Objective response rates to erlotinib and gefitinib are higher in patients who have never smoked, in females, in East Asians, and in patients with adenocarcinoma and bronchioloalveolar carcinoma.[23,24,25,26,27,28,29] Responses may be associated with sensitizing mutations in the tyrosine kinase domain of the EGFR [24,25,26,28,29] and with the absence of K-RAS mutations.[27,28,29][Level of evidence: 3iiiDiii] Survival benefit may be greater in patients with EGFR protein expression by immunohistochemistry or increased EGFR gene copy number by fluorescence in situ hybridization studies,[28,29] although the clinical utility of EGFR testing by immunohistochemistry has been questioned.
Treatment of second primary tumor
A solitary pulmonary metastasis from an initially resected bronchogenic carcinoma is unusual. The lung is frequently the site of second primary malignancies in patients with primary lung cancers. Whether the new lesion is a new primary cancer or a metastasis may be difficult to determine. Studies have indicated that in most patients the new lesion is a second primary tumor, and after its resection, some patients may achieve long-term survival. Thus, if the first primary tumor has been controlled, the second primary tumor should be resected, if possible.[31,32]
Treatment of brain metastases
Patients who present with a solitary cerebral metastasis after resection of a primary NSCLC lesion and who have no evidence of extracranial tumor can achieve prolonged DFS with surgical excision of the brain metastasis and postoperative whole-brain radiation therapy (WBRT).[33,34] Unresectable brain metastases in this setting may be treated with radiation surgery.
Because of the small potential for long-term survival, radiation therapy should be delivered by conventional methods in daily doses of 1.8 Gy to 2.0 Gy. Because of the high risk of toxic effects observed with such treatments, higher daily doses over a shorter period of time (i.e., hypofractionated schemes) should be avoided. Most patients who are not suitable for surgical resection should receive conventional WBRT.
Approximately 50% of patients treated with resection and postoperative radiation therapy will develop recurrence in the brain; some of these patients will be suitable for additional treatment. In those selected patients with good PS and without progressive metastases outside of the brain, treatment options include reoperation or stereotactic radiation surgery.[8,10] For most patients, additional radiation therapy can be considered; however, the palliative benefit of this treatment is limited.[Level of evidence: 3iiiDiii]