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Objectives Two issues were put forth by clinicians in the management of the advanced stages of rare variants of pancreatic ductal adenocarcinoma and other exocrine histotypes with peculiar clinical and pathological features: Do chemotherapy regimens recommended in pancreatic ductal adenocarcinoma patients have a clinical activity in rare pancreatic tumors? Or should other chemotherapy combinations be considered in this subset of patients? Methods We conducted a multicenter retrospective study that collected data from 2005 to 2016 at 14 Italian cancer centers with the aim to evaluate tumor response and time to progression for first- and second-line and overall survival. Results Of approximately 4300 exocrine pancreatic cancer patients, 79 advanced cases affected by rare histological types were identified, with pancreatic acinar cell cancer (n = 23), pancreatic adenosquamous cancer (n = 16), and mucinous cystic neoplasm with an associated invasive mucinous cystadenocarcinoma (n = 15) most represented. Survival analyses for each subgroup in relation with the different chemotherapy regimens showed the lack of statistical significance correlations. Conclusions Because of the lack of clinical trials in patients affected by these rare pancreatic histotypes, only their molecular classification would help clinicians in future therapeutic choice.

5-Fluorouracil is among the most widely used anticancer drug, but a fraction of treated patients develop severe toxicity, with potentially lethal injuries. The predictive power of the available pretreatment assays, used to identify patients at risk of severe toxicity, needs improvements. This study aimed to correlate a phenotypic marker of 5-fluorouracil metabolism (the individual degradation rate of 5-fluorouracil-5-FUDR) with 15 functional polymorphisms in the dihydropyrimidine dehydrogenase gene (DPYD). Single SNP (single-nucleotide polymorphism) analysis revealed that the SNPs rs1801160, rs1801265, rs2297595 and rs3918290 (splice site variant IVS14+1G>A) were significantly associated with a decreased value of 5-FUDR, and the rs3918290 causing the larger decrease. Multi-SNP analysis showed that a three-SNP haplotype (Hap7) involving rs1801160, rs1801265 and rs2297595 causes a marked decrease in 5-FUDR, comparable to that caused by the splice site variant rs3918290, which is the main pharmacogenetic marker associated with severe fluorouracil toxicity. The similar effect played by Hap7 and by the splice site variant rs3918290 upon individual 5-FUDR suggests that Hap7 could also represent a similar determinant of fluorouracil toxicity. Haplotype assessment could improve the predictive value of DPYD genetic markers aimed at the pre-emptive identification of patients at risk of severe 5-fluorouracil toxicity.The Pharmacogenomics Journal advance online publication, 28 July 2015; doi:10.1038/tpj.2015.56.

// Federica Mazzuca 1, 2 , Concetta Elisa Onesti 1, 3 , Michela Roberto 1, 2 , Marco Di Girolamo 4 , Andrea Botticelli 1 , Paola Begini 5 , Lidia Strigari 6 , Paolo Marchetti 1, 2 and Maurizio Muscaritoli 7 1 Department of Clinical and Molecular Medicine, “Sapienza” University of Rome, Rome, Italy 2 Department of Medical Oncology, Sant’Andrea Hospital, Rome, Italy 3 Department of Medical Oncology, University Hospital (CHU) and University of Liege, Liege, Belgium 4 Department of Radiology, Sant’Andrea Hospital, Rome, Italy 5 Department of Gastroenterology, Sant’Andrea Hospital, Rome, Italy 6 Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome, Italy 7 Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy Correspondence to: Concetta Elisa Onesti, email: elisaonesti@gmail.com Keywords: breast cancer; sarcopenia; lean body mass; anthracyclines toxicity; adjuvant chemotherapy Received: February 12, 2018 Accepted: April 28, 2018 Published: May 22, 2018 ABSTRACT Background: Sarcopenia refers to the reduction of both volume and number of skeletal muscle fibers. Lean body mass loss is associated with survival, quality of life and tolerance to treatment in cancer patients. The aim of our study is to analyse the association between toxicities and sarcopenia in early breast cancer patients receiving adjuvant treatment. Materials and Methods: Breast cancer patients who have received anthracycline-based adjuvant treatment were retrospectively enrolled. CT scan images performed before, during and after adjuvant chemotherapy were used to evaluate lean body mass at third lumbar vertebra level with the software Slice Omatic V 5.0. Results: 21 stage I–III breast cancer patients were enrolled. According to the skeletal muscle index at third lumbar vertebra cut-off ≤38.5 cm 2 /m 2 , 8 patients (38.1%) were classified as sarcopenic before starting treatment, while 10 patients (47.6%) were sarcopenic at the end of treatment. A lower baseline L3 skeletal muscle index is associated with G3-4 vs G0-2 toxicities (33.4 cm 2 /m 2 (31.1–39.9) vs 40.5 cm 2 /m 2 (33.4–52.0), p = 0.028). Similarly skeletal muscle cross sectional area was significantly lower in patients with G3-4 toxicities (86.7 cm 2 (82.6–104.7) vs 109.0 cm 2 (83.3–143.9), p = 0.017). L3 skeletal muscle index is an independent predictor of severe toxicity ( p = 0.0282) in multivariate analysis. Conclusion: Lean body mass loss is associated with higher grade of toxicity in early breast cancer patients receiving adjuvant chemotherapy.

