Role of histological regression grade after two neoadjuvant approaches with or without radiotherapy in locally advanced gastric cancer.

BACKGROUND: The degree of histopathological response after neoadjuvant therapy in locally advanced gastric cancer (GC) is a key determinant of patients' long-term outcome. We aimed to assess the pattern of histopathological regression after two neoadjuvant approaches and its impact on survival times. METHODS: Regression grade of the primary tumour (Becker criteria) and the degree of nodal response by a 4-point scale (grades A-D) were assessed. Grade A-true negative lymph nodes (LNs); grade B and C-infiltrated LNs with any or little evidence of nodal response; and grade D-complete pathological response in a previously infiltrated LN. A favourable pathological response was defined as Becker Ia-b and grade D. RESULTS: From 2004 to 2014, 80 patients with GC (cT3-4/N+ by CT-scan/EUS) were treated with either preoperative chemotherapy (ChT, n=34) or chemoradiation (CRT, n=46). Patients in the CRT group had a higher likelihood of achieving a Becker Ia-b response (58 vs 32%, P=0.001), a grade D nodal regression (30 vs 6%, P=0.009) and a favourable pathological response (23 vs 3%; P=0.019). Patients with a grade D nodal response had a longer 5-year PFS and OS compared with those with a grade B or C response. Patients with a baseline negative LN status had similar outcomes irrespective of the preoperative therapy received (5-year OS; ChT vs CRT, 58 vs 51%, P=0.92). CONCLUSIONS: Preoperative chemoradiation increases the likelihood of achieving favourable histopathological features that correlate with a 5-year OS>70% in GC patients.

Epidermal Growth Factor Receptor targeting in non-small cell lung cancer: revisiting different strategies against the same target.

Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the paradigm of treatment in non-small cell lung cancer (NSCLC). The molecular biology study of EGFR has led to clinical trials that select patients more accurately, regarding the presence of EGFR activating mutations. Nonetheless, a lack of response or a temporary condition of the response has been detected in patients on EGFR TKIs. This has urged to study potential resistance mechanisms underneath. The most important ones are the presence of secondary mutations in EGFR, such as T790M, or the overexpression of mesenchymal-epithelial transition factor (MET) that may explain why patients who initially respond to EGFR TKIs, may ultimately become refractory. Several approaches have been taken and new drugs both targeting EGFR resistance-mutation or MET are currently being developed. Here we review and update the EGFR biological pathway as well as the clinical data leading to approval of the EGFR TKIs currently in the market. New compounds under investigation targeting resistance mutations or dually targeting EGFR and other relevant receptors are also reviewed and discussed.