Abstract
Developments in the treatment of advanced melanoma
Patients with melanomas ≥1 mm thick undergo a sentinel node biopsy. The sentinel node is the hypothetical first lymph node or group of nodes draining a cancer. It has been postulated that this procedure increases intralymphatic metastases, however, our systematic review showed no causal relationship.
Patients with limited cutaneous metastases may be candidates for intratumoral therapy. For patients with metastases confined to extremities or liver, regional perfusion and infusion techniques may be a valid option. These treatments are effective, with less morbidity than systemic therapy.
About 50% of patients with disseminated disease will harbor the BRAF V600E mutation and will benefit from systemic BRAF targeted therapy. The current thesis presents a case series of patients treated with neoadjuvant (i.e. systemic treatment administered before surgical removal of the tumor) BRAF targeted therapy, which might lead to a prolonged survival in select patients. Further (randomized) research is needed to support this hypothesis generating study. However, this treatment has been observed to lead to paradoxical activation of proliferative cellular pathways, which may lead to secondary malignancies. Adding MEK inhibitors decreases this risk.
Lastly, this thesis shows that the prognosis of patients with melanoma brain metastases (MBM) has much improved and that the choice of systemic treatment does not affect MBM incidence. Overall survival, measured from MBM diagnosis, increased from 7.2 months for patients diagnosed in 2000-2008 to 22.8 months for patients diagnosed from 2011-present.
Despite recent advancements, treatment of advanced melanoma thus still represents an unmet medical need.
Patients with melanomas ≥1 mm thick undergo a sentinel node biopsy. The sentinel node is the hypothetical first lymph node or group of nodes draining a cancer. It has been postulated that this procedure increases intralymphatic metastases, however, our systematic review showed no causal relationship.
Patients with limited cutaneous metastases may be candidates for intratumoral therapy. For patients with metastases confined to extremities or liver, regional perfusion and infusion techniques may be a valid option. These treatments are effective, with less morbidity than systemic therapy.
About 50% of patients with disseminated disease will harbor the BRAF V600E mutation and will benefit from systemic BRAF targeted therapy. The current thesis presents a case series of patients treated with neoadjuvant (i.e. systemic treatment administered before surgical removal of the tumor) BRAF targeted therapy, which might lead to a prolonged survival in select patients. Further (randomized) research is needed to support this hypothesis generating study. However, this treatment has been observed to lead to paradoxical activation of proliferative cellular pathways, which may lead to secondary malignancies. Adding MEK inhibitors decreases this risk.
Lastly, this thesis shows that the prognosis of patients with melanoma brain metastases (MBM) has much improved and that the choice of systemic treatment does not affect MBM incidence. Overall survival, measured from MBM diagnosis, increased from 7.2 months for patients diagnosed in 2000-2008 to 22.8 months for patients diagnosed from 2011-present.
Despite recent advancements, treatment of advanced melanoma thus still represents an unmet medical need.
| Original language | English |
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| Qualification | Doctor of Philosophy |
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| Award date | 22-Nov-2017 |
| Place of Publication | [Groningen] |
| Publisher | |
| Print ISBNs | 978-94-6233-755-8 |
| Publication status | Published - 2017 |