Meeting Abstract

JL428. Symptoms and Management of Cerebral Progression in Patients With Anaplastic Lymphoma Kinase-Positive (ALK+) Non-Small Cell Lung Cancer (NSCLC): A Clinical and Nursing Perspective

Rachael Pollina, MS, MSN, FNP-BC, Memorial Sloan Kettering Cancer Center, New York, NY, Wendi Stone, RN, NP-C, University of Texas MD Anderson Cancer Center, Houston, TX, Kate Kegg, MPAS, PA-C, University of Texas MD Anderson Cancer Center, Houston, TX, and Anne S. Tsao, MD, University of Texas MD Anderson Cancer Center, Houston, TX

ABSTRACT

Background: Around 30–50% of ALK+ NSCLC patients have brain metastases (BM) before initiating ALK inhibitor (ALKi) treatment. In general, the prognosis for patients with BM is poor (median survival 7 months). Standard treatments include surgery, stereotactic radiosurgery (SRS), and whole-brain radiotherapy (WBRT). However, patients with ALK+ NSCLC and BM are a unique group, with prolonged survival when treated with SRS/WBRT and ALKis. Up to 50% of ALK+ NSCLC patients will have BM at presentation or at time of first progression. With second/third-generation ALKis that cross the blood–brain barrier, intracranial disease control can be temporarily achieved. However, cerebral progression can eventually occur (0–21% across second-generation ALKi clinical studies). It is well established that the number of metastatic CNS sites significantly impacts prognosis and treatment options. Delayed detection of progression may result in increased disease burden and decreased survival. Therefore, routine surveillance with vigilant CNS monitoring is required to facilitate early identification of patients with disease progressing in the brain. The signs and symptoms of cerebral progression include:

Headaches
Nausea/vomiting
Weakness
Progressive neurologic deficit (e.g. partial paralysis, speech impediments)
Seizures
Sensory defects (e.g. visual impairment)
Gait abnormalities
Cognitive impairment (confusion/memory loss)

Treatment strategies include dexamethasone for edematous and symptomatic BM, and anticonvulsants for seizure prevention. It is important to distinguish the effects of new BM from radiotherapy-induced radionecrosis, as this can present as an edematous growing mass on imaging. Likewise, some ALKi side effects can be difficult to differentiate from symptoms of new BM (e.g. visual disturbances, nausea/vomiting). The side effects of treatments for symptoms must also be managed; strategies include minimizing/tapering corticosteroid doses and adjustment of anticonvulsants based on altering symptoms. Recommendations: As soon as symptoms of BM are recognized, primary oncology healthcare providers should reach out to neurosurgeons/neurologists/neuro-oncologists and CNS radiotherapists as appropriate. ALK+ NSCLC patients require regular interval follow-ups for focused neurologic assessment with recent imaging results. Ophthalmologists should be consulted to manage visual disturbance. Physical therapy may help manage aerobic incapacity, weakness, balance/coordination, and visual-perceptual impairment. Initiation of BM treatment, including switching ALKi therapy, should be considered (it is recommended that ALKis are held during WBRT). Conclusions: Early identification of CNS progression has the potential to improve ALK+ NSCLC patient prognosis by providing an opportunity for rapid and timely intervention. Repeated treatment of CNS disease with ALKis/SRS is becoming the new standard of care, with ALKis preferred over WBRT.

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