TPS10129Background: Malnutrition and sarcopenia may arise in both colorectal and breast cancer since the first visit. Previous studies demonstrate that malnourished cancer patients have a decreased...

Background: The aim of the study was to assess the association of single nucleotide polymorphisms (SNPs) C677T and A1298C in the methylenetetrahydrofolate reductase gene with colorectal, esophageal/gastric and pancreatic cancer in a cohort of Italian patients. Methods: A total of 790 cancer patients and 202 healthy controls were genotyped and distributions in genotype and allele frequencies were compared by Chi-squared analysis and logistic regression analysis. Results: According to most of previous findings, we found an effect of the C677T variant, but no effect of the A1298C, in colorectal and esophageal/gastric, whereas no association was evidenced with pancreatic cancer. We found that only homozygous TT carriers of the C677T variant had an increased risk for onset of cancer. Conclusion: This result could be related to dietary and behavioral habits of the analyzed population, which could mitigate the deleterious effect of the T allele in heterozygosity and it highlights the importance to validate genetic determinant of cancer risk in different population and geographical areas. World J Oncol. 2015;6(4):394-397 doi: http://dx.doi.org/10.14740/wjon930w

ROS1+ patients represent a unique molecular subset of non-small cell lung cancer (NSCLC). Early phase clinical trials have shown a high response rate to crizotinib in these patients. We describe a case of an 18 years old woman, never smoker, with NSCLC ROS1+ and miliary brain metastases treated with crizotinib and radiotherapy. From October 2014 to June 2015 the Patient was treated with crizotinib. The first intracranial time to progression (IT-TTP) occurred after 7 months; the patient underwent stereotactic radiosurgery (SRS) and continued TKI treatment. The second IT-TTP appeared after 16 months. A continued response in the chest was observed for all the 23 months of crizotinib treatment. At the progression, we assessed programmed death ligand 1 (PD-L1) expression by immunohistochemistry, that resulted highly expressed. Our report indicates that the integration of crizotinib with local treatments should be considered in ROS1 NSCLC patients experiencing oligometastatic progression. Moreover, this case is an example of PD-L1 strong in oncogene addicted patients.

Background/Aims The prognosis of pancreatic adenocarcinoma (PAC) is poor. The serum carbohydrate antigen 19-9 (CA 19-9) level has been identified as a prognostic indicator of recurrence and reduced overall survival. The aim of this study was to identify preoperative prognostic factors and to create a prognostic model able to assess the early recurrence risk for patients with resectable PAC. Methods A series of 177 patients with PAC treated surgically at the St. Andrea Hospital of Rome between January 2003 and December 2011 were reviewed retrospectively. Univariate and multivariate analyses were utilized to identify preoperative prognostic indicators. Results A preoperative CA 19-9 level >228 U/mL, tumor size >3.1 cm, and the presence of pathological preoperative lymph nodes statistically correlated with early recurrence. Together, these three factors predicted the possibility of an early recurrence with 90.4% accuracy. The combination of these three preoperative conditions was identified as an independent parameter for early recurrence based on multivariate analysis (p=0.0314; hazard ratio, 3.9811; 95% confidence interval, 1.1745 to 15.3245). Conclusions PAC patient candidates for surgical resection should undergo an assessment of early recurrence risk to avoid unnecessary and ineffective resection and to identify patients for whom palliative or alternative treatment may be the treatment of choice.

