Safety of cranial radiotherapy concurrent with tyrosine kinase inhibitors in non-small cell lung cancer patients: A systematic review

Abstract

Recently, non-small cell lung cancer (NSCLC) has been partly subclassified into molecularly-defined oncogene "addicted" tumors for which targeted agents are available. Tyrosine kinase inhibitors (TKI) are currently approved for patients with an activating epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement. In these patients, brain metastases are often the first site of progression while on TKI treatment. The TKI may however still be active on extra-cranial sites and clinicians are thus faced with the question if the TKI may be continued during cranial radiotherapy. Advantages of combining TKI with cranial radiotherapy would be a possible synergistic effect on the brain metastases and the prevention of a systemic disease flare-up. A disadvantage is the possibly increased risk of (neuro)toxicity. The present systematic review addresses the toxicity of combining TKI with cranial radiotherapy in NSCLC patients.

Efficacy of EGFR‐TKIs with or without upfront brain radiotherapy for EGFR‐mutant NSCLC patients with central nervous system metastases

“…According to a systematic review reported by Hendriks et al . most of nine trials showed no increased neurotoxicity in TKI plus brain radiotherapy compared to TKI alone . Whereas, another retrospective study reported increase of memory impairment in TKI plus WBRT compared to TKI alone .…”

“…According to a systematic review reported by Hendriks et al most of nine trials showed no increased neurotoxicity in TKI plus brain radiotherapy compared to TKI alone. 32 Whereas, another retrospective study reported increase of memory impairment in TKI plus WBRT compared to TKI alone. 17 Two randomized phase 3 studies of solid tumors with one to three BMs showed that SRS plus WBRT impaired health-related QOL and cognitive function, respectively, and did not improve OS compared to SRS alone.…”

Management of non-small cell lung cancer with EGFR mutation: the role of radiotherapy in the era of tyrosine kinase inhibitor therapy—opportunities and challenges

“…These results suggest that TKI can be considered as the first choice if the primary goal was to achieve prompt symptomatic relief. It is unclear whether delivery of concomitant radiotherapy can be resulted in better outcomes, but such an approach of combined treatment deserved additional studies to explore, considered of the favorable toxicity profile when radiotherapy combined with TKI therapy reported in literatures (20,21).…”

“…Concomitant use of TKI may have the advantage of a synergistic effect on the brain metastases, but at the price of possibly increased risk of neurotoxicity. Such attempt had been reported in a lot of retrospective and prospective studies, but often with small sample size (20). Primary outcomes in these studies varied and the data were measured and reported in a nonuniform way.…”

Integration of Stereotactic Body Radiation Therapy With Tyrosine Kinase Inhibitors in Stage IV Oncogene-Driven Lung Cancer

“…The Oncologist 2016; 21:964-973 Implications for Practice: Stereotactic body radiation therapy (SBRT) or SBRT-like treatments are increasingly being used for oligoprogression in patients with oncogene-driven non-small cell lung cancer.This approach allows patients to extend the duration of tyrosine kinase inhibitor therapy and has the potential to prolong survival times. Careful patient selection and risk-adapted radiation dosing is of critical importance to minimize toxicity and preserve patient quality of life.The Oncologist 2016;21:964-973 www.TheOncologist.com ©AlphaMed Press 2016 reports on this topic [11][12][13][14][15].The reader is also referred to other recent reviews on the role of local therapies for patients with oligometastatic or oligoprogressive disease [16][17][18][19][20][21][22].…”