A distinct four-value blood signature of pyrexia under combination therapy of malignant melanoma with dabrafenib and trametinib evidenced by an algorithm-defined pyrexia score

Pyrexia is a frequent adverse event of BRAF/MEK-inhibitor combination therapy in patients with metastasized malignant melanoma (MM). The study’s objective was to identify laboratory changes which might correlate with the appearance of pyrexia. Initially, data of 38 MM patients treated with dabrafenib plus trametinib, of which 14 patients developed pyrexia, were analysed retrospectively. Graphical visualization of time series of laboratory values suggested that a rise in C-reactive-protein, in parallel with a fall of leukocytes and thrombocytes, were indicative of pyrexia. Additionally, statistical analysis showed a significant correlation between lactate dehydrogenase (LDH) and pyrexia. An algorithm based on these observations was designed using a deductive and heuristic approach in order to calculate a pyrexia score (PS) for each laboratory assessment in treated patients. A second independent data set of 28 MM patients, 8 with pyrexia, was used for the validation of the algorithm. PS based on the four parameters CRP, LDH, leukocyte and thrombocyte numbers, were statistically significantly higher in pyrexia patients, differentiated between groups (F = 20.8; p = <0.0001) and showed a significant predictive value for the diagnosis of pyrexia (F = 6.24; p = 0.013). We provide first evidence that pyrexia in patients treated with BRAF/MEK-blockade can be identified by an algorithm that calculates a score

The use of circulating cell-free tumor DNA in routine diagnostics of metastatic melanoma patients

Modern advances in technology such as next-generation sequencing and digital PCR make detection of minor circulating cell-free tumor DNA amounts in blood from cancer patients possible. Samples can be obtained minimal-invasively, tested for treatment-determining genetic alterations and are considered to reflect the genetic constitution of the whole tumor mass. Furthermore, tumor development can be determined by a time course of the quantified circulating cell-free tumor DNA. However, systematic studies which prove the clinical relevance of monitoring patients using liquid biopsies are still lacking. In this study, we collected 115 samples from 47 late stage melanoma patients over 1.5 years alongside therapy-associated clinical routine monitoring. Mutation status was confirmed by molecular analysis of primary tumor material. We can show that detectable levels of circulating cell-free tumor DNA correlate with clinical development over time. Increasing levels of circulating cell-free tumor DNA during melanoma treatment with either targeted therapy (BRAF/MEK inhibitors) or immunotherapy, during recovery time or the intervals between last treatment cycle and second-line treatment point towards clinical progression before the progression becomes obvious in imaging. Therefore, this is a further possibility to closely screen our patients for tumor progression during therapy, in therapy-free phases and in earlier stages before therapy initiation

What is new in the diagnosis and therapy of malignant melanoma?

Melanoma incidence and mortality rates are increasing. The sentinel lymph node biopsy plays an important prognostic role and is pivotal for the decision to undergo an adjuvant therapy making it an important diagnostic tool. The lack of survival benefit in patients with sentinel lymph node-positive (SLN+) melanoma upon immediate complete lymphadenectomy (CLND) suggest a parallel and not stepwise development of lymph node metastasis and distant metastasis thus questioning the role of immediate CLND. These findings also suggest adjuvant therapy may play a more important role for SLN+ melanoma patients than CLND. Recently, the PD-1 inhibitor Nivolumab and Pembrolizumab as well as the BRAF/MEK inhibitor Dabrafenib and Trametinib were approved for the adjuvant therapy of stage III malignant melanoma. Another novelty in the therapy of malignant melanoma is the approval of the first oncolytic virus, Talimogene laherparepvec, for the treatment of unresectable stage III and IV (M1a) melanoma. Significant progress has also been made in the treatment of patients with cerebral melanoma metastasis since studies indicate that both BRAF/MEK inhibitors and the immunotherapy with CTLA4 and PD-1 inhibitors are efficient in this group of patients. With this wide range of possible systemic therapies for advanced melanoma further studies regarding therapy sequence, combinations between targeted therapies and immunotherapy as well as biomarkers for treatment response are needed to help guide physicians find the optimal therapy for patients with advanced malignant melanoma

Predicting risk for seroma development after axillary or inguinal sentinel lymph node biopsy in melanoma patients

Background Sentinel lymph node biopsy (SLNB) is currently a routine procedure in the staging of patients with cutaneous melanoma; however, little information is available about the risk factors for postoperative complications, especially for the risk of seroma formation. Methods Medical records of patients undergoing SLNB at the University Hospital of Cologne, Germany, between 2011 and 2016, were reviewed. Binary logistic regression was used to analyze the influence of a wide range of variables on seroma development. Results A total of 615 patients were included in the study. Overall, 20.4% of patients developed complications with seroma being the most common postoperative complication. Development of seroma was significantly more common among smokers than nonsmokers (OR = 1.956, P = 0.007). Inguinal localization (OR = 3.644, P < 0.0001) was also associated with seroma formation. Male patients developed a seroma significantly more often than female patients following SLNB (OR = 2.104, P = 0.001). The presence or absence of metastasis in the lymph node did not influence seroma development. Conclusions Male sex, inguinal localization, and smoking are risk factors for the development of seroma