Systemic Treatment Of Patients Research Articles

A specific microRNA profile as predictive biomarker for systemic treatment in patients with metastatic colorectal cancer

BackgroundPalliative systemic therapy is currently standard of care for patients with extensive metastatic colorectal cancer (mCRC). A biomarker predicting chemotherapy benefit which prevents toxicity from ineffective treatment is urgently needed. Therefore, a previously developed tissue‐derived microRNA profile to predict clinical benefit from chemotherapy was evaluated in tissue biopsies and serum from patients with mCRC.MethodsSamples were prospectively collected from patients (N = 132) who were treated with capecitabine or 5‐FU/LV with oxaliplatin ± bevacizumab. Response evaluation was performed according to RECIST 1.1 after three or four cycles, respectively. Baseline tissue and serum miRNAs expression levels of miR‐17‐5p, miR‐20a‐5p, miR‐30a‐5p, miR‐92a‐3p, miR‐92b‐3p, and miR‐98‐5p were quantified with RT‐qPCR and droplet digital PCR, respectively. Combined predictive performance of selected variables was tested using logistic regression analysis.ResultsFrom 132 patients, 81 fresh frozen tissue biopsies from metastases and 93 serum samples were available. Based on expression levels of miRNAs in tissue, progressive disease could be predicted with an AUC of 0.85 (95% CI:0.72‐0.91) and response could be predicted with an AUC of 0.70 (95% CI:0.56‐0.80). This did not outperform clinical parameters alone (respectively P = .14 and P = .27). Expression levels of miR‐92a‐3p and miR‐98‐5p in serum significantly improved the predictive value of clinical parameters for response to chemotherapy (AUC 0.74, 95% CI:0.64‐0.84, P = .003) in this cohort.ConclusionsThe additive predictive value to clinical parameters of the tissue‐derived six miRNA profile for clinical benefit could not be validated in patients with mCRC treated with first‐line systemic therapy. Although miR‐92a‐3p and miR‐98‐5p serum levels improved the predictive value of clinical parameters, it remained insufficient for clinical decision‐making.

Novel molecular targets in hepatocellular carcinoma.

Globally, hepatocellular carcinoma (HCC) is a leading cause of cancer and cancer-related deaths. The therapeutic efficacy of locoregional and systemic treatment in patients with advanced HCC remains low, which results in a poor prognosis. The development of sorafenib for the treatment of HCC has resulted in a new era of molecular targeted therapy for this disease. However, the median overall survival was reported to be barely higher in the sorafenib treatment group than in the control group. Hence, in this review we describe the importance of developing more effective targeted therapies for the management of advanced HCC. Recent investigations of molecular signaling pathways in several cancers have provided some insights into developing molecular therapies that target critical members of these signaling pathways. Proteins involved in the Hedgehog and Notch signaling pathways, Polo-like kinase 1, arginine, histone deacetylases and Glypican-3 can be potential targets in the treatment of HCC. Monotherapy has limited therapeutic efficacy due to the development of inhibitory feedback mechanisms and induction of chemoresistance. Thus, emphasis is now on the development of personalized and combination molecular targeted therapies that can serve as ideal therapeutic strategies for improved management of HCC.

Consensus statements on PSMA PET/CT response assessment criteria in prostate cancer

PurposeProstate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is used for (re)staging prostate cancer (PCa) and as a biomarker for evaluating response to therapy, but lacks established response criteria. A panel of PCa experts in nuclear medicine, radiology, and/or urology met on February 21, 2020, in Amsterdam, The Netherlands, to formulate criteria for PSMA PET/CT-based response in patients treated for metastatic PCa and optimal timing to use it.MethodsPanelists received thematic topics and relevant literature prior to the meeting. Statements on how to interpret response and progression on therapy in PCa with PSMA PET/CT and when to use it were developed. Panelists voted anonymously on a nine-point scale, ranging from strongly disagree (1) to strongly agree (9). Median scores described agreement and consensus.ResultsPSMA PET/CT consensus statements concerned utility, best timing for performing, criteria for evaluation of response, patients who could benefit, and handling of radiolabeled PSMA PET tracers. Consensus was reached on all statements. PSMA PET/CT can be used before and after any local and systemic treatment in patients with metastatic disease to evaluate response to treatment. Ideally, PSMA PET/CT imaging criteria should categorize patients as responders, patients with stable disease, partial response, and complete response, or as non-responders. Specific clinical scenarios such as oligometastatic or polymetastatic disease deserve special consideration.ConclusionsAdoption of PSMA PET/CT should be supported by indication for appropriate use and precise criteria for interpretation. PSMA PET/CT criteria should categorize patients as responders or non-responders. Specific clinical scenarios deserve special consideration.

