scholarly journals Metastatic Uveal Melanoma: Treatment Strategies and Survival—Results from the Dutch Melanoma Treatment Registry

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1007 ◽  
Author(s):  
Anouk Jochems ◽  
Monique K. van der Kooij ◽  
Marta Fiocco ◽  
Maartje G. Schouwenburg ◽  
Maureen J. Aarts ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Uveal Melanoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Real Life ◽  
Treatment Strategies ◽  
Stage Iv ◽  
Lactate Dehydrogenase Level ◽  
Stage Iv Disease ◽  
Melanoma Treatment

Uveal melanoma (UM) is the most common primary intraocular tumor in adults. Up to 50% of UM patients will develop metastases. We present data of 175 metastatic UM patients diagnosed in the Netherlands between July 2012 and March 2018. In our cohort, elevated lactate dehydrogenase level (LDH) is an important factor associated with poorer survival (Hazard Ratio (HR) 9.0, 95% Confidence Interval (CI) 5.63–14.35), and the presence of liver metastases is negatively associated with survival (HR 2.09, 95%CI 1.07–4.08). We used data from the nation-wide Dutch Melanoma Treatment Registry (DMTR) providing a complete overview of the location of metastases at time of stage IV disease. In 154 (88%) patients, the liver was affected, and only 3 patients were reported to have brain metastases. In 63 (36%) patients, mutation analysis was performed, showing a GNA11 mutation in 28.6% and a GNAQ mutation in 49.2% of the analyzed patients. In the absence of standard care of treatment options, metastatic UM patients are often directed to clinical trials. Patients participating in clinical trials are often subject to selection and usually do not represent the entire metastatic UM population. By using our nation-wide cohort, we are able to describe real-life treatment choices made in metastatic UM patients and 1-year survival rates in selected groups of patients.

scholarly journals Molecular Insights and Emerging Strategies for Treatment of Metastatic Uveal Melanoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2761
Author(s):  
Fabiana Mallone ◽  
Marta Sacchetti ◽  
Alessandro Lambiase ◽  
Antonietta Moramarco
Keyword(s):  
Clinical Trials ◽  
Uveal Melanoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Metastatic Tumor ◽  
Clinical Use ◽  
Future Perspectives ◽  
Diagnosis And Prognosis ◽  
Novel Treatment ◽  
Combinational Therapies

Uveal melanoma (UM) is the most common intraocular cancer. In recent decades, major advances have been achieved in the diagnosis and prognosis of UM allowing for tailored treatments. However, nearly 50% of patients still develop metastatic disease with survival rates of less than 1 year. There is currently no standard of adjuvant and metastatic treatment in UM, and available therapies are ineffective resulting from cutaneous melanoma protocols. Advances and novel treatment options including liver-directed therapies, immunotherapy, and targeted-therapy have been investigated in UM-dedicated clinical trials on single compounds or combinational therapies, with promising results. Therapies aimed at prolonging or targeting metastatic tumor dormancy provided encouraging results in other cancers, and need to be explored in UM. In this review, the latest progress in the diagnosis, prognosis, and treatment of UM in adjuvant and metastatic settings are discussed. In addition, novel insights into tumor genetics, biology and immunology, and the mechanisms underlying metastatic dormancy are discussed. As evident from the numerous studies discussed in this review, the increasing knowledge of this disease and the promising results from testing of novel individualized therapies could offer future perspectives for translating in clinical use.

scholarly journals Hitting the Bull’s-Eye: Mesothelin’s Role as a Biomarker and Therapeutic Target for Malignant Pleural Mesothelioma

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3932
Author(s):  
Dannel Yeo ◽  
Laura Castelletti ◽  
Nico van Zandwijk ◽  
John E. J. Rasko
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Treatment Options ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Pleural Mesothelioma ◽  
Normal Tissues ◽  
Drug Conjugates ◽  
Aggressive Cancer ◽  
Immunotherapy Target ◽  
Bull's Eye

Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited treatment options and poor prognosis. MPM originates from the mesothelial lining of the pleura. Mesothelin (MSLN) is a glycoprotein expressed at low levels in normal tissues and at high levels in MPM. Many other solid cancers overexpress MSLN, and this is associated with worse survival rates. However, this association has not been found in MPM, and the exact biological role of MSLN in MPM requires further exploration. Here, we discuss the current research on the diagnostic and prognostic value of MSLN in MPM patients. Furthermore, MSLN has become an attractive immunotherapy target in MPM, where better treatment strategies are urgently needed. Several MSLN-targeted monoclonal antibodies, antibody–drug conjugates, immunotoxins, cancer vaccines, and cellular therapies have been tested in the clinical setting. The biological rationale underpinning MSLN-targeted immunotherapies and their potential to improve MPM patient outcomes are reviewed.

Management of Malignant Melanoma: Best Practices

2009 ◽  
Vol 13 (2) ◽  
pp. 55-73 ◽  
Author(s):  
Michael Smylie ◽  
Joël Claveau ◽  
Kenneth Alanen ◽  
Raymond Taillefer ◽  
Ralph George ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Best Practices ◽  
Gamma Probe ◽  
Treatment Options ◽  
Stage Iv ◽  
Primary Diagnosis ◽  
Interferon Α ◽  
Node Biopsy ◽  
Stage Iv Disease ◽  
Intraoperative Gamma Probe

Background: Melanoma is a commonly occurring cancer in Canada, with an estimated age-standardized incidence of 10 to 13 per 100,000. An estimated 4,300 new cases were diagnosed, and there were 880 reported deaths in 2005. Objective and Conclusion: The Canadian Expert Panel on Malignant Melanoma has developed best practices to improve the management of malignant melanoma. Sections include recommendations on primary diagnosis, dermatopathologic assessment, and reporting; use of preoperative lymphoscintigraphy and an intraoperative gamma probe to map and biopsy the sentinel lymph node; indications for surgical resection, sentinel node biopsy, and surgery for advanced disease; use of interferon-α adjuvant therapy and treatment options for stage IV disease; and management of central nervous system metastases.

scholarly journals Spermatic Cord Lymphoma: A Case Report and Literature Review

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Satoru Taguchi ◽  
Sayuri Takahashi ◽  
Katsuyuki Iida ◽  
Takashi Mizutani ◽  
Kazumi Yamaguchi ◽  
...  
Keyword(s):  
Spermatic Cord ◽  
Poor Prognosis ◽  
Early Stage ◽  
Treatment Options ◽  
Multidisciplinary Treatment ◽  
Stage Iv ◽  
Recommended Treatment ◽  
Testicular Lymphoma ◽  
Stage Iv Disease ◽  
Primary Testicular Lymphoma

Spermatic cord lymphoma is a rare lethal disease. It has a poor prognosis even in stage I or II disease when treated locally, therefore, multidisciplinary treatment for early stage is recommended. On the other hand, the treatment of choice for stage III or IV spermatic cord lymphoma remains to be determined. It is said that spermatic cord lymphoma is clinicopathologically similar to primary testicular lymphoma, therefore the treatment of spermatic cord lymphoma has often been determined by reference to the recommended treatment for primary testicular lymphoma. Here we report a new case of spermatic cord lymphoma, which was found in stage IV disease. We also review thirty-three cases which have been reported as spermatic cord lymphoma to date, and discuss treatment options.

Modern Clinician-initiated Clinical Trials to Determine Optimal Therapy for Multidrug-resistant Gram-negative Infections

2019 ◽  
Vol 71 (2) ◽  
pp. 433-439
Author(s):  
Adam G Stewart ◽  
Patrick N A Harris ◽  
Mark Chatfield ◽  
Scott R Evans ◽  
David van Duin ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Multidrug Resistant ◽  
Small Sample ◽  
Consensus Approach ◽  
Gram Negative ◽  
Therapeutic Trials ◽  
Clinical Trial Designs ◽  
Small Sample Sizes

Abstract Treatment options for multidrug-resistant (MDR) gram-negative infection are growing. However, postregistration, pragmatic, and clinician-led clinical trials in this field are few, recruit small sample sizes, and experience deficiencies in design and operations. MDR gram-negative therapeutic trials are often inefficient, only evaluating a single antibiotic or strategy at a time. Novel clinical trial designs offer potential solutions by attempting to obtain clinically meaningful conclusions at the end or during a trial, for many treatment strategies, simultaneously. An integrated, consensus approach to MDR gram-negative infection trial design is crucial.