e14506 Background: RCC is considered a highly immunogenic tumor responding to anti-angiogenetic TKI and immunotherapy. A better understanding of the functions of immune cells in RCC, the immune-modulatory effects of TKIs treatment as well as defining patients most likely to benefit to the different therapies will be crucial to optimize combined or sequential immunotherapeutic approaches in RCC patients. Methods: Monocyte derived Dendritic Cells (DCs) from 10 healthy donors were differentiated in presence of Pazopanib and Sunitinib used at plasmatic equivalent concentration (Sigma-Aldricht). At the end of the culture, DCs were characterized for marker expression, endocytosis, signal transduction and microvesicle release. Similarly, DCs derived from RCC patients were analyzed together with circulating T cells before and during TKI treatments. Results: Pazopanib and Sunitinib differently affect DC differentiation. Pazopanib, but not Sunitinib, strongly improves DC performance as antigen-presenting cells, promoting the upregulation of the maturation markers HLA-DR (+1,5 fold increase compared to Sunitinib-treated DCs), CD40 (+3 fold increase) and CCR7 (+2 fold increase) a decrease in phagocytosis and the inhibition of pERK1/2 signaling. 99% of Sunitinib-DCs expressed PD-L1 vs 80% Pazopanib-DCs , with a higher expression of the receptor as indicated by mean fluoresce intensity (MFI fold increase of +2,1). Similar results were obtained analyzing shedded microvesicles. Results were confirmed in DCs differentiated from RCC patients during Pazopanib treatment (before and at 30 and 60 days) and suggest a reverse of the tumor induced immunosuppression. Moreover, only Pazopanib treatment appears to induce in these patients a defined circulating CD4+ T cell population highly expressing CD137 molecule (%CD4+CD137+: T0:0,3; T30: 4,7; T60:29,4). Conclusions: TKIs can affect immunity in RCC patients. In particular, Pazopanib appears to function as a potent activator of DCs in vitro and in vivo associated with the neo-activation of a CD137+ T cell population. These results can guide for designing novel protocols to combine TKIs with immunoregulatory receptors targeting in RCC.

Triple negative breast cancer (TNBC) has an aggressive clinical behaviour, with a poorer prognosis compared to other subtypes. Recently, tumor-infiltrating lymphocytes (TILs) have been proposed as a predictive biomarker for a better clinical outcome and pathological response (pR) after neoadjuvant chemotherapy (NACT) in TNBC. These data confirm the role of the immune system in the neoplastic progression and in the response to therapy. We performed a retrospective analysis of 54 pre-NACT biopsies of TNBC and compared both the percentage of stromal TILs and the degree of PD-L1 expression with the extent of pR to standard NACT. A pathological complete response (pCR) was achieved in 35% of cases. Univariate analysis showed (i) a significant association between PD-L1 expression in ≥25% of neoplastic cells and the achievement of a pCR (p=0.024); (ii) a significantly higher frequency of pCR in cases showing ≥50% stromal TILs (p<0.001). However in the multivariate analysis only PD-L1 expression on tumor cells remained significantly associated with pCR (OR = 1,13; 95% CI 1,01–1,27), suggesting that the expression of this biomarker could be associated with a subpopulation of TNBC more likely to respond to chemotherapy. These data need to be confirmed by larger studies.