Atopic dermatitis displays stable and dynamic skin transcriptome signatures

Skin transcriptome studies in atopic dermatitis (AD) showed broad dysregulation as well as "improvement" under therapy. These observations were mainly made in trials and based on microarray data. Our aim was to explore the skin transcriptome and the impact of systemic treatment in patients of the TREATgermany registry. Biopsy specimens from 59 patients with moderate-to-severe AD before and 30 patients 12 weeks after start of systemic treatment (dupilumab [n= 22] or cyclosporine [n= 8]) and from 31 healthy controls were subjected to mRNA sequencing. Differential expression, pathway enrichment, correlation, and coexpression network analysis were conducted. Both lesional and nonlesional skin showed a stable "core" signature characterized by disturbed epidermal differentiation and activation of IL-31/IL-1 signaling. Asecond dynamic signature showed progressive enrichment for type 2 inflammation, TH17 signaling, and natural killer cell function. Markers correlated with disease activity have functions in epidermal barrier properties and immune modulation. IL4RA was among the top 3 central dysregulated genes. Cyclosporine led to a more pronounced global transcriptome reversion and normalized TH17 cell/IL23 signaling, whereas dupilumab led to a stronger increase in level of epidermal differentiation markers. Both treatments strongly decreased levels of type 2 markers, but overall the residual profile was still profoundly different from that of healthy skin. Lower levels of IL4RA and IL13 and high IL36A expression were related to a stronger clinical response to dupilumab. The AD core signature is characterized by dysregulation of genes related to keratinocyte differentiation and itch signaling. Adynamic signature reflects progressive immune responses dominated by type 2 cytokines with an additional role of TH17 and natural killer cell signaling.

Systemic treatment of hepatocellular carcinoma: from sorafenib to combination therapies.

For almost a decade, systemic therapy of advanced hepatocellular carcinoma (HCC) was limited to the tyrosine kinase inhibitor (TKI) sorafenib. Different agents including checkpoint inhibitors, TKIs and anti-VEGFR antibodies demonstrated efficacy in treatment. For the first time, the combination of atezolizumab and bevacizumab, a first-line treatment that is superior to the current standard was identified, potentially changing the way we treat HCC. In this review, we summarize current data on systemic treatment of patients with advanced HCC, focusing on combination therapies comprising immune checkpoint inhibitors, TKIs and locoregional therapies. We elucidate findings from recent trials and discuss such challenges as the lack of predictive biomarkers for identification of subgroups that will benefit from novel treatment strategies.

Sequential systemic treatment in patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers. After many years of stagnation, there are now several systemic treatments available for patients with HCC. To analyse the feasibility and efficacy of sequential systemic treatments in patients with HCC in clinical practice. In this multicentre study, patients who were treated with novel systemic therapies for HCC between 2014 and 2019 at two referral centres, Hannover Medical School, Germany, and Medical University of Vienna, Austria, were included. Overall, 85 patients were included of which 76 patients (89.4%) received more than one and a maximum of five systemic treatment lines. The most common therapy sequence was sorafenib (n=72; 84.7%) followed by regorafenib (n=37; 48.7%), whereas 11 patients were initially treated with lenvatinib (12.9%). Other second-line treatments included pembrolizumab, nivolumab, cabozantinib and ramucirumab. Hepatic function deteriorated during sequential systemic treatment in 48.6% of the patients as defined by an increase in at least one Child-Pugh point. Median overall survival (mOS) from the start of first systemic treatment was 35months for patients with sequential systemic treatment compared to 9months forpatients with one systemic treatment line (P<0.001). Patients previously treated with surgical/locoregional therapies had a longer mOS compared to patients with initial systemic treatment (66 vs 25months; P=0.020). Sequential systemic treatment is feasible and effective in selected patients with HCC in clinical practice. Our study underlines the critical importance of well-preserved liver function for successful administration of sequential systemic therapy.

