Lucia Ceniceros

Stereotactic body radiotherapy (SBRT) for the treatment of inoperable stage I non-small cell lung cancer patients

IntroductionLung cancer is the most frequent neoplasm in humans. Surgery is considered the best therapeutic approach for stage I non-small lung cell cancer (NSCLC). However, a remarkable amount of patients are considered as inoperable. Stereotactic body radiotherapy (SBRT) has risen as an option for those patients, rendering excellent results in quality of life and survival.Materials and methodsWe analyzed clinical studies published between 2002 and 2015 which included SBRT as a treatment modality. Our own clinical series was analyzed as well. The patterns of failure following SBRT were investigated, together with the outcomes and the toxicity observed.ResultsSBRT has proven to maintain an excellent local control. The analysis showed the tumor size and the histology as determinant factors for the response to treatment.ConclusionAccording to the published evidence as well as our own experience, SBRT is a safe and feasible approach for early NSCLC. Its results may be comparable with surgery treatment.

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.

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.

1634PINHIBITOR OF DIFFERENTIATION-1 (ID1) AND ID3 EXPRESSION CORRELATES WITH EPITHELIAL-MESENCHYMAL TRANSITION (EMT)-RELATED PROTEINS (EMTRP) IN NON-SMALL CELL LUNG CARCINOMA (NSCLC)

ABSTRACT Aim: We previously reported the prognostic impact of Id1 in all NSCLC stages and of the combined Id1/Id3 expression in stage III-N2 patients undergoing radical chemo-radiotherapy. Further, we found that Id1 expression in the tumor microenvironment is crucial for the development of liver metastasis from lung cancer in an in-vivo model. In other neoplasms, Id genes are considered to be regulators of EMT-facilitated metastasis. Here we study Id1 and Id3 combined expression in a large NSCLC cohort and its correlation with EMTrp and overall survival (OS). Methods: Three tissue microarrays of 538 NSCLCs including 284 squamous-cell carcinomas (SCC) and 254 adenocarcinomas (AC) were stained by immunohistochemistry using the following antibodies: Sox10, Beta-catenin, E-cadherin, Vimentin, Slug, Podoplanin, S6, ERCC1, Id1 and Id3. Immunoreactivity was H-scored for intensity (range 0 to 3) multiplied by percentage of positive cells and computed by Spearmans Rho correlation test. Results: Among SCC histology a significant positive correlation was observed between the combined expression of Id1 and Id3 and the expression of Sox10, Beta-catenin, E-Cadherin, Slug, Podoplanin and ERCC1. In the AC subset, significant positive correlations were found between Id1/Id3 and Beta-catenin, E-Cadherin, Vimentin, pS6, and ERCC1. As expected, Id1/Id3 expression showed a negative correlation with OS (r= -0.157; p=0.013). Protein SCC AC (n.s; not significant) r p value r p value Sox10 0.146 0.018 n.s. n.s. Beta-Catenin 0.218 0.001 0.161 0.01 E-cadherin 0.128 0.038 0.150 0.017 Vimentin n.s. n.s. 0.147 0.019 Slug 0.187 0.002 n.s. n.s. Podoplanin 0.127 0.039 n.s. n.s. S6 n.s. n.s. 0.150 0.014 ERCC1 0.265 0.001 0.185 0.003 Conclusions: In NSCLC, the combined expression of Id1 and Id3 negatively correlated with OS and positively with several key EMTrp, suggesting a possible key regulation of the EMT process favoring vessel infiltration and distant organ metastasis, respectively. Disclosure: All authors have declared no conflicts of interest.

645PINDUCTION CHEMOTHERAPY, CHEMO-RADIOTHERAPY AND SURGERY IN LOCALLY ADVANCED GASTRIC CANCER (GC) PATIENTS: LONG TERM RESULTS FROM A SINGLE INSTITUTION

