mycosis fungoides (MF). OBJECTIVES: To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB)staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures. METHODS: In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centresin 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review. RESULTS: The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81·5%), while a smallerpercentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariateanalysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA,20%; IA-IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs.T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first-line SDT was 73%,while the ORR to first-line systemic treatments was lower (57%) (P = 0·027). Health-related QoL improvedsignificantly both in patients with responsive disease and in those with stable disease. CONCLUSIONS: Disease characteristics such as presence of plaques and FMF influence physician treatment choices,and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, futuretreatment guidelines for early-stage MF need to address these issues.

Prognostic value of FGFR2 alterations in patients with iCCA undergoing surgery or systemic treatments: A meta-analysis.

BACKGROUND: Over recent years, there has been a notable rise in the incidence of intrahepatic cholangiocarcinoma (iCCA), which presents a significant challenge in treatment due to its complex disease characteristics and prognosis. Notably, the identification of fibroblast growth factor receptor 2 (FGFR2) fusion/rearrangement, a potential oncogenic driver primarily observed in iCCA, raises questions about its impact on the prognostic outcomes of patients undergoing surgical intervention or other therapeutic approaches. METHODS: A comprehensive search from inception to July 2023 was conducted across PubMed, Embase, Web of Science, and the Cochrane Library databases. The objective was to identify relevant publications comparing the prognosis of FGFR2 alterations and no FGFR2 alterations groups among patients with iCCA undergoing surgical resection or other systemic therapies. The primary outcome indicators, specifically Overall Survival (OS) and Disease-Free Survival (DFS), were estimated using Hazard Ratios (HRs) with 95% confidence intervals (CIs), and statistical significance was defined as p < .05. Study quality was assessed using the Newcastle-Ottawa Quality Assessment Scale. Statistical analyses were performed using Review Manager 5.4 software and Stata, version 12.0. RESULTS: Six studies, involving 1314 patients (FGFR2 alterations group n = 173 and no FGFR2 alterations group n = 1141), were included in the meta-analysis. The analysis revealed that the FGFR2 alterations group exhibited a significantly better OS prognosis compared to the no FGFR2 alterations group, with a fixed-effects combined effect size HR = 1.31, 95%CI = 1.001-1.715, p = .049. Furthermore, meta-regression and subgroup analysis showed that the length of the follow-up period did not introduce heterogeneity into the results. This finding indicates the stability and reliability of the study outcomes. CONCLUSION: The current study provides compelling evidence that FGFR2 alterations are frequently associated with improved survival outcomes for patients with iCCA undergoing surgical resection or other systemic treatments. Additionally, the study suggests that FGFR2 holds promise as a safe and dependable therapeutic target for managing metastatic, locally advanced or unresectable iCCA. This study offers a novel perspective in the realm of targeted therapy for iCCA, presenting a new and innovative approach to its treatment.

Surgical outcomes and prognosis of HER2+ invasive breast cancer patients with a DCIS component treated with breast-conserving surgery after neoadjuvant systemic therapy.

INTRODUCTION: In up to 72 % of HER2+ invasive breast cancer (IBC), a ductal carcinoma in situ (DCIS) component is present. The presence of DCIS is associated with increased positive surgical margins after breast-conserving surgery (BCS). The aim of this study was to assess surgical margins, recurrence and survival in a nationwide cohort of HER2+ IBC with versus without a DCIS component, treated with neoadjuvant systemic therapy (NST) and BCS. MATERIALS AND METHODS: Women diagnosed with HER2+ IBC treated with NST and BCS, between 2010 and 2019, were selected from the Netherlands Cancer Registry and linked to the Dutch Nationwide Pathology Databank. Kaplan-Meier and Cox regression analyses were performed to determine locoregional recurrence rate (LRR) and overall survival (OS) and associated clinicopathological variables. Surgical outcomes and prognosis were compared between IBC only and IBC+DCIS. RESULTS: A total of 3056 patients were included: 1832 with IBC and 1224 with IBC+DCIS. Patients with IBC+DCIS had significantly more often positive surgical margins compared to IBC (12.8 % versus 4.9 %, p < 0.001). Five-year LRR was significantly higher in patients with IBC+DCIS compared to IBC (6.8 % versus 3.6 %, p < 0.001), but the presence of DCIS itself was not significantly associated with LRR after adjusting for confounders in multivariable analysis. Five-year OS did not differ between IBC+DCIS and IBC (94.9 % versus 95.7 %, p = 0.293). CONCLUSION: The presence of DCIS is associated with higher rates of positive surgical margins, but not with LRR and lower OS when adjusted for confounders. Further research is necessary to adequately select IBC+DCIS patients for BCS after NST.

