Familial rare EGFR-mutant lung cancer syndrome: Review of literature and description of R776H family.

BACKGROUND: Interest in hereditary lung cancer is increasing, in particular germline mutations in the Epidermal Growth Factor Receptor (EGFR) gene. We review the current literature on this topic, discuss risk of developing lung cancer, treatment and screening options and describe a family of 3 sisters with lung cancer and their unaffected mother all with a rare EGFR germline mutation (EGFR p.R776H). METHODS: We searched PubMed, Medline, Embase, the Cochrane Library, Google Scholar and scanned reference lists of articles. Search terms included "EGFR germline" and "familial lung cancer" or "EGFR familial lung cancer". We also describe our experience of managing a family with rare germline EGFR mutant lung cancer. RESULTS: Although the numbers are small, the described cases in the literature show several similarities. The patients are younger and usually have no or light smoking history. 50% of the patients were treated with a tyrosine kinase inhibitor (TKIs) with OS over six months. CONCLUSION: Although rare, germline p.R776H EGFR lung cancer mutations are over-represented in light or never smoking female patients who often also possess an additional somatic EGFR mutation. Treatment with TKIs appears suitable but further research is needed into the appropriate screening regime for unaffected carriers or light/never smokers.

The Predictive Value of the G8 Questionnaire in Older Patients with Lung Cancer or Mesothelioma before Systemic Treatment.

AIMS: The standard evaluation of older lung cancer or mesothelioma patients for systemic anti-cancer treatment, based on performance status, is inaccurate. We used the G8 questionnaire to assess a patient's fitness for chemotherapy and explored the correlations between G8 scores, treatment decisions and clinical outcomes. MATERIALS AND METHODS: In total, 201 older patients (≥70 years) with advanced lung cancer or mesothelioma were prospectively assessed by standard clinical methods and a G8 questionnaire. Treatment decisions before and after reviewing the G8 score were documented. Patients were divided into low (<11), intermediate (11-14) and high (>14) G8 score groups. Patients' characteristics, treatment plans and clinical outcomes among each G8 score group were compared. Similar analyses were compared between good (<2) and poor (≥2) performance status. RESULTS: 10.1% of patients' treatment plans changed after oncologists reviewed G8 scores. The G8 score correlated inversely with performance status. More patients with low G8 scores (22.5%) were offered the best supportive care compared with 4.5% in intermediate and 1.9% in high G8 score groups. More patients (30.1%) with low G8 scores had treatment changed from chemotherapy to best supportive care on the planned day of their treatment, compared with intermediate (7.5%) and high (6.1%) G8 score groups. High G8 score patients received higher chemotherapy intensity and survived longer than patients with intermediate or low G8 scores. CONCLUSIONS: The G8 score with two cut-off values can predict functional status, chemotherapy tolerability and prognosis in older patients with lung cancer or mesothelioma, thus supporting oncologists on treatment decisions for this population.