ABSTRACT Aim: Multimodal therapy is the standard of care in locally advanced esophagogastric adenocarcinomas. However, most trials include both, GEJ and GC. We aimed to specifically rule out in gastric cancer patients the R0 rate, pathological response degree, patterns of recurrence and long-term outcomes when treated with induction chemotherapy (ICT), followed by chemoradiotherapy (CRT) and salvage surgery. Methods: Patients (pts) with CT scan and endoscocopic ultrasound (EUS) T2-4 and/or N+ M0 GC were retrospectively analyzed. The neoadjuvant strategy consisted of 3-4 cycles of chemotherapy followed by CRT (weekly chemotherapy concurrently with daily external beam radiotherapy up to 45 Gy). Surgery was scheduled 4 to 6 weeks after the end of CRT. Pathological response was graded according to the Becker criteria. We have applied a nonlinear mixed effects (NLME) modeling to evaluate the impact of dynamic changes in tumor size, neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) on the clinical outcome of these patients. Results: From November 2004 to July 2013, 60 pts [M/F: 42/18, median age 60 (range 36-76), T2/T3/T4a/T4b: 2/24/26/8; N0/N + , 6/54; Diffuse/Intestinal: 35/25] were retrospectively analyzed. Thirty-four and 54 patients were stages by EUS as T4 or N +, respectively. Median preoperative NLR and PLR were both 2.43 and 148. Forty-nine pts underwent radical surgery (total/partial gastrectomy: 33/16) with an R0 resection rate of 92%. Pathological response according to Becker criteria was grade Ia (12%), grade Ib (39%), grade II (22%) and grade III (2%). pN0 was achieved in 26 pts (53,1%). Median harvested nodes were 13. Median DFS for pN0 and pN+ pts was NR and 23 months, respectively (p = 0.01), whereas median OS for pN0 and pN+ was NR and 30 months, respectively (p = 0.009). Among resected pts, distant failures were reported 22 pts, most of them in the peritoneal cavity (55%). After a median follow-up of 30 months (range 4-95 months) the 5-year overall and disease-free survival, were 31% and 39%, respectively. Conclusions: Our data suggest that a three-step strategy is feasible and active in locally advanced gastric cancer patients. The NMLE population modeling to evaluate the impact of dynamic markers on the clinical outcome will be presented at the meeting. Disclosure: All authors have declared no conflicts of interest.

644PINDUCTION CHEMOTHERAPY FOLLOWED BY CHEMORADIOTHERAPY IN LOCALLY ADVANCED ESOPHAGOGASTRIC ADENOCARCINOMA. HAS THE LOCATION OF THE PRIMARY TUMOR ANY INFLUENCE ON PATIENTS' OUTCOME? A RETROSPECTIVE ANALYSIS

ABSTRACT Aim: Multimodal therapy is the standard of care in locally advanced esophagogastric adenocarcinoma. However, most trials include both, gastric (GC) and gastroesophageal junction (GEJ) cancers. We aimed to rule out whether patients (pts) with either locally advanced GEJ (group A) or GC (group B) have different outcomes when treated with a neoadjuvant approach based on induction chemotherapy (ICT), chemoradiotherapy (CRT) and surgery. Methods: EUS-T2-4 and/or N+ M0 GEJ or GC adenocarcinoma patients were scheduled to receive preoperative therapy (3-4 cycles of chemotherapy followed by concurrent CRT). Surgery was scheduled 4 to 6 weeks after the end of CRT. Pathological response was graded according to the Becker criteria. Patterns of recurrence, progression-free survival (PFS) and overall survival (OS) were also evaluated. Results: From november 2004 to July 2013, 87 pts (27 in group A, 60 in group B) met the specified criteria. Pts characteristics were; Group A; M/F; 23/4; EUS-T3 52%, T4 40,7%, N+ 95%, median age 56 (31-81); Diffuse/Intestinal 55%/44%. Group B; M/F; 42/18; EUS-T3 40%, T4 56%, N+ 95%; median age 60.5 (36-76); Diffuse/Intestinal 57%/42%. Seventy-four pts underwent surgery (group A/ B; 92.6%/82%). Pathological response (Group A/B); Grade Ia-Ib according to Becker criteria (72%/51%), pN0 (60.3%/53%). R0 resection (Group A/B); (96%/94%). Among resected pts we analysed the impact of tumor location (GC vs GEJ) on known prognostic factors such as Lauren classification and degree of pathological response regarding PFS and OS. In group A, median OS and PFS did not difer according to Lauren neither classification nor pN status. In contrast, median PFS varied according to Becker response (Ia-b: Not Reached; II-III: 13m; p = 0.02). In group B, we found differences in PFS and OS according to; a)- Lauren Classification; Intestinal GC vs Diffuse GC pts [median PFS; NR vs 13.6m; p = 0.028, median OS: NR vs 15.3m; p = 0.026]. b)pN status (-/+) [median PFS; NR vs 18m; p Conclusions: When treated with ICT followed by CRT, GEJ and GC pts have different outcomes in terms of pathological response degree, patterns of recurrence and survival times. Disclosure: All authors have declared no conflicts of interest.