Molecular subtypes and clinical outcomes to initial systemic treatment in patients with small cell lung cancer.

9018 Background: Investigators have proposed that differential expression of the transcription regulators ASCL1 and NeuroD1 can be used to define molecular subtypes of small cell lung cancers (SCLCs). Here we evaluate SCLC subtypes based on ASCL1 and NeuroD1 expression in patients (pts) treated with first-line (1L) chemotherapy profiled with targeted next-generation sequencing (NGS). Methods: We used NGS (MSK-IMPACT) to profile tumors from pts with SCLCs. We performed IHC to assess ASCL1 (A) or NeuroD1 (N). Objective response rate (ORR) to therapy was determined using RECIST. PFS and OS were analyzed using Kaplan-Meier. Results: 281 pts with SCLCs were profiled with NGS (102 LS-SCLC; 179 ES-SCLC). Most frequently mutated genes were TP53 (90%), RB1 (68%), KMT2D (22%), NOTCH1 (15%), FAT1 (14%), PTPRD (12%). Mutations in BIRC3, FOXL2, TENT5C, TET1, NRAS, KIT, TSHR, ESR1 were enriched in ASCL1-/NeuroD1+ (A-/N+), and mutations in KMT2D and EP300 were enriched in A-/N- (p&lt;0.05). Copy number alterations in WWTR1, ATR, IKZF1, PALB2, PIK3CB were enriched in A-/N+ (p&lt;0.05). IHC for ASCL1 and NeuroD1 was performed on 78 samples: 11 A-/N-, 32 A+/N-, 4 A-/N+, 31 A+/N+. Overall survival at 1 year based on subtype was 25% in A-/N- (2/9), 60% in A-/N+ or A+/N- (13/32), and 55% in A+/N+ (10/25). For the 10 pts who survived 2 years, 5 were A+/N- and 5 were A+/N+. 146 pts treated with 1L platinum had RECIST-evaluable disease. ORR was 75% (110/146; 95% CI 68-82%). Median PFS was 7 months with CR/PR and 3.5 months with SD/PD (HR 0.32; 95% CI 0.18-0.56). Median OS was 17 months with CR/PR and 11 months with SD/PD (HR 0.55; 95% CI 0.34-0.9). Mutations in RUNX1, EPHA7, CDKN2A, FLT1 and copy number alterations in FGFR1, CCND1 were enriched in patients with SD/PD (p&lt;0.05). PFS rate at 6 months was 25% in A-N- (1/4), 60% in A-/N+ or A+/N- (9/15), and 55% in A+/N+ (6/11). For the 7 pts who survived 2 years, 3 were A+/N- and 4 were A+/N+. Conclusions: Molecular subtypes defined by ASCL1 and NeuroD1 encompass molecular characteristics that may predict patient outcomes. Further investigation is needed to delineate the underlying biological differences among the various subtypes to help define therapeutic vulnerabilities of each subtype of SCLC. Completion of IHC for ASCL1, NeuroD1 and additional key transcription factors POU2F3 and YAP1 are in progress for the entire cohort. WES and RNA sequencing are occurring in parallel and will be correlated with IHC results and clinical outcomes.

Systemic treatment of patients with solid tumors during the COVID-19 (SARS-CoV-2) pandemic — comprehensive recommendations of the Polish Society of Clinical Oncology

Systemic treatment of patients with solid tumors during the COVID-19 (SARS-CoV-2) pandemic — comprehensive recommendations of the Polish Society of Clinical Oncology

Sequential Systemic Treatment in Advanced Hepatocellular Carcinoma Is Able to Prolong Median Survival to More than 3 Years in a Selected Real-World Cohort

