Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melanoma brain metastases (MBM) are common and associated with a particularly poor prognosis; they directly cause death in 60-70% of melanoma patients. In the past, systemic treatments have shown response rates around 5%, whole brain radiation as standard of care has achieved a median overall survival of approximately three months. Recently, the combination of immune checkpoint inhibitors and combinations of MAP-kinase inhibitors both have shown very promising response rates of up to 55% and 58%, respectively, and improved survival. However, current clinical evidence is based on multi-cohort studies only, as prospectively randomized trials have been carried out rarely in MBM, independently whether investigating systemic therapy, radiotherapy or surgical techniques. Here, an interdisciplinary expert team reviewed the outcome of prospectively conducted clinical studies in MBM, identified evidence gaps and provided recommendations for the diagnosis, treatment, outcome evaluation and monitoring of MBM patients. The recommendations refer to four distinct scenarios: patients (i) with 'brain-only' disease, (ii) with oligometastatic asymptomatic intra- and extracranial disease, (iii) with multiple asymptomatic metastases, and (iv) with multiple symptomatic MBM or leptomeningeal disease. Changes in current management recommendations comprise the use of immunotherapy - preferably combined anti-CTLA-4/PD-1-immunotherapy - in asymptomatic MBM minus/plus stereotactic radiosurgery which remains the mainstay of local brain therapy being safe and effective. Adjuvant whole-brain radiotherapy provides no clinical benefit in oligometastatic MBM. Among the systemic therapies, combined MAPK-kinase inhibition provides, in BRAFV600-mutated patients with rapidly progressing or/and symptomatic MBM, an alternative to combined immunotherapy.
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PMID:Melanoma brain metastases - Interdisciplinary management recommendations 2020. 3273 88

Approximately one-fourth of osteosarcoma patients have metastases at presentation. The best treatment options for these patients include chemotherapy, surgery, and radiotherapy; however, the optimal scheme has not yet been defined. Standard chemotherapy for osteosarcoma metastatic at presentation is based on high-dose methotrexate, doxorubicin, and cisplatin (the MAP regimen), with the possible addition of ifosfamide. Surgical treatment continues to be fundamental; complete surgical resection of all sites of disease (primary and metastatic) remains essential for survival. In patients whose tumors do not respond to neoadjuvant chemotherapy, early surgical resection of the primary tumor with limb-salvage surgery or amputation and multiple metastasectomies, if feasible, after the completion of adjuvant chemotherapy is a reasonable option, as the reduction of the tumor volume could probably increase the effect of chemotherapy. Advanced radiotherapy techniques, such as carbon ion radiotherapy and stereotactic radiosurgery, and molecular targeted chemo-therapy with drugs such as pazopanib or apatinib have improved the dismal prognosis, especially for patients who are medically inoperable or who refuse surgery. Given that the presence of metastatic disease at diagnosis of a patient with osteosarcoma is a poor prognostic factor, a multidisciplinary approach by surgeons, medical oncologists, and radiotherapists is important. [Orthopedics. 2020;43(5):e345-e358.].
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PMID:Current Treatment Considerations for Osteosarcoma Metastatic at Presentation. 3274 18


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