scholarly journals New Therapeutic Perspectives in the Treatment of Uveal Melanoma: A Systematic Review

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1311
Author(s):  
Mario Damiano Toro ◽  
Lucia Gozzo ◽  
Luciano Tracia ◽  
Marco Cicciù ◽  
Filippo Drago ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Phase I ◽  
Uveal Melanoma ◽  
Metastatic Disease ◽  
Treatment Options ◽  
Therapeutic Options ◽  
Treatment Modalities ◽  
New Therapeutic Approaches ◽  
New Treatment

Uveal melanoma (UM) is a rare disease, but the most common primary intraocular cancer, mostly localized in the choroid. Currently, the first-line treatment options for UM are radiation therapy, resection, and enucleation. However, although these treatments could potentially be curative, half of all patients will develop metastatic disease, whose prognosis is still poor. Indeed, effective therapeutic options for patients with advanced or metastatic disease are still lacking. Recently, the development of new treatment modalities with a lower incidence of adverse events, a better disease control rate, and new therapeutic approaches, have merged as new potential and promising therapeutic strategies. Additionally, several clinical trials are ongoing to find new therapeutic options, mainly for those with metastatic disease. Many interventions are still in the preliminary phases of clinical development, being investigated in phase I trial or phase I/II. The success of these trials could be crucial for changing the prognosis of patients with advanced/metastatic UM. In this systematic review, we analyzed all emerging and available literature on the new perspectives in the treatment of UM and patient outcomes; furthermore, their current limitations and more common adverse events are summarized.

Treatment options for unstable ankle fractures in older adults: A systematic review and meta-analysis

Trauma ◽  
2020 ◽  
pp. 146040862093797
Author(s):  
Andrew Grazette ◽  
Catrin Wigley ◽  
Andrew Metcalfe
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Internal Fixation ◽  
Open Reduction ◽  
Meta Analysis ◽  
Treatment Options ◽  
Ankle Fractures ◽  
Treatment Modalities ◽  
Current Evidence ◽  
Treatment Groups

Background Ankle fractures are the third most common fracture in the elderly. Patients over 60 years are more severely affected by these injuries than their younger counterparts and have a higher rate of complications regardless of the management strategy. Traditional management strategies for unstable ankle fractures include plaster immobilisation and open reduction and internal fixation, with newer modalities such as intramedullary fixation becoming increasingly popular. The aim of this review is to establish the best current evidence for or against different treatment strategies. Methods A systematic review and meta-analysis of randomised controlled trials comparing treatment options for unstable ankle fractures in adults over 55 was conducted, with the primary outcome being functional assessment score at 6–12 months (Olerud and Molander Ankle Score). Secondary outcomes were adverse events including infection and re-operation. Results The search strategies identified 426 articles. After screening and full text review, four papers met the inclusion and exclusion criteria, providing data on 754 ankle fractures. Alternative treatment groups were tibio-talo-calcaneal nail, fibular nail and casting and were compared to open reduction and internal fixation. Meta-analysis of the data showed no difference in Olerud and Molander Ankle Score between treatment modalities at 6–12 months. There was, however, a significant reduction in the incidence of adverse events (OR 0.59 (0.44, 0.81)) and wound infection (0.13 (0.05, 0.31)) in the alternative treatment groups compared to open reduction and internal fixation. Conclusion The current evidence shows no significant difference between treatment modalities for ankle fractures in older adults in terms of functional outcome. Open reduction and internal fixation has a higher rate of adverse events and wound infection when compared to alternative treatments. Therefore, surgery should be carefully considered and if undertaken, in a select patient cohort other treatment modalities, such as intramedullary fixation should be considered.

scholarly journals Current Opinion and Knowledge on Peritoneal Carcinomatosis: A Survey among a Swiss Oncology Network

Chemotherapy ◽  
2018 ◽  
Vol 63 (3) ◽  
pp. 143-147 ◽  
Author(s):  
Fabian Grass ◽  
David Martin ◽  
Michael Montemurro ◽  
Patrice Mathevet ◽  
Anita Wolfer ◽  
...  
Keyword(s):  
Treatment Options ◽  
Treatment Strategies ◽  
Treatment Modalities ◽  
Therapeutic Approaches ◽  
Current Opinion ◽  
New Therapeutic Approaches ◽  
Case Vignettes ◽  
Colorectal Origin ◽  
New Treatment ◽  
Practice Knowledge