Impact of treatment strategies on local control and survival in uterine carcinosarcomas.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16526-e16526
Author(s):  
Selim Yalcin ◽  
Omer Dizdar ◽  
Nadire Kucukoztas ◽  
Samed Rahatli ◽  
Ozlem Ozen ◽  
...  
Keyword(s):  
Uterine Cancer ◽  
Treatment Strategies ◽  
Stage Iv ◽  
Total Abdominal Hysterectomy ◽  
Abdominal Hysterectomy ◽  
Uterine Carcinosarcoma ◽  
Treatment Regimens ◽  
Stage Iv Disease ◽  
Standardized Treatment

e16526 Background: Carcinosarcoma is a biphasic neoplasm composed of a mixture of malignant epithelial and mesenchymal components. Uterine carcinosarcomas comprise only 3% of all uterine malignancies, however they account for a disproportionally higher rate of mortality from uterine cancer because of their agressive nature. No standardized treatment has yet been established. The purpose of this study was to determine the clinical characteristics, patterns of recurrence and survival outcomes in patients with uterine carcinosarcoma treated in our institution. Methods: Records of the patients with uterine carcinosarcoma were retrospectively evaluated and 29 pts with carcinosarcoma diagnosed between 2007 and 2012 were identified. All patients were initially treated surgically by the same surgeon with comprehensive staging, i.e. total abdominal hysterectomy, bilateral salphingooopherectomy , bilateral pelvic and paraaortic lymph node dissection and omentectomy. Demographic features, tumor characteristics, treatment regimens and patient outcomes in terms of relapse-free survival (RFS) and overall survival (OS) were analyzed. Results: Median age was 63 (range 43-78). 13 patients (45%) had stage I disease, 5 patients (17%) had stage III and 11 patients (38%) had stage IV disease at diagnosis. Median tumor size was 6 cm (range 1.7-20 cm) and lymphovascular invasion was present in 17 patients 59%). Twenty patients (69%) received chemotherapy (90% with paclitaxel and carboplatin) for 6 cycles. One patient received radiotherapy. Median follow up was 13 mos. Seventeen patients (59%) relapsed and 20 patients (69%) died on follow up. Two patients had vaginal cuff recurrence, 4 had pelvic, 4 had abdominal and 7 had distant recurrences. All recurrences were fatal. 3 year RFS was 31%. 3 year OS was 15%. Conclusions: Our data show that uterine carcinosarcomas tend to be more at more advanced stage at diagnosis and despite the use of chemotherapy and radiotherapy, overall prognosis is poor. Surgery remains the mainstay of treatment. More effective adjuvant strategies are needed to reduce relapse and death rates because recurrences are generally fatal.

NRG1 fusion-positive lung cancers: Clinicopathologic profile and treatment outcomes from a global multicenter registry.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9081-9081 ◽  
Author(s):  
Michaël Duruisseaux ◽  
Stephen V. Liu ◽  
Ji-Youn Han ◽  
Valerie Gounant ◽  
Jin-Yuan Shih ◽  
...  
Keyword(s):  
Single Agent ◽  
Treatment Strategies ◽  
Stage Iv ◽  
Large Cell ◽  
Disease Stage ◽  
Lung Cancers ◽  
Best Response ◽  
Pathologic Features ◽  
Platinum Based Chemotherapy ◽  
Stage Iv Disease