When does a melanoma metastasize? Implications for management.

Selecting which patients with clinically-localized melanoma require treatment other than wide excision of the primary tumor is based on the risk or presence of metastatic disease. This in turn is linked to survival. Knowing if and when a melanoma is likely to metastasize is therefore of great importance. Several studies employing a range of different methodologies have suggested that many melanomas metastasize long before the primary lesion is diagnosed. Therefore, waiting for dissemination of metastatic disease to become evident before making systemic therapy available to these patients may be less effective than giving them post-operative adjuvant therapy initially if the metastatic risk is high. The identification of these high-risk patients will assist in selecting those to whom adjuvant systemic therapy can most appropriately be offered. Further studies are required to better identify high-risk patients whose primary melanoma is likely to have already metastasized.

Phase 2 study of neoadjuvant enzalutamide and paclitaxel for luminal androgen receptor-enriched TNBC: Trial results and insights into "ARness".

Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in neoadjuvant therapy (NAT) are yet to be determined. We tested the combination of the AR inhibitor enzalutamide (120 mg daily by mouth) and paclitaxel (80 mg/m2 weekly intravenously) (ZT) for 12 weeks as NAT for LAR-enriched TNBC. Eligibility criteria included a percentage of cells expressing nuclear AR by immunohistochemistry (iAR) of at least 10% and a reduction in sonographic volume of less than 70% after four cycles of doxorubicin and cyclophosphamide. Twenty-four patients were enrolled. Ten achieved a pathologic complete response or residual cancer burden-I. ZT was safe, with no unexpected side effects. An iAR of at least 70% had a positive predictive value of 0.92 and a negative predictive value of 0.97 in predicting LAR-enriched TNBC according to RNA-based assays. Our data support future trials of AR blockade in early-stage LAR-enriched TNBC.

Active Surveillance in Metastatic Renal Cell Carcinoma.

Metastatic renal cell carcinoma (mRCC) is a heterogenous disease with a variable clinical course. While therapies for treatment of this condition have progressed, they are not without toxicity. In some patients, active surveillance (AS) of this disease is increasingly considered to delay its toxicity. This article seeks to review the literature and discuss management of metastatic renal cell carcinoma, specifically regarding upfront AS, the role of radiation therapy in delaying systemic therapy, and surveillance after initial treatment with systemic therapy. Median time on AS prior to initiation of systemic therapy ranged from 14 to 60 months across studies. AS is appropriate to offer in favorable or intermediate risk, asymptomatic, and systemic treatment naïve patients with mRCC.

Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase 3 CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group.

BACKGROUND: Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor. PATIENTS AND METHODS: This randomized phase 3 trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1:1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098. RESULTS: Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n= 103 without upfront PTR, n=101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (IQR 59-71). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% CI 16.0-22.2) compared to 20.1 months (95% CI 17.0-25.1) in the upfront PTR arm (p = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (p=0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm. CONCLUSION: of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care.

Disease severity, treatment patterns, and quality of life in patients with moderate-to-severe psoriasis routinely managed with systemic treatment: results of the CRYSTAL observational study in Central and Eastern European countries.

Psoriasis is a common, life-long skin disease with a significant negative health and societal impact. Data on rates of disease control and treatment strategies are lacking in Central and Eastern European countries. We aimed to describe the real-world disease severity, control, and treatment strategies for psoriasis in patients from Central and Eastern European countries. CRYSTAL (EUPAS36459) was a cross-sectional, retrospective study in adults (18-75 years) from Bulgaria, Estonia, Hungary, Latvia, Lithuania, Romania, and Russia. We enrolled patients with moderate-to-severe psoriasis receiving continuous systemic treatment for ≥24 weeks. We used the Psoriasis Area and Severity Index (PASI) to describe disease severity and the Dermatology Life Quality Index (DLQI) to assess quality of life (QoL) and collected other outcomes [psoriasis work productivity and activity impairment (WPAI-PSO), patient satisfaction] at enrollment. Analyses were descriptive. A total of 690 patients were included in the analyses. Median disease duration was 11.8 years. Current treatment was monotherapy for most patients (95.8%) with either biological (BIO group; 88.4%) or conventional (NON-BIO group; 7.4%) agents. Mean (± standard deviation) absolute PASI scores were 3.5 ± 5.7, 3.1 ± 5.3, and 6.6 ± 7.4 in the overall population, the BIO group, and the NON-BIO group, respectively. Among patients treated with monotherapy, absolute PASI scores ≤1, ≤3, and ≤5 were observed for 44.1%, 72.0%, and 82.6% of BIO patients and 21.6%, 33.3%, and 49.0% of NON-BIO patients. Mean DLQI total score was 3.3 ± 5.1; higher scores were noted for higher absolute PASI. The most impacted WPAI-PSO domain was presenteeism; for all domains, impact increased with increased absolute PASI. A total of 91.8% of BIO patients and 74.5% of NON-BIO patients were satisfied with the current treatment. We observed a better disease control in BIO than NON-BIO patients. However, around half of BIO patients did not reach clear skin status and reported an impact on QoL. An improvement in treatment strategies is still needed in Central and Eastern European countries to optimize outcomes of moderate-to-severe psoriasis.