Aims of the Study: The present survey aimed to evaluate current opinion and practice regarding peritoneal metastasis (PM), satisfaction with available treatment options, and need for new therapeutic approaches. Methods: This was a qualitative study conducted between October 2016 and October 2017 in the Réseau Suisse Romand d’Oncologie including 101 members of various oncological specialties. Participants’ demographics, current practice, knowledge, and satisfaction regarding available treatment options and need for new treatment options were assessed by semantic differential scales through 33 closed questions with automatic reminders at 4-, 8-, 12-, and 16-week intervals. Results: Twenty-seven participants (27%) completed the survey. Participants were gastrointestinal or gynecologic oncologists and surgeons. Most participants (67%) evaluated their knowledge on PM as moderate, while 22% considered themselves as experts. Clinical usefulness of systemic chemotherapy and hyperthermic intraperitoneal chemotherapy was judged to be moderate to high for PM of ovarian and colorectal origin and moderate to poor for gastric origin. Satisfaction with available treatment options was 6/10 (interquartile range [IQR] 4–7) for ovarian, 5/10 (IQR 3–7) for colorectal, and 3/10 (IQR 1–3) for gastric PM. Treatment strategies varied widely for typical case vignettes. The need for new treatment modalities was rated as 8/10 (IQR 6–10). Conclusion: Usefulness of and satisfaction with available treatment options for PM were rated as moderate at best by oncological experts, and treatment strategies differed importantly among participants. There appears to be a clear need for standardization and new treatment modalities.

Management of thoracic aortic lesions - the future is endovascular

VASA ◽  
2012 ◽  
Vol 41 (3) ◽  
pp. 163-176 ◽  
Author(s):  
Weidenhagen ◽  
Bombien ◽  
Meimarakis ◽  
Geisler ◽  
A. Koeppel
Keyword(s):  
Thoracic Aorta ◽  
Clinical Decision Making ◽  
Treatment Options ◽  
Clinical Decision ◽  
Clinical Results ◽  
Treatment Modalities ◽  
Traumatic Rupture ◽  
Descending Thoracic Aorta ◽  
New Treatment ◽  
Aneurysm Dissection

Open surgical repair of lesions of the descending thoracic aorta, such as aneurysm, dissection and traumatic rupture, has been the “state-of-the-art” treatment for many decades. However, in specialized cardiovascular centers, thoracic endovascular aortic repair and hybrid aortic procedures have been implemented as novel treatment options. The current clinical results show that these procedures can be performed with low morbidity and mortality rates. However, due to a lack of randomized trials, the level of reliability of these new treatment modalities remains a matter of discussion. Clinical decision-making is generally based on the experience of the vascular center as well as on individual factors, such as life expectancy, comorbidity, aneurysm aetiology, aortic diameter and morphology. This article will review and discuss recent publications of open surgical, hybrid thoracic aortic (in case of aortic arch involvement) and endovascular repair in complex pathologies of the descending thoracic aorta.

New Therapeutics for Ulcerative Colitis

2021 ◽  
Vol 72 (1) ◽  
pp. 199-213
Author(s):  
Robert P. Hirten ◽  
Bruce E. Sands
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Disease ◽  
Clinical Remission ◽  
Treatment Options ◽  
Treatment Modalities ◽  
Therapeutic Approaches ◽  
Stages Of Development ◽  
The Future ◽  
New Treatment ◽  
Novel Therapeutic

Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease of the colon with a variable course. Despite advances in treatment, only approximately 40% of patients achieve clinical remission at the end of a year, prompting the exploration of new treatment modalities. This review explores novel therapeutic approaches to UC, including promising drugs in various stages of development, efforts to maximize the efficacy of currently available treatment options, and non-medication-based modalities. Treatment approaches which show promise in impacting the future of UC management are highlighted.

