Resectable gastric or gastroesophageal (G/GEJ) cancer is a heterogeneous disease with no defined molecularly based treatment strategy. Unfortunately, nearly half of patients experience disease recurrence despite standard treatments (neoadjuvant and/or adjuvant chemotherapy/chemoradiotherapy and surgery). In this review, we summarize the evidence of potential tailored approaches in perioperative treatment of G/GEJ cancer, with a special focus on patients with human epidermal growth factor receptor-2(HER2)-positive and microsatellite instability-high (MSI-H) tumors. In patients with resectable MSI-H G/GEJ adenocarcinoma, the ongoing INFINITY trial introduces the concept of non-operative management for patients with complete clinical-pathological-molecular response, and this could be a novel and potential practice changing strategy. Other pathways involving vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), claudin18 isoform 2 (CLDN18.2), and DNA damage repair proteins are also described, with limited evidence until now. Although tailored therapy appears to be a promising strategy for resectable G/GEJ cancer, there are several methodological issues to address: inadequate sample size for pivotal trials, underestimation of subgroup effects, and choice of primary endpoint (tumor-centered vs. patient-centered endpoints). A better optimization of G/GEJ cancer treatment allows maximizing patient outcomes. In the perioperative phase, although caution is mandatory, times are changing and tailored strategies could introduce new treatment concepts. Overall, MSI-H G/GEJ cancer patients possess the characteristics to be the subgroup that could receive the most benefit from a tailored approach.

Colorectal cancer (CRC) is the third most common cancer worldwide, with approximately 1.9 million new diagnoses and 935 000 deaths annually. Overall, there is accumulating evidence that receiving all available treatments leads to a survival advantage and, although tailored treatments might be appropriate for selected patients, the one-size-fits-all approach is still widely used in chemo-refractory patients. Currently, different antiangiogenics and multitarget agents are indicated in treatment of metastatic CRC (mCRC) whereas the identification of useful predictive factors for the treatment response is lacking. Analysis of potential predictive biomarkers of efficacy of regorafenib is still ongoing but may prove to be difficult because of its nonspecific activity across a wide range of angiogenic, oncogenic, stromal, and intracellular signaling kinases. We present a case of a 57-year-old Caucasian woman diagnosed with recurrence after curative surgery for rectal adenocarcinoma stage III (ypT3N2). Despite undergoing multiple lines of standard chemotherapy, disease control could not be maintained. Consequently, regorafenib, a multikinase inhibitor with antiangiogenic proprieties, was started as a late-line treatment and a dose reduction strategy allowed a long-term response of more than 9 years with good tolerability.

Background Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. The first-line treatment for GC is a combination of platinum and fluoropyrimidine-based therapy. Based on the positive results of RAINBOW and REGARD trials, ramucirumab either alone or in combination with paclitaxel has proved to be a safe and active option for second-line treatment in GC patients. Material and methods Advanced GC patients who received a 28-day cycles of ramucirumab and paclitaxel until disease progression or unacceptable toxicity were evaluated. Eligible patients had ECOG PS ≤ 1 and adequate organ function. Baseline characteristics were assessed for progression-free survival (PFS) and overall survival (OS). The Kaplan–Meier method and Cox proportional-hazards regression models were used for survival analyses. Results In our single institution experience, we included a total of 67 patients. A median OS of 8 months and a median PFS of 4 months, were recorded. In patients experiencing an initial partial response (PR), we observed a significant association between tumor response and survival outcomes (OS and PFS). The OS and PFS were 15 and 11 months in patients who experienced PR compared to 8 and 4 months in patients without PR (p = 0.02; p = 0.04). Conclusion Treatment with ramucirumab plus paclitaxel yielded the highest overall response rate reported to date for patients with previously treated advanced GC. In our experience, the initial tumor response is associated with a greater survival benefit which could be further improved by the identification of biomarkers predicting response.

e23520 Background: In adult GISTs are frequently sporadic, while rarely GISTs are linked to Carney Triad and Carney-Stratakis Syndrome and NF1. GISTs with second primary tumors are reported in 4-33% of patients in literature and genetic counseling is suggested to explore an underlying germline mutations pathway. Methods: In our Academic Hospital Centre (EURACAN member) in Florence, Italy, we are following patients with GIST and multiple primary tumors with genetic counseling (72 GISTs with second tumors/185 patients with GIST) and germline analysis of the following genetic panel is performed as clinically indicated: BRCA1, BRCA2, MUTYH, MLH1, MSH2, MSH6, CDH1, ATM, TP53, PTEN, CHECK2, PALB2, BARD1, BRIP1, BLM, RAD51C, RAD51D, XRCC2, PMS2, MRE11A, RAD50, NBN, FAM175A, EPKAM, TSK1, MEN1 by sequencing analysis with Illumina MiSeq by kit multiplicom BRCA Hereditary cancer Mastr plus, and bioinformatic analysis by software SOPHIADDM (Sophia genetics) for point genetic alterations of BRCA1 NM_007294.3, BRCA2 NM_000059.3, MUTYH NM_000249, MSH2 NM_000251, MSH6 NM_000179, CDH1 NM_00444360, ATM NM_000051, TP53 NM_000546, PTEN NM_000314, CHEK2 NM_001005735, PALB2 NM_024675, BARD1 NM_000465, BRIP1 NM_032043, BLM NM_000057, RAD51C NM_002876, RAD51D NM_001142571, XRCC2 NM_005431, PMS2 NM_000535, MRE11A NM_005590, RAD50 NM_006732, NBN NM_002485, FAM175A NM_139076, EPCAM NM_002354, STK1 NM_000455, MEN1 NM_000244 and MLPA (Multiplex Ligation-dependent Probe Amplification) test analysis for patients with kit P087-BRCA1,P045-BRCA2(CHEK2, P248-MLH1-MSH2, P003-MLH1/MSH2, P072-MSH6-MUTYH (MRC-Holland). Results: In 3 patients germline mutations have been observed: 1 patient showed the c.1192dupG, p.(Ala398Glyfs*19) pathogenic mutation in exon 7 of MSH2 gene, confirmed by Sanger Sequencing, 1 patient showed c.565-?_1130+?del mutation consisting in heterozygous 3-4-5-6 exons deletion of MSH2 gene, confirmed by MLPA analysis, and in 1 patient the following ATM alteration has been identified in heterozygosis: ATM c.5319+2T > C, p.(?). In the 2 patients with Lynch syndrome with colon adenocarcinoma (MSI-H), synchronous GISTs (1 patient quadruple WT and 1 patient kit ex 11 mutated ) were diagnosed; in the patient with ATM mutation, the diagnosis of GIST (kit ex 11 mutated) occurred after prostate adenocarcinoma and before colon adenocarcinoma (MSI-H). Conclusions: Our analysis suggests that GIST diagnosis could be tumor-related to multiple hereditary tumor syndromes as Lynch Syndrome and Ataxia-Teleangectasia syndrome, the latter being linked in eterozygosis to tumor susceptibility to breast in female. This report represents a high value in terms of genetic counseling for relatives and in terms of therapeutic implications for the patients.