Introduction: The number of efficacious systemic agents for advanced hepatocellular carcinoma (HCC) has rapidly increased over the past 3 years. However, guidance for optimal sequential systemic treatment in patients with advanced disease and experience with outcome and safety profiles are lacking. Objective: We aimed to assess efficacy and tolerability of sequential systemic therapy of advanced HCC. Methods: Our single-center study prospectively followed 14 patients who received multiple, sequential systemic therapies after progression or intolerance to sorafenib. Endpoints were overall and progression-free survival (OS, PFS), objective response rate (ORR), and treatment-emergent adverse events (TEAE). Results: Patients had well-compensated liver function and good performance status at start of each systemic therapy. Agents included sorafenib (n = 14), regorafenib (n = 10), immunotherapy with nivolumab or pembrolizumab (n = 10), lenvatinib (n = 3), ramucirumab (n = 2), and others, with a median of 3 lines of systemic therapy per patient. Median OS was 37.4 months from initiation of first-line therapy with sorafenib. PFS and ORR for sorafenib, regorafenib, and immunotherapy were 6.6, 5.3, and 6.6 months, and 15.4, 11.1, and 22.2%, respectively. TEAE were frequent (46–80%), but mostly manageable during tyrosine kinase inhibitor therapy and without the need for termination in most patients. However, TEAE due to immunotherapy (60%) led to cessation of treatment in 40% of the patients. Conclusions: Sequential systemic therapy is able to prolong median OS in selected patients with advanced HCC to more than 3 years. TEAE are frequent, but manageable, and the quality of adverse events depends on the respective agent. Further investigation of potential predictive biomarkers for treatment allocation is needed.

Increased circulating tumor DNA as a noninvasive biomarker of early treatment response in patients with metastatic ovarian carcinoma: A pilot study.

Detection of circulating tumor DNA is a new noninvasive technique with potential roles in diagnostic, follow-up, and prognostic evaluation of patients with many types of solid tumors. We aimed to evaluate the role of circulating tumor DNA in the setting of metastatic ovarian carcinoma. A prospective cohort of patients with metastatic ovarian cancer who were referred to systemic therapy was enrolled. Blood samples were collected before the start of treatment and monthly thereafter for 6 months. Circulating tumor DNA was quantified by real-time quantitative reverse transcription polymerase chain reaction of different lengths of Arthrobacter luteus elements as described by Umetani et al. A total of 11 patients were included, 2 for primary disease and 9 for recurrent disease. After the first cycle of chemotherapy, patients whose circulating tumor DNA levels increased from baseline were more likely to respond to chemotherapy than those whose circulating tumor DNA levels did not increase (p = 0.035). Furthermore, patients whose circulating tumor DNA levels rose after the first cycle of chemotherapy also had improved disease-free survival compared to those whose circulating tumor DNA levels did not increase (p = 0.0074). We conclude that the increase in circulating tumor DNA values collected in peripheral blood after the first cycle of systemic treatment in patients with advanced ovarian cancer is associated with an early response to systemic treatment and correlates with superior disease-free survival in this population. Circulating tumor DNA might be a specific, noninvasive, and cost-effective new biomarker of early response to systemic treatment in these patients.

International and multicenter real-world study of sorafenib-treated patients with hepatocellular carcinoma under dialysis.

Information on safety and efficacy of systemic treatment in patients with hepatocellular carcinoma (HCC) under dialysis are limited due to patient exclusion from clinical trials. Thus, we aimed to evaluate the rate, prevalence, tolerability, and outcome of sorafenib in this population. We report a multicenter study comprising patients from Latin America and Europe. Patients treated with sorafenib were enrolled; demographics, dose modifications, adverse events (AEs), treatment duration, and outcome of patients undergoing dialysis were recorded. As of March 2018, 6156 HCC patients were treated in 44 centres and 22 patients were concomitantly under dialysis (0.36%). The median age was 65.5years, 40.9% had hepatitis C, 75% had Child-Pugh A, and 85% were Barcelona Clinic Liver Cancer-C. The median time to first dose modification, treatment duration and overall survival rate were 2.4months (interquartile ranges [IQR], 0.8-3.8), 10.8months (IQR, 4.5-16.9), and 17.5months (95% CI, 7.2-24.5), respectively. Seventeen patients required at least 1 dose modification. The main causes of first dose modification were asthenia/worsening of Eastern Cooperative Oncology Group-Performance Status and diarrhoea. At the time of death or last follow-up, four patients were still on treatment and 18 had discontinued sorafenib: 14 were due to tumour progression, 2 were sorafenib-related, and 2 were non-sorafenib-related AE. The outcomes observed in this cohort seem comparable to those in the non-dialysis population. Thus, to the best of our knowledge, this is the largest and most informative dataset regarding systemic treatment outcomes in HCC patients undergoing dialysis.

