Predictive and Prognostic Factors in Melanoma Central Nervous System Metastases-A Cohort Study.

BACKGROUND: Melanoma is the cancer with the highest risk of dissemination to the central nervous system (CNS), one of the leading causes of mortality from this cancer. OBJECTIVE: To identify patients at higher risk of developing CNS metastases and to evaluate associated prognostic factors. METHODS: A cohort study (1998-2023) assessed patients who developed CNS melanoma metastases. Multivariate logistic regression was used to identify predictive factors at melanoma diagnosis for CNS metastasis. Cox regression analysis evaluated the CNS-independent metastasis-related variables impacting survival. RESULTS: Out of 4718 patients, 380 (8.05%) developed CNS metastases. Multivariate logistic regression showed that a higher Breslow index, mitotic rate ≥ 1 mm2, ulceration, and microscopic satellitosis were significant risk factors for CNS metastasis development. Higher patient age and the location of the primary tumor in the upper or lower extremities were protective factors. In survival analysis, post-CNS metastasis, symptomatic disease, prior non-CNS metastases, CNS debut with multiple metastases, elevated LDH levels, and leptomeningeal involvement correlated with poorer survival. CONCLUSION: Predictive factors in the primary tumor independently associated with brain metastases include microscopic satellitosis, ulceration, higher Breslow index, and trunk location. Prognostic factors for lower survival in CNS disease include symptomatic disease, multiple CNS metastases, and previous metastases from different sites.

Prolonged Responses With Trastuzumab Emtasine Treatment of Human Epidermal Growth Factor Receptor 2-positive Metastatic Breast Cancer Refractory to Trastuzumab and Pertuzumab: Systematic Review of Evidence.

Amplification of human epidermal growth factor receptor 2 (HER2) occurs in around 25% of breast cancers and has been associated with aggressive disease. Here, we summarize published evidence on efficacy and prolonged responses with trastuzumab emtansine (T-DM1) after first-line trastuzumab plus pertuzumab and provide possible factors related to prolonged responses to T-DM1. We conducted a literature search using PubMed, and articles that were published in English between July 1, 2012 and December 31, 2019 were included. A review of the bibliography included in the articles found was made. Nine articles were eligible; 2 were case reports, and the remaining 7 were nonexperimental studies, all retrospective. Five were multi-center works. The total number of patients was 796 (276 received pertuzumab). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used for this systematic review. The population included was heterogeneous among studies according to hormone receptor status, de novo metastatic disease, number of metastatic sites, visceral involvement, brain metastasis, previous neoadjuvant or adjuvant trastuzumab, and line of therapy in which T-DM1 was administered. Less efficacy in terms of responses (overall response rate, 18%-33%) and progression-free survival (4-6 months) with second-line T-DM1, in patients pretreated with pertuzumab, was shown (if compared with the EMILIA trial). The results are more similar to those of the TH3RESA trial (very pretreated population). Prolonged treatments (6 months or more) were observed in at least 17% of cases. The efficacy of T-DM1 after a previous pertuzumab treatment is lower than if pertuzumab is not given, although prolonged responses are observed in this setting.

Albumin-bound paclitaxel as new treatment for metastatic cholangiocarcinoma: A case report.

BACKGROUND: Cholangiocarcinomas are rare and very aggressive tumors. Most patients have advanced-stage or unresectable disease at presentation, and the systemic therapies have limited efficacy. Albumin-bound paclitaxel (nab-paclitaxel) is a solvent-free taxane that has been approved for the treatment of some cancers such as breast, non-small cell lung and pancreatic cancer, however it has not been applied to treat cholangiocarcinoma. We have both preclinical and clinical evidence of the efficacy of nab-paclitaxel in cholangiocarcinoma, yet no phase 3 trials have been made. CASE SUMMARY: A 63-year-old man was diagnosed in December 2016 with stage III B intrahepatic cholangiocarcinoma. Surgery was performed, followed by adjuvant chemotherapy treatment with capecitabine and gemcitabine; although, the gemcitabine was suspended due to allergic reaction after two cycles. In April 2019, metastatic cholangiocarcinoma relapse was diagnosed, and a first-line treatment with FOLFOX scheme was started. Eight cycles were administered, producing an initial clinical improvement and decrease in blood tumor marker levels. Radiological and serological progression was noted in September 2019. As a second-line treatment, FOLFIRI was not recommended due to risk of worsening the patient's tumor-related diarrhea. A combination therapy with gemcitabine was not feasible, as the patient had previously suffered from an allergic reaction to this treatment. We decided to use nab-paclitaxel as a second-line treatment, and four cycles were administered. Both clinical and serological responses were observed, and a radiological mixed response was also noted. CONCLUSION: Advanced cholangiocarcinoma could be treated with nab-paclitaxel monotherapy, which should be studied in combination with other types of treatment (chemotherapy, fibroblast growth factor receptor inhibitors).

Myocarditis and carotidynia caused by Granulocyte-Colony stimulating factor administration.

A 59 year-old woman was treated with adjuvant chemotherapy for triple negative breast cancer (TNBC) stage IB. She received pegfilgrastrim as secondary prophylaxis of neutropenia. After administration of pegfilgrastrim on day 11, she was hospitalised because of carotidynia and myocarditis that improved with antibiotics and steroids as an infection was suspected. Once she was recovered, another cycle of chemotherapy with pegfilgrastrim was administrated. At this time, the patient presented to our hospital with fever, odynophagia and chest pain, with diagnosis of myocarditis coupled with cardiogenic shock. She received antibiotics and steroids, advanced life support and also a pericardial window was done, with recovery of her condition. After a complete evaluation and exclusion of other possible aetiologies, we concluded that pegfilgrastrim was responsible for inducing carotidynia and myocarditis. Few cases have been published about Granulocyte-Colony stimulating factor (G-CSF) induced carotidynia and aortitis. However, this is the first reported case about G-CSF induced myocarditis and carotidynia.

Cardiac toxicity of immune-checkpoint inhibitors: a clinical case of nivolumab-induced myocarditis and review of the evidence and new challenges.

Immune checkpoint inhibitors have revolutionized cancer treatment due to their undeniable efficacy, but a range of new adverse events (AE) has emerged. In particular, cardiac toxicity is a potentially fatal AE, and introduces new challenges regarding its underlying molecular mechanisms of occurrence, optimal treatment and follow up, and prevention. We present a clinical case of a patient with advanced kidney cancer treated with nivolumab as a third line treatment. After four cycles, the patient developed nonspecific symptoms and was hospitalized, identifying a set of clinical, analytical and electrocardiographic alterations compatible with myocarditis. Despite the intensive support, the patient died and a necropsy study was performed. We present a detailed description of the clinical case including the pathological and molecular findings, and we conduct a review of the available evidence related to immune-mediated cardiac toxicity to offer some new highlights in the management of this AE.