Quality of reporting and concordance between sources of adverse events in the treatment of moderate-to-severe psoriasis: a cross-sectional study of RCTs from a Cochrane systematic review.

OBJECTIVES: Incomplete reporting of safety outcomes in quality and availability of safety reporting in published articles of randomized clinical trials (RCTs) were described in different medical areas. The number of RCTs assessing systemic treatments for psoriasis has increased considerably. Complete and precise reporting of safety is mandatory for the efficacy/harms balance evaluation. We aimed to assess the quality and availability of safety reporting in published RCTs assessing systemic treatments for psoriasis, as well as the concordance of data between published trials and clinicaltrials.gov (CT). STUDY DESIGN AND SETTING: We included all RCTs in adults initiated after September 2009, assessing systemic psoriasis treatments compared with placebo or with an active comparator. All trials were selected in duplicate by two independent authors from the latest search of the dedicated Cochrane review. We described quality of safety reporting for all published RCTs, using a modified CONSORT harms scale by using descriptive analysis, and a composite score of 3 key items of safety report. For each RCT, data on adverse events (AEs)/serious AEs (SAEs) were extracted from the publication and CT: total number of AEs/SAEs, patients with AEs/SAEs, SAEs by system organ class classification and deaths. These data were compared between sources for each RCT. RESULTS: In total, 128 trials were included in the analysis of reporting quality, and 76 in the analysis of data concordance between sources. The median number of reported CONSORT harms items per article was 9 out of 18 (IQR 7-10), and mean number was 8.39 (sd = 3.02). Items in the methods section were the least frequently reported. The proportion of RCTs reporting the number of SAEs and death were significantly higher on ClinicalTrials.gov than in the published article ((100% (76/76) vs 88.2%, McNemar test, p <0.0016). At least one discrepancy between sources for SAE safety data was found in 30/76 (39.5%) RCTs. DISCUSSION: Shortcomings and gaps in the quality of safety reporting in publications of RCTs of systemic psoriasis treatments have been identified. A lack of data in published articles and discrepancies between published articles and CT data complete this finding.

Cross-sectional study of therapy-related expectations/concerns of patients with metastatic renal cell carcinoma and physicians in Japan.

OBJECTIVE: To achieve patient-centricity in metastatic renal cell carcinoma (mRCC) treatment, it is essential to clarify the differences in perspectives between patients and physicians. This cross-sectional analysis of a web survey aimed to clarify the differences in expectations and concerns between mRCC patients and physicians regarding systemic mRCC therapy in Japan. METHODS: Surveys from 83 patients and 165 physicians were analyzed. RESULTS: The top three most significant differences in expectations of systemic therapy between patients and physicians (patient-based physician value) were "Chance of achieving treatment-free status" (-30.1%, p < 0.001), "Longer survival" (+25.8%, p < 0.001), and "Chance of eliminating all evidence of disease" (-25.6%, p < 0.001). The top three most significant differences in concerns for systemic therapy between patients and physicians (patient-based physician value) were "Lack of efficacy" (+36.1%, p < 0.001), "Lack of knowledge of treatment" (-28.2%, p < 0.001), and "Daily activities affected by side effects" (+22.3%, p < 0.001). Diarrhea, fatigue/malaise, and nausea/vomiting were patients' most distressing adverse events; 50.6% of patients had difficulty telling their physicians about adverse events such as fatigue, anxiety, and depression. CONCLUSIONS: This study demonstrated a gap between patients with mRCC and physicians in their expectations and concerns for systemic therapy. Japanese patients with mRCC suffer from a number of adverse events, some of which are not shared with physicians. This study highlights the importance of communicating well with patients in clinical practice to achieve patient-centricity in systemic treatment for mRCC.

Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a high mortality neoplasm which usually appears on a cirrhotic liver. The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis. Notwithstanding the current deployment of treatments with curative intent (liver resection/local ablation and liver transplantation) in early and intermediate stages, a high rate of HCC recurrence persists, underscoring a pivotal clinical challenge. Emergent systemic therapies (ST), particularly immunotherapy, have demonstrate promising outcomes in terms of increase overall survival, but they are currently bound to the advanced stage of HCC. This review provides a comprehensive analysis of the literature, encompassing studies up to March 10, 2024, evaluating the impact of novel ST in the early and intermediate HCC stages, specially focusing on the findings of neoadjuvant and adjuvant regimens, aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent. We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent. Finally, we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

Atopic Dermatitis.

Atopic dermatitis (AD) is a common, chronic relapsing, and remitting inflammatory skin disease that is characterized by erythematous, scaly, and pruritic lesions often located over the flexural surfaces. Treatment goals of AD include the reduction of itching and burning, as well as the reduction of skin changes. Treatment of AD includes emollients and skin care, topical therapies including topical corticosteroids and steroid-sparing therapies, systemic therapies, and phototherapy.

Effectiveness and safety of systemic therapy for moderate-to-severe atopic dermatitis in children and adolescent patients: a systematic review.

Importance: Due to comorbidities and associated safety risks, the management of severe atopic dermatitis (AD) in pediatric and adolescent patients poses significant challenges. Objective: To examine the efficacy and safety of systemic therapies for the treatment of moderate-to-severe atopic dermatitis in children and adolescents. Evidence review: On Feb 29, 2024, a systematic literature search was conducted in Embase, PubMed, and the Cochrane Central Register of Controlled Trials (Central). No date restrictions were applied. Randomized clinical trials, cohort studies, large case series, and meta-analyses were assessed to evaluate the efficacy (or effectiveness) and/or safety of systemic treatments for moderate-to-severe atopic dermatitis in children and adolescents. Findings: A preliminary search yielded 1457 results, from which 19 unique articles with a total of 3741 patients were included in the analysis. Overall, the available data for each systemic medication are limited, and the overall quality of the included studies on conventional systemic treatments is relatively low. When Dupilumab was used as a standalone treatment, 30%-40% of infants and toddlers aged 6 months to 2 years achieved EASI-75, while 50% of patients aged 2 to 6 years achieved EASI-75. In children aged 6 to 12 years, 33.0%-59.0% of atopic dermatitis patients achieved EASI-75, and when combined with topical corticosteroids (TCS), 69.7%-74.6% achieved EASI-75. Long-term data showed EASI-75 rates ranging from 75.0% to 94.0% for this age group. For adolescents aged 12 to 18 years, 40%-71% of patients achieved EASI-75 within 12 to 16 weeks, and by week 52, 80.8% of patients achieved EASI-75.Abrocitinib treatment resulted in 68.5%-72.0% of patients achieving EASI-75. Omalizumab treatment at week 24 showed a percentage change in SCORAD scores of -12.4%. In the Methotrexate treatment group, there was a SCORAD change of -26.25% at week 12, while the Cyclosporine A group had a SCORAD change of -25.01%. Patients treated with IVIG (Intravenous Immunoglobulin) showed a -34.4% change in SCORAD percentage scores at week 4, which further decreased by 47.12% at week 24. Patients receiving 4mg of Baricitinib and TCS had a 52.5% rate of EASI-75 at 16 weeks, and patients receiving different doses of upadacitinib had a 63-75% rate of EASI-75 at 16 weeks. The rate of EASI-75 at 16 weeks was around 28% in patients who received various doses of Tralokinumab.The most common adverse events observed were nasopharyngitis, respiratory events and dermatitis atopic. Conclusions and relevance: Awareness of adverse events and concomitant medications is crucial, and appropriate dosing and frequent laboratory and clinical monitoring are also essential. More real-world evidence and prospective cohort studies analyzing the effectiveness and safety of systemic therapies in children and adolescents are of paramount importance for optimizing personalized, effective, and safe management of the growing population of patients with atopic dermatitis in this age group.

Discussion of ABC7 Consensus and German Recommendations.