Novel treatment options in advanced adenoid cystic carcinoma of the breast.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13071-e13071
Author(s):  
Evan Wenig ◽  
Reumu E. Birhiray
Keyword(s):  
Disease Control ◽  
Adenoid Cystic Carcinoma ◽  
Metastatic Disease ◽  
Triple Negative ◽  
Treatment Options ◽  
Locally Advanced ◽  
Therapeutic Options ◽  
Breast Mass ◽  
Ongoing Research ◽  
Adenoid Cystic

e13071 Background: Adenoid cystic carcinoma (ACC) accounts for less than 0.1% of all breast cancer cases. The disease typically remains localized and indolent, and frequently occurs with triple negative status. Methods: In patients with locally advanced or metastatic disease, chemotherapy for triple negative breast carcinoma is seldom effective. Thus new treatment paradigms are desired. Drug targeted analysis derived from next generation sequencing and identification of driver mutations may offer a bright future in treatment options in chemo-resistant malignancy. Results: A 53 year old woman presented with breast mass and mastectomy with stage pT3N0M0 triple negative ACC of the breast resulting in observation. She later relapsed with chest wall disease, resulting in resection and radiation therapy. Shortly thereafter, she relapsed with pulmonary metastatic disease. She was treated with carboplatin and doxorubicin which were discontinued due to disease progression. Liquid assay revealed an IDH2 mutation, prompting treatment with enasidenib with ongoing evidence of disease control at 4 months. Patient tolerated treatment well without grade 3 or 4 adverse reactions. A 48 year old woman presented with an increasing 9.5 cm unresectable breast mass without distant metastasis. Pathology showed triple negative ACC of the breast, resulting in chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel with clinically progressive disease. She represented with necrotic and ulcerating changes of the breast. Foundational genomic testing showed an FGFR2 mutation. After four months of treatment with erdafitinib, she had resolution of pain and cessation of pain medication. Her therapy led to a grade 2 adverse event related to hyperphosphatemia. She underwent surgical resection with negative margins. Conclusions: These examples illustrate a potential treatment paradigm for a rare malignancy for which there is no standard of care. Here we present two desperate cases, one of which had a driver mutation of IDH2, and the other FGFR2 for which there are targeted therapies approved in other disease states. The use of these two agents resulted in clinical benefit. A patient with metastatic disease treated with enasidenib has ongoing disease control for over 4 months with minimal adverse reaction. A patient with advanced local disease requiring narcotics and gabapentin for pain control treated with erdafitinib had significant symptomatic control with successful cessation of pain medications and ability to undergo potentially curable mastectomy with negative margins despite progression on prior chemotherapy. In summary, ongoing research of ACC of the breast will be required. Alternative therapeutic options related to targeted treatment may offer promise to clinical outcomes in the future. For cases of locally advanced or metastatic disease, the use of targeted therapy may offer new therapeutic options.

Immunomodulation in Autoimmune Interstitial Lung Disease

Respiration ◽  
2020 ◽  
Vol 99 (10) ◽  
pp. 819-829
Author(s):  
Benjamin Seeliger ◽  
Antje Prasse
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Systemic Disease ◽  
Treatment Options ◽  
Interstitial Lung Diseases ◽  
Treatment Modalities ◽  
Established Disease ◽  
Synthetic Dmards ◽  
New Treatment ◽  
Underlying Diseases

Interstitial lung diseases (ILDs) associated with autoimmune or systemic disease are increasingly recognized and our pathophysiological understanding rapidly expanding. Treatment modalities, however, are still mainly driven by established disease-modifying antirheumatic drugs (DMARDs) where, despite decades of experience of their use in the underlying diseases such as rheumatoid arthritis, mostly ret­rospective data exist informing their effect on the course of interstitial lung disease (ILD). In recent years, randomized trials investigating the effects of biological DMARDs (bDMARDs) have been completed or are currently running, generating new treatment options for often relentlessly progressive diseases. Herein, we summarize the evidence and current use of both synthetic DMARDs and bDMARDs in the context of ILDs associated with autoimmune/systemic disease.