The Accuracy of Preoperative Axillary Ultrasound in the Diagnosis of Lymph Node Involvement at Motamed Cancer Institute, Iran

Background: Axillary lymph node (LN) status plays an important role in the local and systemic treatment of patients with breast cancer. Preoperative axillary ultrasound (AUS) is routinely used for the evaluation of axillary lymph nodes as a non-invasive method. Objectives: The purpose of this study was to evaluate the sensitivity and specificity of axillary ultrasound in comparison with pathology in a referral breast center. Methods: During a cross-sectional study all patients with breast cancer presenting to the imaging department between September 2015 and August 2016 were evaluated for axillary lymph node status by ultrasound. After comparing these results with the pathology of LNs, the sensitivity, specificity, and accuracy of the ultrasound in the diagnosis of axillary lymph node involvement were measured. Results: Overall 140 patients were enrolled in the study. The mean age of patients was 48.87 (± 10.46) years with an age range between 25 - 81 years. The sensitivity, specificity, and accuracy of the ultrasound were reported as 56%, 88%, and 76%, respectively. The highest sensitivity rate was related to AUS + Physical examination (PE) with 70%. The best specificity was for AUS, about 88%, and the accuracy of AUS+PE was the highest about 80%. Conclusions: The sensitivity of the AUS in the diagnosis of axillary involvement in the Motamed Cancer Institute was moderate and the specificity was good. The combination of physical examination and ultrasound could improve the sensitivity in comparison to each one alone. If both are suspicious, axillary dissection could be considered when fine needle aspiration (FNA) or core needle biopsy (CNB) of the lymph node is not available.

Temporal activation of WNT/\u03b2-catenin signaling is sufficient to inhibit SOX10 expression and block melanoma growth

Despite advances in the systemic treatment of patients with metastatic melanoma using immune checkpoint and tyrosine kinase inhibitors (TKI), the majority of stage IV melanoma patients eventually succumb to the disease. We have previously identified the transcription factor Sox10 as a crucial player in melanoma, yet the underlying molecular mechanisms mediating Sox10-dependent tumorigenesis remain largely uncharacterized. Here, we show that MEK and RAF inhibitors do not suppress levels of SOX10 protein in patient-derived cells in vitro, as well as in melanoma patients in vivo. In a search for pharmacological inhibitors of SOX10, we performed a mass spectrometry-based screen in human melanoma cells. Subsequent analysis revealed that SOX10 directly interacts with β-catenin, which is a key mediator of canonical Wnt/β-catenin signaling. We demonstrate that inhibitors of glycogen synthase kinase 3 alpha/beta (GSK3α/β) efficiently abrogate SOX10 protein in human melanoma cells in vitro and in melanoma mouse models in vivo. The mechanism of action of GSK3-mediated SOX10 suppression is transcription-independent and relies on the presence of a proteasome degradable form of β-catenin. Taken together, we provide evidence that activation of canonical Wnt signaling has a profound effect on melanoma growth and is able to counteract Sox10-dependent melanoma maintenance both in vitro and in vivo.

Systemic therapy and the use of complementary and alternative medicine in patients with recognized occupational hand eczema in Denmark: A cross-sectional questionnaire-based study.

Concerns have been raised that a chronic course of hand eczema (HE) could be fostered by a lack of efficient treatment at an early stage. First, to assess the prevalence of systemic treatment in patients with chronic occupational HE (OHE) and relate this to demographic data, HE severity, and atopic dermatitis (AD). Second, to explore the use of complementary and alternative medicine (CAM) in the same population. Baseline data were obtained from a registry-based study including patients with recognized OHE in a 2-year period in Denmark, comprising a total of 2703 workers. A follow-up questionnaire after 4 to 5 years included questions on disease severity and treatments. A total of 1565 participants responded to the questionnaire, and of these 1203 had ongoing HE at follow-up and were included in the study. In total, 10.0% had received systemic therapy, whereas this share was 13.3% in those with self-reported moderate-to-severe HE. Age >35 years, previous or current AD, and severe eczema were factors related to use of systemic treatment. Use of CAM was reported by 6.2% of the study population. We suggest that chronicity of HE may be perpetuated by the lack of efficient treatment.