9081 Background: NRG1 fusions are potentially actionable driver events enriched in NSCLCs, particularly invasive mucinous adenocarcinomas (IMAs). These fusions activate HER3/HER2, supporting the therapeutic use of HER3 and/or HER2 inhibitors, but optimal treatment strategies remain unclear. Methods: A global, multicenter network of thoracic oncologists (6 countries, 13 institutions) identified patients with pathologically confirmed NRG1 fusion-positive NSCLCs. Anonymized clinical/pathologic features and clinical outcomes were collected retrospectively. Best response to systemic therapy was determined (RECIST v1.1). PFS was calculated (Kaplan-Meier). Results: 80 NRG1 fusion-positive NSCLCs were identified. RNA-based sequencing identified 66% (n = 53/80), DNA-based sequencing 18% (n = 14/80), and FISH 16% (n = 13/80) of cases. The most common upstream partners were CD74 (45%), SLC3A2 (31%), and SDC (9%). Most patients were female (64%) and never smokers (58%). Histology was adenocarcinoma in 95% (IMA, 91%), squamous 4%, large cell neuroendocrine 1%. At diagnosis, most patients had non-metastatic disease (stage: I 33%, II 27%, III 18%, IV 22%). The lifetime frequency of brain metastases was 15%. 12 patients received the HER2 inhibitor afatinib for stage IV disease. PD was the best response in 55% (n = 6/11) of evaluable patients with 18% PR (n = 2/11) and SD 18% (n = 2/11); median PFS was 3.5 months (range 0.6-16.5 months). 19 patients received platinum-based chemotherapy; most patients had SD as their best response (47%, n = 8); PD 41% (n = 7), PR 12% (n = 2). PD-L1 was negative in the majority of tumors (79%, n = 26/33) and none had high PD-L1 expression (range 0-20%). No responses to single-agent anti-PD-1/L1 therapy were observed (PD n = 5/6, SD n = 1/6: nivolumab/atezolizumab). No responses to chemoimmunotherapy (carboplatin, pemetrexed, pembrolizumab) were observed (SD n = 4/5, PD n = 1/5). Conclusions: RNA-based testing is an important component of NRG1 fusion detection. Novel targeted therapeutic approaches are needed as overall outcomes with afatinib are poor. NRG1 fusion-positive NSCLCs do not highly express PD-L1 and outcomes with immunotherapy ± chemotherapy are poor.

scholarly journals Contemporary outcomes from the use of regular imaging to detect relapse in high-risk cutaneous melanoma

ESMO Open ◽  
2018 ◽  
Vol 3 (2) ◽  
pp. e000317 ◽  
Author(s):  
Kok Haw Jonathan Lim ◽  
Lavinia Spain ◽  
Claire Barker ◽  
Alexandros Georgiou ◽  
Gerard Walls ◽  
...  
Keyword(s):  
High Risk ◽  
Systemic Therapy ◽  
Cutaneous Melanoma ◽  
Treatment Options ◽  
Stage Iv ◽  
Time To Recurrence ◽  
Positron Emission ◽  
Risk Melanoma ◽  
Stage Iv Disease

BackgroundAgreement on the utility of imaging follow-up in patients with high-risk melanoma is lacking. A UK consensus statement recommends a surveillance schedule of CT or positron-emission tomography-CT and MRI brain (every 6 months for 3 years, then annually in years 4 and 5) as well as clinical examination for high-risk resected Stages II and III cutaneous melanoma. Our aim was to assess patterns of relapse and whether imaging surveillance could be of clinical benefit.Patients and methodsA retrospective study of patients enrolled between July 2013 and June 2015 from three UK tertiary cancer centres followed-up according to this protocol was undertaken. We evaluated time-to-recurrence (TTR), recurrence-free survival (RFS), method of detection and characteristics of recurrence, treatment received and overall survival (OS).ResultsA total of 173 patients were included. Most (79%) had treated Stages IIIB and IIIC disease. With a median follow-up of 23.3 months, 82 patients (47%) had relapsed. Median TTR was 10.1 months and median RFS was 21.2 months. The majority of recurrences (66%) were asymptomatic and detected by scheduled surveillance scan. Fifty-six (68%) patients recurred with Stage IV disease, with a median OS of 25.3 months; 26 (31.7%) patients had a locoregional recurrence, median OS not reached (P=0.016). Patients who underwent surgery at recurrence for either Stage III (27%) or IV (18%) disease did not reach their median OS. The median OS for the 33 patients (40%) who received systemic therapy was 12.9 months.ConclusionImaging appears to reliably detect subclinical disease and identify patients suitable for surgery, conferring favourable outcomes. The short median TTR provides rationale to intensify imaging schedule in the first year of surveillance. The poor OS of patients treated with systemic therapy probably reflects the relatively inferior treatment options during this time and requires further evaluation in the current era.