scholarly journals MLTI-14. A SYSTEMATIC REVIEW OF TREATMENT PARADIGMS FOR PATIENTS WITH BREAST CANCER AND ONE OR MORE BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i17-i17
Author(s):  
Yosef Ellenbogen ◽  
Karanbir Brar ◽  
Nebras Warsi ◽  
Jetan Badhiwala ◽  
Alireza Mansouri
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Adverse Events ◽  
Brain Metastases ◽  
Treatment Options ◽  
Inclusion Criteria ◽  
Open Label ◽  
Treatment Groups ◽  
Molecular Features ◽  
Significant Difference

Abstract BACKGROUND: Upwards of 50% of patients with advanced breast cancer are diagnosed with brain metastases (BM). Treatment options for these patients have been rapidly evolving due to increased understanding of the tumor pathophysiology and its genetic underpinnings. This systematic review of randomized controlled trials (RCTs) aims to clarify the evidence guiding the treatment of brain metastases from breast cancer. METHODS: MEDLINE, EMBASE, Cochrane Controlled Register of Trials, ClincialTrials.gov, and Web of Science were searched from inception to October 2018 for RCTs comparing treatments for breast cancer BM. We screened studies, extracted data, and assessed risk of bias independently and in duplicate. Outcomes assessed were overall survival (OS), progression-free survival (PFS), and adverse events (Grade 3+). RESULTS: Among 3188 abstracts, only 3 RCTs (N=412; mean sample size per group N=54.7) meeting inclusion criteria were identified. The studies were phase II or III open-label parallel superiority trials. Inclusion criteria among these trials consisted of age >18 with radiologic evidence of >1 BM. Exclusion criteria consisted of poor-performance functional status (ECOG >2 or KPS < 70). The treatment groups included whole-brain radiation therapy (WBRT) vs WBRT + Temozolomide, WBRT vs WBRT + Efaproxiral, and Afatinib vs Vinorelbine vs investigators’ choice (86% of these patients received WBRT or SRS prior to study enrolment). While two trials found no significant difference in OS, one trial found significant improvement in OS with Efaproxiral in addition to WBRT compared to WBRT alone (HR 0.52; 95%CI 0.332–0.816). No significant differences were found with PFS or rate of adverse events amongst treatment groups. CONCLUSION: Considering the high prevalence of breast cancer BM and our improved understanding of genomic/molecular features of these tumors, a greater number of RCTs dedicated at this disease are needed.

Metastatic feline mammary cancer: prognostic factors, outcome and comparison of different treatment modalities – a retrospective multicentre study

2020 ◽  
pp. 1098612X2096441
Author(s):  
Gonçalo Petrucci ◽  
Joaquim Henriques ◽  
Hugo Gregório ◽  
Gonçalo Vicente ◽  
Justina Prada ◽  
...  
Keyword(s):  
Metastatic Disease ◽  
Adjuvant Treatment ◽  
Imaging Techniques ◽  
Treatment Options ◽  
Clinical Signs ◽  
Stage Iv ◽  
Metronomic Chemotherapy ◽  
Maximum Tolerated Dose ◽  
Treatment Modalities ◽  
Number Of Patients

Objectives Although feline mammary carcinomas (FMCs) are highly metastatic, the literature and treatment options pertaining to advanced tumours are scarce. This study aimed to investigate the clinical outcome of metastatic FMC with or without adjuvant treatment. Methods The medical records of 73 cats with metastatic FMC (stage 4) were reviewed and included in this study. Metastatic disease was detected by distinct imaging techniques (radiography, ultrasound and CT) and confirmed by cytology and/or histopathology. Cats with adjuvant chemotherapy treatment (n = 34) were divided into three groups: group 1 (n = 9) cats receiving maximum tolerated dose chemotherapy; group 2 (n = 15) cats receiving metronomic chemotherapy; and group 3 (n = 10) cats treated with toceranib phosphate. The study endpoints were time to progression (TTP) and tumour-specific survival (TSS). Treatment-related toxicity was evaluated according to the Veterinary Co-operative Oncology Group’s Common Terminology Criteria for Adverse Events version 1.1 (VCOG-CTCAE). Results Overall mean TTP and TSS were 23 and 44 days, respectively. Cats with clinical signs at the time of diagnosis had a lower TSS (14 days) than asymptomatic cats (120 days; P <0.001). Cats with pleural effusion had a lower TSS (16 days) than cats without ( P <0.001). Median TSS was 58, 75 and 63 in groups 1, 2 and 3, respectively ( P = 0.197). Toxicity was observed in 66.7%, 20% and 30% of cats in groups 1, 2 and 3, respectively. Conclusions and relevance To the best of our knowledge, this study includes the highest number of patients with metastatic FMC assessed. Despite the overall poor prognosis, some cats survived >6 months, indicating that adjuvant treatment may be an option to consider in metastatic disease. More studies are warranted for better understanding and management of stage IV patients.