Effect of biologics targeting interleukin-23/-17 axis on subclinical atherosclerosis: results of a pilot study.

Psoriasis is associated with an increased risk of developing atherosclerotic vascular disease. The hypothesis that treatment of the skin inflammation may decrease the risk of developing atherosclerosis and consequently, cardiovascular disease, is currently a focus of significant attention. To assess the effect of biologic drugs targeting the interleukin (IL)-23/IL-17 axis on selected subclinical atherosclerosis parameters in patients with psoriatic disease. In a series of patients with moderate to severe psoriasis who were eligible for biologic therapy, pulse wave velocity (PWV) and intima-media thickness (IMT) were determined before therapy and after 6months of treatment with biologics (ustekinumab, secukinumab, ixekizumab). After 6months of treatment, a marked clinical improvement of skin lesions was observed in all patients. No significant changes in PWV or IMT values were observed before (8.59±1.96mm and 0.54±0.9mm, respectively) and after 6months (8.89±2.02mm and 0.53±0.9mm) of therapy (P=0.16 and P=0.74). Systemic treatment of patients with a psoriatic disease with biologics targeting theIL-23/IL-17 axis has a possibly neutral effect on atherosclerosis. Additional studies are needed to assess the impact of newer biologic treatments on atherosclerosis.

Use of antidepressants and benzodiazepine-related hypnotics before and after initiation of TNF-\u03b1 inhibitors or non-biological systemic treatment in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis

BackgroundRheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are autoimmune disorders associated with an increased risk for depression, anxiety and sleeping problems. The objective of this study was to analyze use of antidepressants and benzodiazepine-related hypnotics (BRH) in Sweden before and after first time treatment with anti-TNF and non-biological systemic (NBS) treatments among patients with the above diagnoses, and to correlate such use with that of randomly selected population controls.MethodsPatients and dispensed drugs were identified in nationwide Swedish healthcare registers. Proportions of subjects filling prescriptions of antidepressants and BRH from 2 years before start of treatment (index-date), and 2 years after index date were assessed. Using the period -6 months to index-date as reference, prevalence rate ratios were computed for 6 months’ intervals before and after index. For up to ten randomly selected population controls per patient, the same measures were calculated.ResultsA total of 6256 patients started anti-TNF treatment, and 13,241 NBS treatment. The mean age at index was 52.0 for the anti-TNF group and 56.1 for NBS. Use of antidepressants and BRH was similar in both treatment groups (10.4–12.8%), significantly more common than in the controls (6.6 to 7.6%). For all patients, proportions filling prescriptions for antidepressants and BRH decreased directly or soon after the index; no such changes were seen in the controls, who all showed a slow but steady increase in use over time. Starters of anti-TNF treatment did not show clearer decreases in use of psychotropics than those initiating NBS.ConclusionsDecreased rates of dispensed psychotropic drugs after the time of anti-TNF and NBS treatment initiation were seen among patients with autoimmune disorders but not population controls. This may correspond to treatment effects of anti-TNF and NBS also on psychiatric symptoms among these patients.

Systemic treatment of patients with advanced cutaneous squamous cell carcinoma: response rates and outcomes of the regimes used

BackgroundCutaneous squamous cell carcinoma (cSCC) is the second most common type of skin cancer. Few patients with cSCC experience metastases, but the prognosis of advanced cSCC (acSCC) is dismal. Evidence regarding systemic therapy for acSCC is limited. Therefore, we aimed to determine the most effective systemic treatment for acSCC. Patients and methodsThis retrospective study involved 16 Japanese institutions. We documented patient and tumour characteristics and disease course of patients with acSCC who received systemic therapy between 1st January 2006 and 31st December 2015. We compared the overall survival (OS) and progression-free survival (PFS) for (1) platinum versus non-platinum groups, (2) radiation plus chemotherapy first-line therapy (RCT) versus non-RCT groups and (3) platinum-based RCT versus non–platinum-based RCT groups. ResultsAlthough the use of platinum-based systemic therapy was not associated with statistically significant improvements in PFS and OS, there were significant differences between the RCT and non-RCT groups (PFS: p < 0.001, OS: p = 0.003). In the subgroup analysis, RCT significantly prolonged PFS and OS in the nodal SCC (nSCC) group. For the RCT and non-RCT groups, the median OS was 110 and 14 months, respectively, and the 5-year OS rate was 54% and 21%, respectively. ConclusionRCT could improve OS in patients with nSCC. However, further multicenter prospective studies are needed to establish evidence for superiority of RCT.