scholarly journals New Perspectives for Eye-Sparing Treatment Strategies in Primary Uveal Melanoma

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 134
Author(s):  
Krzysztof Bilmin ◽  
Kamil J. Synoradzki ◽  
Anna M. Czarnecka ◽  
Mateusz J. Spałek ◽  
Tamara Kujawska ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Uveal Melanoma ◽  
Focused Ultrasound ◽  
Early Stage ◽  
Treatment Options ◽  
Treatment Strategies ◽  
High Intensity Focused Ultrasound ◽  
Local Concentration ◽  
Proton Beam Radiotherapy ◽  
Stage Of Development

Uveal melanoma is the most common intraocular malignancy and arises from melanocytes in the choroid, ciliary body, or iris. The current eye-sparing treatment options include surgical treatment, plaque brachytherapy, proton beam radiotherapy, stereotactic photon radiotherapy, or photodynamic therapy. However, the efficacy of these methods is still unsatisfactory. This article reviews several possible new treatment options and their potential advantages in treating localized uveal melanoma. These methods may be based on the physical destruction of the cancerous cells by applying ultrasounds. Two examples of such an approach are High-Intensity Focused Ultrasound (HIFU)—a promising technology of thermal destruction of solid tumors located deep under the skin and sonodynamic therapy (SDT) that induces reactive oxygen species. Another approach may be based on improving the penetration of anti-cancer agents into UM cells. The most promising technologies from this group are based on enhancing drug delivery by applying electric current. One such approach is called transcorneal iontophoresis and has already been shown to increase the local concentration of several different therapeutics. Another technique, electrically enhanced chemotherapy, may promote drug delivery from the intercellular space to cells. Finally, new advanced nanoparticles are developed to combine diagnostic imaging and therapy (i.e., theranostics). However, these methods are mostly at an early stage of development. More advanced and targeted preclinical studies and clinical trials would be needed to introduce some of these techniques to routine clinical practice.

scholarly journals The Emerging Role of c-Met in Carcinogenesis and Clinical Implications as a Possible Therapeutic Target

2022 ◽  
Vol 2022 ◽  
pp. 1-12
Author(s):  
Antonio Faiella ◽  
Ferdinando Riccardi ◽  
Giacomo Cartenì ◽  
Martina Chiurazzi ◽  
Livia Onofrio
Keyword(s):  
Clinical Trials ◽  
Epithelial Mesenchymal Transition ◽  
Target Therapy ◽  
Treatment Options ◽  
Survival Rates ◽  
Response To Treatment ◽  
Tyrosine Kinase Receptor ◽  
Mesenchymal Transition ◽  
Surface Receptors ◽  
Clinical Consequences

Background. c-MET is a receptor tyrosine kinase receptor (RTK) for the hepatocyte growth factor (HGF). The binding of HGF to c-MET regulates several cellular functions: differentiation, proliferation, epithelial cell motility, angiogenesis, and epithelial-mesenchymal transition (EMT). Moreover, it is known to be involved in carcinogenesis. Comprehension of HGF-c-MET signaling pathway might have important clinical consequences allowing to predict prognosis, response to treatment, and survival rates based on its expression and dysregulation. Discussion. c-MET represents a useful molecular target for novel engineered drugs. Several clinical trials are underway for various solid tumors and the development of new specific monoclonal antibodies depends on the recent knowledge about the definite c-MET role in each different malignance. Recent clinical trials based on c-MET molecular targets result in good safety profile and represent a promising therapeutic strategy for solid cancers, in monotherapy or in combination with other target drugs. Conclusion. The list of cell surface receptors crosslinking with the c-MET signaling is constantly growing, highlighting the importance of this pathway for personalized target therapy. Research on the combination of c-MET inhibitors with other drugs will hopefully lead to discovery of new effective treatment options.

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