scholarly journals Molecular basis of ALS and FTD: implications for translational studies / Molekularna osnova ALS-a i FTD-a: implikacije za translacijska istraživanja

2015 ◽  
Vol 66 (4) ◽  
pp. 285-290 ◽  
Author(s):  
Rajka M. Liščić
Keyword(s):  
Molecular Mechanisms ◽  
Treatment Options ◽  
Clinical Genetic ◽  
Ubiquitinated Proteins ◽  
New Therapeutic Approaches ◽  
Hexanucleotide Repeat ◽  
Repeat Expansions ◽  
C9orf72 Gene ◽  
New Treatment ◽  
Mutant Genes

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders, related by signs of deteriorating motor and cognitive functions, and short survival. The cause is unknown and no effective treatment currently exists. For ALS, there is only a drug Riluzole and a promising substance arimoclomol. The overlap between ALS and FTD occurs at clinical, genetic, and pathological levels. The majority of ALS cases are sporadic (SALS) and a subset of patients has an inherited form of the disease, familial ALS (FALS), with a common SOD1 mutation, also present in SALS. A few of the mutant genes identified in FALS have also been found in SALS. Recently, hexanucleotide repeat expansions in C9ORF72 gene were found to comprise the largest fraction of ALS- and FTD-causing mutations known to date. TAR DNA-binding protein 43 (TDP-43), encoded by the TARDBP gene, has been identified as the pathological protein of FALS, SALS and, less frequently, FTD. The less frequent TDP-43 pathology in other forms of familial FTD has been linked to a range of mutations in GRN, FUS/TLS, rarely VCP, and other genes. TDP-43 and FUS/TLS have striking structural and functional similarities, most likely implicating altered RNA processing as a major event in ALS pathogenesis. The clinical overlap of the symptoms of FTD and ALS is complemented by overlapping neuropathology, with intracellular inclusions composed of microtubule-associated protein tau, TDP-43 and less frequently FUS, or unknown ubiquitinated proteins. Furthermore, new therapeutic approaches continue to emerge, by targeting SOD1, TDP-43 or GRN proteins. This review addresses new advances that are being made in our understanding of the molecular mechanisms of both diseases, which may eventually translate into new treatment options.

scholarly journals Efficacy and Safety of Histone Deacetylase Inhibitors in Multiple Myeloma - a Systematic Review of Early Phase Clinical Trials

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5629-5629
Author(s):  
Sharoon Samuel ◽  
Muhammad Junaid Tariq ◽  
Muhammad Usman ◽  
Amna Khalid ◽  
Muhammad Asad Fraz ◽  
...  
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Adverse Events ◽  
Phase I ◽  
Hdac Inhibitors ◽  
Complete Response ◽  
Number Of Patients ◽  
Grade 3 ◽  
Early Phase Clinical Trials

