Efflorescence of scalp cysts during vemurafenib treatment following brain radiation therapy: a radiation recall dermatitis?

Avoiding Severe Toxicity From Combined BRAF Inhibitor and Radiation Treatment: Consensus Guidelines from the Eastern Cooperative Oncology Group (ECOG)

“…Follicular cystic lesions have been described by multiple authors (18, 23, 28, 47). Schulze and colleagues (31) reported on a patient in whom miliary cystic lesions developed 1 month after concurrent vemurafenib and WBRT only in the RT field.…”

“…Clinically, there have been reports of increased dermatologic (16-33), lung (20), liver (16), esophageal (22, 34), brain (26, 35), and bowel toxicity (26) when RT has been given concurrently with or in proximity to BRAFi, including both vemurafenib and dabrafenib. Severe dermatitis has been reported during RT when given concurrently with a BRAFi, and it has also been described as an RT recall reaction despite starting a BRAFi many weeks after RT completion (18, 20, 21, 23, 24, 27, 28, 33, 36, 37). RT dermatitis can often be managed effectively with topical or systemic steroids and analgesics as needed, sometimes without BRAFi cessation.…”

Radiotherapy with BRAF Inhibitor Therapy for Melanoma: Progress and Possibilities

“…This may manifest itself as common radiodermatitis but also, and even more strikingly, as cutis verticis gyrata-like skin lesions characterized by general erythema and edema and the presence of excessive cysts and milia. A pronounced formation of cutis verticis gyratalike skin lesions during or after whole-brain radiotherapy in combination with vemurafenib has been described in one out of two cases by Schulze et al [65] -the other patient developed radiodermatitis -as well as in a single patient each by Lang et al [67], Reigneau et al [68] and Forschner et al [62]. In a retrospective study on 27 melanoma patients of which 12 have been treated by a concomitant (n = 11) or sequential (n = 1) protocol of vemurafenib and whole-brain radiotherapy (n = 10) or stereotactic radiosurgery (n = 2), Harding et al [63,64] described the appearance of cutis verticis gyrata in two patients 3 weeks after the start of vemurafenib therapy concomitant to or 6 weeks after whole-brain radiotherapy as well as the formation of radiodermatitis (CTCAE grade 2) in one out of nine patients who started vemurafenib therapy after whole-brain radiotherapy.…”

“…Radiation recall cutis verticis gyrata after radiation treatment of the scalp occurred later, between 14 and 28 days (median: 21 days) after start of BRAF inhibitor therapy which had been preceded by whole-brain radiotherapy [62][63]67]. Collectively, cutis verticis gyrata-like skin lesions had a latency period until full expression between 28 and 63 days (median: 39 days) after the completion of whole-brain radiotherapy irrespective of the timing of BRAF inhibitor application, in other words, before [65,68], during [63] or after radiotherapy [62][63]67]. These delayed pathologies of the skin after radiotherapy and subsequent vemurafenib occurred earlier than nondermatological delayed radiation effects like radiation recall pneumonitis, which has been observed 21 and 28 days after the start of vemurafenib s ubsequent to radiotherapy [62].…”

Safety and Tolerability of Metastasis-Directed Radiation Therapy in the Era of Evolving Systemic, Immune, and Targeted Therapies

“…When BRAF inhibitors are combined with RT, the most commonly report side effect is dermatitis, occurring during or within 7 days of RT [10][11][12][13][14][15][16][17][18][19][20][21][22][23] . In addition to acute skin toxicities, there have been a number of case reports of radiation recall, associated with systemic agents that have started more than 7 days from RT completion,with no Common Terminology Criteria for Adverse Events (CTCAE) grade 3 higher toxicity reported, and subsequently managed conservatively Reported toxicities were more commonly seen in the SBRT plus pembrolizumab and trametinib arm, with CTCAE grade 3-4 increased liver enzymes (12% vs 7%) and increased bilirubin (5% vs 0%), with no treatment related deaths occurred.…”