The rationale behind the "International Consensus Conference for Advanced Breast Cancer" (ABC) is to standardize the treatment of patients with advanced or metastatic breast cancer worldwide using an evidence-based approach. The aim is also to ensure that patients in all countries receive adequate treatment based on current treatment recommendations and standards. The 7th International Consensus Conference on Advanced Breast Cancer (ABC7) took place from November 9 to 12, 2023 in Lisbon/Portugal. ABC7 focused on metastatic disease as well as on locally advanced and inflammatory breast cancer. Special topics included the treatment of oligometastatic patients, leptomeningeal disease, treatment of brain metastases, and pregnant women with ABC. As in previous years, patient advocates from all over the world participated in the consensus conference and were involved in decision making.

Hepatocellular carcinoma: Advances in systemic therapies.

Advanced hepatocellular carcinoma (HCC) is traditionally associated with limited treatment options and a poor prognosis. Sorafenib, a multiple tyrosine kinase inhibitor, was introduced in 2007 as a first-in-class systemic agent for advanced HCC. After sorafenib, a range of targeted therapies and immunotherapies have demonstrated survival benefits in the past 5 years, revolutionizing the treatment landscape of advanced HCC. More recently, evidence of novel combinations of systemic agents with distinct mechanisms has emerged. In particular, combination trials on atezolizumab plus bevacizumab and durvalumab plus tremelimumab have shown encouraging efficacy. Hence, international societies have revamped their guidelines to incorporate new recommendations for these novel systemic agents. Aside from treatment in advanced HCC, the indications for systemic therapy are expanding. For example, the combination of systemic therapeutics with locoregional therapy (trans-arterial chemoembolization or stereotactic body radiation therapy) has demonstrated promising early results in downstaging HCC. Recent trials have also explored the role of systemic therapy as neoadjuvant treatment for borderline-resectable HCC or as adjuvant treatment to reduce recurrence risk after curative resection. Despite encouraging results from clinical trials, the real-world efficacy of systemic agents in specific patient subgroups (such as patients with advanced cirrhosis, high bleeding risk, renal impairment, or cardiometabolic diseases) remains uncertain. The effect of liver disease etiology on systemic treatment efficacy warrants further research. With an increased understanding of the pathophysiological pathways and accumulation of clinical data, personalized treatment decisions will be possible, and the field of systemic treatment for HCC will continue to evolve.

Survival after docetaxel for metastatic castration-resistant prostate cancer in a rural health care setting.

Introduction: The aim of this study was to evaluate overall survival of men who received systemic therapy with docetaxel for metastatic castration- resistant prostate cancer (MCRPC) in rural Nordland County, Norway. Prognostic factors related to treatment and other variables were evaluated. Material and methods: Overall, 132 pa- tients were included in this retrospective study covering the years 2009-2022. Uni- and multivariate survival analyses were performed. Results: In this elderly cohort (median age 72 years), weekly low-dose docetaxel was the preferred regimen (44%). Seventy-three percent were treated in the first line. Only 11 patients (8%) were pre-exposed to docetaxel in the hormone-sensitive phase. Median survival was 14.3 months. Prognostic factors for longer survival included higher hemoglobin, lower lactate dehydrogenase, administration of docetaxel as first-line MCRPC treatment, and use of fewer prescription drugs for comorbidity. Pre-exposure to docetaxel did not play a major role, p = 0.76. Conclusions: In this rural health care setting, survival after docetaxel was shorter than reported by other groups. Blood test results were confirmed as important prognostic factors. In the present era of evolving treatment sequences, we recommend monitoring of real-world treatment results.

Evaluating Magnetic Seed Localization in Targeted Axillary Dissection for Node-Positive Early Breast Cancer Patients Receiving Neoadjuvant Systemic Therapy: A Comprehensive Review and Pooled Analysis.

Background/Objectives: De-escalation of axillary surgery is made possible by advancements in both neoadjuvant systemic therapy (NST) and in localisation technology for breast lesions. Magseed®, developed in 2013 by Dr. Michael Douk of Cambridge, United Kingdom, is a wire-free localisation technology that facilitates the localisation and retrieval of lymph nodes for staging. Targeted axillary dissection (TAD), which entails marked lymph node biopsy (MLNB) and sentinel lymph node biopsy (SLNB), has emerged as the preferred method to assess residual disease in post-NST node-positive patients. This systematic review and pooled analysis evaluate the performance of Magseed® in TAD. Methods: The search was carried out in PubMed and Google Scholar. An assessment of localisation, retrieval rates, concordance between MLNB and SLNB, and pathological complete response (pCR) in clinically node-positive patients post NST was undertaken. Results: Nine studies spanning 494 patients and 497 procedures were identified, with a 100% successful deployment rate, a 94.2% (468/497) [95% confidence interval (CI), 93.7-94.7] localisation rate, a 98.8% (491/497) retrieval rate, and a 68.8% (247/359) [95% CI 65.6-72.0] concordance rate. pCR was observed in 47.9% (220/459) ) [95% CI 43.3-52.6] of cases. Subgroup analysis of studies reporting the pathological status of MLNB and SLNB separately revealed an FNR of 4.2% for MLNB and 17.6% for SLNB (p = 0.0013). Mean duration of implantation was 37 days (range: 0-188). Conclusions: These findings highlight magnetic seed localisation's efficacy in TAD for NST-treated node-positive patients, aiding in accurate axillary pCR identification and safe de-escalation of axillary surgery in excellent responders.