// Marina Borro 1,2 , Andrea Botticelli 3 , Federica Mazzuca 3 , Elisa Concetta Onesti 3 , Giovanna Gentile 1,2 , Adriana Romiti 3 , Bruna Cerbelli 4 , Eva Mazzotti 3 , Luca Marchetti 5 , Luana Lionetto 2 , Maurizio Simmaco 1,2 and Paolo Marchetti 2,3 1 Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), “Sapienza” University of Rome, Rome, Italy 2 Advanced Molecular Diagnostic, IDI-IRCCS, Rome, Italy 3 Department of Clinical and Molecular Medicine, “Sapienza” University of Rome, Rome, Italy 4 Department of Radiological Oncological and Pathological Sciences, “Sapienza” University of Rome, Rome, Italy 5 Department of Clinical Oncology, “Sapienza” University of Rome, Rome, Italy Correspondence to: Andrea Botticelli, email: // Keywords : 5-FU degradation rate, phenotypic test, 5-FU toxicity, gastro-esophageal cancer, DPYD Received : August 16, 2016 Accepted : October 05, 2016 Published : October 11, 2016 Abstract Background: 5-fluorouracil (5-FU) based chemotherapy is the most common first line regimen used in gastric and gastroesophageal junction cancer , but development of severe toxicity is a main concern in the treatment. The present study is aimed to evaluate a novel pre-treatment assay, known as the 5-FU degradation rate (5-FUDR), as a predictive factor for 5-FU toxicity. Methods: Pre-treatment 5-FUDR and gene polymorphisms related to 5-FU metabolism ( DPYD IVS14+1G>A, MTHFR A1298T or C677T, TMYS TSER) were characterized in gastro-esophageal cancer patients. Association with toxicities was retrospectively evaluated, using multivariate logistic regression analysis. Results: 107 gastro-esophageal cancer patients were retrospectively analyzed. No relation between gene polymorphisms and toxicity were detected, while low ( 95 th centile) 5-FUDRs were associated with development of grade 3-4 toxicity (OR 11.14, 95% CI 1.09-113.77 and OR 9.63, 95% CI 1.70-54.55, p = 0.002). Conclusions: Compared to currently used genetic tests, the pre-treatment 5-FUDR seems useful in identifying patients at risk of developing toxicity.

On account of the lack of predictive biomarkers of toxicity, we investigated whether polymorphisms of genes involved in fluoropyrimidine metabolism and 5-fluorouracil (5-FU) degradation rate were associated with outcomes of adjuvant capecitabine in patients with early stage gastrointestinal cancers. Genotyping of DPYD GIVS14A, MTHFR C677T and A1298C SNPs were performed by pyro-sequencing technology. PCR analysis was used for genotyping TYMS-TSER. We also evaluated the 5-FU degradation rate, which determines the amount of drug consumed by PBMC in a time unit. Association of these variables with clinical outcome was evaluated using multivariate logistic regression analysis. One hundred forty-two patients with early stage colon (39%), rectal (28%), stomach (20%) and pancreatic (13%) cancer, treated with adjuvant capecitabine, were included in this retrospective analysis. Seventy and 20% of the patients suffered from at least one G1–4 and G3–4 adverse events, respectively. According to the 5-FU degradation rate, three and 13 patients were assigned as poor ( 2.1 ng/mL/106 cells/min) metabolizers, respectively. At a multivariate logistic regression analysis, an altered 5-FU degradation rate (values 2.10 ng/mL/106 cells/min) was associated with grade 3–4 adverse events (OR = 2.09, 95% CI: 1.14–3.82, P = 0.01). No correlation was reported between toxicity and gene polymorphisms except for hand–foot syndrome that was more frequent in the MTHFR 1298CC homozygous variant genotype (OR = 2.03, 95% CI 1.04–3.96, P = 0.03). 5-FU degradation rate may be regarded as possible predictive biomarker of capecitabine toxicity in early stage gastrointestinal cancer.

Background: Immune checkpoint inhibitors have revolutionized treatment and outcome of severe and often fatal disease, as metastatic lung cancer, demonstrating long-term tumor control and extended patient survival. Unfortunately, only 25-30% of patients have a long-term benefit from immunotherapy, while the remaining 70-75% demonstrate primary or acquired resistance. Recently, indoleamine 2,3-dioxygenase (IDO) has been proposed as a possible mechanism of resistance to anti-PD1 treatment. Indeed, IDO catalyzes the degradation of tryptophan (Trp) into kynurenine (Kyn), which seems to enhance the activity of Treg, leading to an immunosuppressive microenvironment. Methods: The serum concentrations of Trp and Kyn were measured by high-performance liquid chromatography tandem mass spectrometry in 26 patients affected by non-small cell lung cancer (NCLSC) before the start of the second-line therapy with nivolumab. The IDO activity was expressed with Kyn/Trp ratio. The associations between Kyn/Trip ratio and early progression, PS, age, sex, brain metastases and pleural effusion were analyzed using Spearman test and Mann Whitney test. Results: 14 out of 26 patients (54%) presented early progression (defined as progression of the disease within 6 months from the beginning of nivolumab treatment). The median value of Kyn/Trp ratio was 0.073 (0.024-0.18). We found a significant association between Kyn/Trp ratio and early progression (p= 0.009), while no statistical associations were found between Kyn/Trp ratio and PS, age, sex, brain metastases and pleural effusion. Indeed, patients with early progressive disease presented a median value of Kyn/Trp ratio significantly higher than other patients (0.094 vs 0.052; p= 0.01). Conclusion: The pretreatment evaluation of IDO activity, expressed as Kyn/Trp ratio, seems to be associated with response to immunotherapy. In particular, higher Kyn/Trp ratio could predict resistance to anti-PD-1 treatment. These preliminary results suggest the possibility of using anti-PD-1 plus IDO inhibitor in patients with high level of Kyn/Trp ratio. Citation Format: Andrea Botticelli, Bruna Cerbelli, Luana Lionetto, Ilaria Zizzari, Annalina Pisano, Michela Roberto, Elisa Onesti, Francesca Romana DI Pietro, Chiara Napoletano, Laura Pizzuti, Patrizia Vici, Giulia D'Amati, Federica Mazzuca, Maurizio Simmaco, Marianna Nuti, Paolo Marchetti. The key role of kynurenine in anti-PD-1 failure [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5705.