Biosynthesis and Characterization of Zinc Oxide Nanoparticles for the Systemic Treatment of Patients with Lymphoma in Nursing Care

Zinc oxide (ZnO) nanoparticles recently are of significant consideration because of their applications as nontoxic metal oxides. This study is mainly intended to improve a simple, efficient, and environment-friendly method for preparation of ZnO nanoparticles. This process has been developed based on plant-intervened synthesis by making use of microwave Saturejahortensis aqueous extract. We have further characterized the obtained Zinc oxide nanoparticles by using different techniques. Additionally, their cytotoxic potential was inspected via MTT assay against both B lymphoma, A20 and T lymphoma, EL4 cells lines. The zinc oxide nanoparticle exposed cells for about 24 h showed diminished cell viability in the tested cell lines where EL4 cells has been reduced to 75% of control after 24 h, whereas A20 cells were lowered to 68% of control. ZnO-NPs have proficiently hindered EL4 cell DNA synthesis at 100 μg concentration whereas completely blocked the DNA proliferation at about 50 g concentration. However, A20 cells besides presented similar propensity, thus exploring the ZnO-NPs potential to treat lymphomas.

Systemic treatment of patients with early breast cancer: recent updates and state of the art

This review is focused on trials generating results that potentially impacted clinical practice since the 2017 St. Gallen Consensus; the most impactful trial was KATHERINE, which revealed a 11.3% absolute iDFS improvement with T-DM1 (compared to trastuzumab) in HER2-positive breast cancer patients who presented invasive residual disease following neoadjuvant treatment. These results, if reinforced by a subsequent overall survival benefit, will consolidate neoadjuvant treatment as the standard-of-care for most HER2-positive breast cancer patients. The addition of pertuzumab to adjuvant trastuzumab (APHINITY) or extending anti-HER2 therapy with 1 year of neratinib (ExteNET) also improved outcomes, but in a more modest way. In triple-negative early breast cancer patients presenting invasive residual disease after neoadjuvant chemotherapy, the CREATE-X trial demonstrated the benefit of post-neoadjuvant capecitabine. In patients with luminal tumours, updated results of the SOFT/TEXT trials confirmed the benefit of aromatase inhibitors plus ovarian suppression in high-risk premenopausal patients, and the 12-year results of the BIG1–98 trial demonstrated a sustained trend in favour of letrozole compared to tamoxifen in the adjuvant treatment of postmenopausal patients. The TAILOR-X study showed that, overall, patients with an intermediate recurrence risk score (11–25) in the OncotypeDX 21-gene assay did not benefit from adjuvant chemotherapy. A meta-analysis performed by the EBCTCG demonstrated that extended adjuvant aromatase inhibitors modestly reduced breast cancer recurrence risks, with a more pronounced benefit in patients previously treated with tamoxifen. Finally, an EBCTCG meta-analysis including patients with all breast cancer subtypes showed that dose-dense chemotherapy improved survival when compared to conventionally-timed chemotherapy.

New developments in the perioperative treatment of melanomas with locoregional advancement

Surgical intervention is the treatment of choice for patients with melanomas. However, the prognoses of the patients with melanomas at the IIC–IV stage, even after a complete resection of the lesions, is very diverse and, to a great degree, connected with a high risk of disease recurrence. The positive results of the studies in this area have resulted in systemic adjuvant therapy becoming the standard for patients in this group. New methods of systemic treatment – both the mo­lecularly targeted treatment with BRAF and MEK inhibitors (dabrafenib with trametinib) and anti-PD-1 immunotherapy (nivolumab or pembrolizumab) – are already registered in the United States and the European Union. Also the results of the studies concerning the use of preoperative systemic treatment in patients with loco-regionally advanced melanomas seem to be very promising.