Background: Tumor microenvironment (TME) is a pitch for multiple players, where the crosstalk between tumor and immune cells determines the fate of tumor progression. In fact, immune system may either destroy or paradoxically promote cancer growth, by recruiting immunosuppressive and inflammatory cells. MLR and LDH levels could be dynamic biomarkers that provide indirect information about TME and are associated with poor prognosis in many tumors. Therefore, we evaluated their prognostic impact in mCRC pts. Methods: We conducted a retrospective cohort study evaluating consecutive data of 165 mCRC pts treated in 2004-2017 at the Unit of Medical Oncology and Oncology Prevention, CRO of Aviano. The prognostic impact of MLR and LDH levels on overall survival (OS) was analyzed through uni- and multivariate Cox regression analysis. Results: At median follow-up of 61.87 months, median OS was 30.74 months. Overall, 100 pts (62%) were aged <65, 63 pts (39%) had a left tumor, 9 (6%) had a BRAF mutation and 45 (28%) had a KRAS mutation, underestimated for the missing data. High levels of LDH (>480 U/L) and MLR (>0.44) were discovered in 35 (21%) and 40 pts (24%), respectively. By univariate analysis, resection (HR 0.25, P < 0.001, 95% CI 0.14-0.45), metastasectomy (HR 0.46, P < 0.001, 95%CI 0.30-0.70) and sidness (left tumors: HR 0.58, P = 0.035, 95%CI 0.36-0.96) were associated with better OS. Conversely, older age (HR 1.63, P = 0.014, 95%CI 1.10-2.42), KRAS mutation (HR 1.77, P = 0.017, 95%CI 1.19-2.85), LDH or MLR high (HR 2.92, P < 0.001, 95% CI 1.77-4.79) or both (HR 4.02, P < 0.001, 95%CI 1.93-8.37) were associated with worse OS. By multivariate analysis, metastasectomy (HR 0.53, P = 0.04, 95%CI 0.29-0.97), KRAS mutation (2.10, P = 0.014, 95% CI 1.16-3.79), LDH or MLR high (HR 3.05, P < 0.001, 95%CI 1.68-5.55) or both (HR 2.65, P = 0.039, 95%CI 1.05-6.68) confirmed their impact on OS. Interestingly, high MLR was associated with right and rectum tumors P = 0.007). Conclusions: We showed that high baseline LDH, MLR or both are poor prognostic factors in mCRC pts adding further evidence of the interlink between immune system, inflammation and cancer. However, further prospective and translational studies are needed to better deepen this topic. Legal entity responsible for the study: CRO, IRCCS, National Cancer Institute of Aviano. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
In the last few years, significant advances in molecular biology have provided new therapeutic options for colorectal cancer (CRC). The development of new drugs that target the immune response to cancer cells seems very promising and has already been established for other tumor types. In particular, the use of immune checkpoint inhibitors seems to be an encouraging immunotherapeutic strategy. Areas covered: In this review, the authors provide an update of the current evidence related to this topic, though most immunotherapies are still in early-phase clinical trials for CRC. To understand the key role of immunotherapy in CRC, the authors discuss the delicate balance between immune-stimulating and immune-suppressive networks that occur in the tumor microenvironment. Expert opinion: Modulation of the immune system through checkpoint inhibition is an emerging approach in CRC therapy. Nevertheless, selection criteria that could enable the identification of patients who may benefit from these agents are necessary. Furthermore, potential prognostic and predictive immune biomarkers based on immune and molecular classifications have been proposed. As expected, additional studies are required to develop biomarkers, effective therapeutic strategies and novel combinations to overcome immune escape resistance and enhance effector response.
e21632 Background: It is estimated that about half of cancer patients (pts) use at least one form of (CAM) Complementary and Alternative Medicine in their life but there is a strong reticence of pts in talking about CAM with their oncologist. Aim of this study is to inform pts about CAM. Methods:From April to December 2016, the observational pilot trial “CAMEO-PRO” prospectively enrolled 200 cancer pts that were invited to attend a tutorial about CAM at the Department of Oncology, University Hospital of Udine (Italy). Before and after the seminar, pts were asked to fill a questionnaire reporting their knowledge and opinion about CAM . Results:Median age was 61 years, 141 (72%) women and 53 (28%) men. At study entry, 139 (72%) pts declared they have never been interested in this topic before; 22 pts (12%) revealed the use of a type of alternative therapy and 53 (31%) revealed the use of complementary therapy. Overall, 111 (55.5%) pts participated to the tutorial. Table 1 shows the percentage of response and the opinion’s change about CAM before and after the tutorial. Conclusions:Informative seminars seem to have an impact on patients’ perceptions and opinions about CAM. [Table: see text]
// Valentina Fanotto 1,* , Elena Ongaro 1,* , Karim Rihawi 2 , Antonio Avallone 3 , Nicola Silvestris 4 , Lorenzo Fornaro 5 , Enrico Vasile 5 , Lorenzo Antonuzzo 6 , Francesco Leone 7 , Gerardo Rosati 8 , Francesco Giuliani 4 , Roberto Bordonaro 9 , Mario Scartozzi 10 , Giovanna De Maglio 11 , Francesca V. Negri 12 , Gianpiero Fasola 1 and Giuseppe Aprile 1 1 Department of Oncology, University and General Hospital, Udine, Italy 2 Department of Oncology, S.Orsola-Malpighi Hospital, Bologna, Italy 3 Gastrointestinal Medical Oncology Unit, National Cancer Institute "Fondazione Giovanni Pascale"-IRCCS, Napoli, Italy 4 Department of Oncology, National CancerInstitute "Giovanni Paolo II"-IRCSS, Bari, Italy 5 Unit of Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy 6 Department of Oncology, Careggi Hospital, Firenze, Italy 7 Department of Medical Oncology, University of Torino, Candiolo Cancer Institute-FPO-IRCCS, Torino, Italy 8 Medical Oncology Unit, San Carlo Hospital, Potenza, Italy 9 Department of Oncology, ARNAS Garibaldi, Catania, Italy 10 Department of Oncology, University Hospital, Cagliari, Italy 11 Department of Pathology, University and General Hospital, Udine, Italy 12 Medical Oncology Unit, University Hospital, Parma, Italy * These authors have contributed equally to this work Correspondence to: Giuseppe Aprile, email: // Keywords : gastric cancer, colorectal cancer, HER2-inhibition, prognosis, predictive factor Received : December 11, 2015 Accepted : June 16, 2016 Published : August 12, 2016 Abstract HER-2 (ErbB-2, c-erbB2 or Her2/neu), a member of the HER-family, is directly involved in the pathogenesis and progression of several human cancers; as such, it is also often considered as a poor prognostic factor. Following the revolutionary impact of anti-HER-2 therapy in breast cancer patients, the role of HER-2 and its blockade has also been extensively evaluated in other tumor types, including gastric and colorectal adenocarcinoma. The aims of this review are to recall the important results achieved with the use of HER-2 inhibitors in both gastric and colorectal cancer, and to discuss on the updates available on the role of HER-2 as prognostic and predictive factor in these malignancies.