American Academy of Dermatology Guidelines for Managing Atopic Dermatitis.

The American Academy of Dermatology first published a series of guidelines for diagnosing and managing atopic dermatitis in 2014. Twelve clinicians were selected to review, grade, and offer clinical insight on available data regarding the clinical features, symptomology, pathophysiology, education, treatment, and emerging clinical studies on atopic dermatitis (AD). Based on these findings, the AAD released a guideline to streamline information on atopic dermatitis for physicians, recommending using clinical evidence to diagnose and first treating with nonpharmacologic therapies to restore the natural skin barrier. Topical pharmacologic therapies were recommended for improving pruritus and inflammation and newer systemic agents for clinically relevant moderate-to-severe cases. Evidence-based practices were emphasized in comparison to those that lacked therapeutic data. To highlight the emerging evidence and pharmacologic breakthroughs in atopic dermatitis, the AAD produced an updated set of guidelines educating physicians on new agents and their role in treatment. This chapter reviews the AAD guidelines as a tool for managing atopic dermatitis and staying up to date on disease advancements.

The Impact of Sequential Therapies after First-Line Systemic Therapies in Unresectable Hepatocellular Carcinoma.

Background: The therapeutic options for hepatocellular carcinoma (HCC) have greatly expanded recently, and current first-line therapies include sorafenib, lenvatinib, and atezolizumab-bevacizumab. The aim of this study was to investigate the therapeutic efficacy of sequential systemic treatments after progressing to the first-line agent in patients with unresectable HCC. Methods: Data were collected from subjects with HCC, BCLC stage B or C, who received first-line sorafenib, lenvatinib, or atezolizumab-bevacizumab from September 2020 to December 2022. The patients who progressed after first-line therapy were evaluated according to individual clinical status in order to decide whether or not to accept sequential therapy. The clinical baseline characteristics and overall survival (OS) of enrolled patients were collected and further analyzed. Results: Among the 127 enrolled patients, percentage of sequential therapy was 67.9%, 21.6%, and 37.5% in those with tumor progression after first-line sorafenib, lenvatinib, or atezolizumab-bevacizumab, respectively. Acceptance of sequential therapy (HR 0.46, p = 0.041) and presentation of ALBI grade I (HR 0.36, p = 0.002) had a significantly positive impact on OS. Pre-treatment ALBI grade had a significant impact on the decision to accept sequential therapy in patients with progressed HCC. Conclusions: The patients who were able to undergo sequential therapy had a better survival outcome compared to those who received only one agent, and the pre-treatment ALBI level might be regarded as a cornerstone tool to assess survival outcomes in patients undergoing treatment for HCC.

The Current Role of Radiation in the Management of Cholangiocarcinoma-A Narrative Review.

Cholangiocarcinoma (CCA) is a rare cancer of bile ducts. It is associated with a poor prognosis. The incidence of CCA is rising worldwide. Anatomical subgroups have been used to classify patients for treatment and prognosis. There is a growing understanding of clinically important distinctions based on underlying genetic differences that lead to different treatment options and outcomes. Its management is further complicated by a heterogeneous population and relative rarity, which limits the conduct of large trials to guide management. Surgery has been the primary method of therapy for localized disease; however, recurrence and death remain high with or without surgery. Therefore, there have been concerted efforts to investigate new treatment options, such as the use of neoadjuvant treatments to optimize surgical outcomes, targeted therapy, leveraging a new understanding of immunobiology and stereotactic radiation. In this narrative review, we address the evidence to improve suboptimal outcomes in unresectable CCA with radiation, as well as the role of radiation in neoadjuvant and postoperative treatment. We also briefly discuss the recent developments in systemic treatment with targeted therapies and immune checkpoint inhibitors.