Abstract Introduction Recent studies in novel therapies have created opportunities for new treatment regimens to be used in the management of multiple myeloma. Histone deacetylase (HDAC) inhibitors lead to epigenetic manipulation of multiple myeloma (MM) cells by reducing resistance to pro-apoptotic signals. Panobinostat is an FDA approved HDAC inhibitor for multiple myeloma. The aim of this article is to study the safety, efficacy and dose limiting toxicities of HDAC inhibitors in the early phase clinical trials in multiple myeloma. Methods We performed a comprehensive literature search for phase I & I/II trials of HDAC inhibitors during last ten years using following databases: PubMed, Embase, AdisInsight, and Clinicaltrials.gov. Studies involving HDAC inhibitors in multiple myeloma other than panobinostat irrespective of the age, sex or specific eligibility criteria were included. Results Out of 2537 studies, we included 25 trials (23 phase I, 2 phase I/II) of HDAC inhibitors in this systematic review having a total of 518 patients. Of these, 471(90.9%) patients were evaluable for response. Vorinostat (Vor) is the most studied drug used in 13 trials (n=281). Two trials had Vor-only regimen and the remaining 11 had combination regimens mostly with lenalidomide and bortezomib. Vor, in combination with lenalidomide (R), bortezomib (V) and dexamethasone (d) has showed 100% overall response rate (ORR) in 30 newly diagnosed multiple myeloma (NDMM) patients, (Kaufmann et al., 2016), fifty two percent patients achieved very good partial response (VGPR) and 28% patients showed complete response (CR). Another study using Vor + R regimen after autologous stem cell transplant in 16 NDMM patients showed VGPR in 7, stringent complete response (sCR) in 4, partial response (PR) in 2 and CR in 3 patients (Sborov et al.). Grade 3 neutropenia was seen in 1 patient in this study. Richter et al, 2011 showed an ORR of 24% in 29 relapsed refractory multiple myeloma (RRMM) patients with Vor only regimen. Another study (Kaufmann et al., 2012) with Vor only regimen used in 10 RRMM patients showed stable disease (SD) in 9 and minimal response (MR) in 1 patient. ORR of 65% was achieved in 31 RRMM patients receiving Vor in combination with doxorubicin & bortezomib (Vorhees et al, 2017). Thrombocytopenia & neutropenia were reported in 94% and 59% patients respectively. Ricolinostat in combination with Rd and Vd achieved an ORR of 55% and 29% respectively in two studies with 38 and 57 evaluable patients (NCT01583283, NCT01323751). Another ricolinostat regimen with pomalidomide & dexamethasone achieved ≥PR in 6/11 RRMM patients (Madan et al., 2016). Table 1 illustrates the efficacy, number of patients and regimens used in all the studies in this systematic review. Quisinostat in a 2017 study by Moreau P et al. (NCT01464112) showed an ORR of 88% in a combination regimen with Vd in RRMM patients (N=18). Drug related adverse events were seen in 13 patients, thrombocytopenia being most common in 11 patients, 2 patients had grade 3 cardiac disorders and 1 patient had a cardiac arrest. Romidepsin in a phase I/II study (Harrison et al., 2011) combined with Vd was used in 25 RRMM patients. ORR was 60% with VGPR n=7, CR n=2, PR n=6, SD n=5 and PD n=1. Grade ≥3 thrombocytopenia in 16, neutropenia in 9 and peripheral neuropathy in 2 patients was seen. Popat et al used combination of two HDAC inhibitors CHR 3996 and tosedostat in 20 RRMM patients. ORR was 10% and SD was seen in 30% patients. Grade 3/4 toxicities seen were thrombocytopenia (n=12), leukopenia (n=6) and diarrhea (n=5). A phase I study on AR-42 drug in 17 RRMM patients (Sborov et al., 2017) showed SD in 10, PD in 4, MR in 3 patients with progression free survival (PFS) of 8.2 months. Thrombocytopenia, neutropenia and lymphopenia were seen in 11, 10 and 6 patients respectively. A detail of all grade 3 and higher adverse events along with dose limiting toxicity is given in table 2. Three trials (NCT02576496, NCT01947140, NCT03051841) of Edo-S101, romidepsin and CKD-581 are currently recruiting with 84, 93 and 18 planned number of patients. Conclusion Regimens containing vorinostat have shown an ORR up to 100% in NDMM patients. HDAC inhibitors have also shown promising efficacy up to 88% ORR in RRMM population. Majority of the patients developed cytopenias as hematological adverse events. Disclosures No relevant conflicts of interest to declare.

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