e15021Background: Immune checkpoint inhibitors have revolutionized treatment and outcome of NSCLC. Unfortunately, only 25-30% of patients have a long-term benefit, while the remaining 70-75% demons...

e15020Background: Immune Checkpoint Inhibitors (ICIs) are improving the survival of cancer patients, however only the 20-30% of treated patients present long term benefits. Hence in the context of ...

Third-generation aromatase inhibitors (AI) are potent suppressors of aromatase activity. The aim of this study was to measure the incidence of adverse effects in breast cancer patients treated with AI-based adjuvant therapy and the relationship with the CYP19A1 genotypes.Forty-five postmenopausal breast cancer patients (46-85 yrs) in AI adjuvant treatment were genotyped for the rs4646 polymorphisms of CYP19A1 gene and three variations were identified. Toxicities were registered at each follow-up medical examination, and classified in accord with the Common Terminology Criteria for Adverse Events.Twenty-four (53.3%) patients presented the GG genotype; 19 (42.2%) the GT, and 2 (4.4%) the TT. The AI treatment was Anastrazole for 35 patients (77.8%) and Letrozole for the others (n=10; 22.2%). Osteoporosis was significantly associated with the GG genotype (p=0.001). Treatment discontinuation (TD) was observed in 6 cases (13.3%). The only parameter able to predict TD was the appearance of severe arthralgia/myalgia (Odds Ratio, OR=23.75; p=0.009), when adjusted for age and AI treatment.Our results suggest that CYP19A1 polymorphic variants may influence susceptibility to develop AI-related side effects. Further prospective studies are needed to confirm the role of the aromatase gene (CYP19A1) polymorphisms in predicting adverse effects to AI-based therapy.Üçüncü jenerasyon aromataz inhibitörleri (Aİ) aromataz aktivitesinin potent supresörleridir. Bu çalışmanın amacı Aİ bazlı adjuvan terapi ile tedavi edilen meme kanserli hastalarda advers etkilerin insidansını ve CYP19A1 genotipleri ile ilişkisini belirlemekti.Aİ adjuvan tedavisindeki 45 postmenopozal meme kanserli hasta (46–85 yaş) CYP19A1 geninin RS4646 polimorfizmleri için genotiplendirildi ve üç varyasyon tanımlandı. Toksisiteler her takipteki tıbbi muayenede kaydedildi ve Advers Olaylar için Ortak Terminoloji Kriterleri ile uyumlu olarak sınıflandırıldı.Yirmi dört (%53,3) hasta GG, 19’u (%42,2) GT ve 2’si (%4,4) TT genotipi gösterdi. Aİ tedavisi 35 hasta (%77,8) için Anastrozol ve diğerleri (n=10; %22,2) için Letrozol idi. Osteoporoz, GG genotipi ile anlamlı olarak ilişkiliydi (p=0,001). Tedaviye devam etmeme (TD) 6 olguda (%13,3) görüldü. Yaşa ve Aİ tedavisine göre düzeltildiğinde, TD’yi öngörebilecek tek parametre şiddetli artralji/miyalji oluşumu idi (Odds Oranı, OR=23,75; p=0,009).Bulgularımız CYP19A1 polimorfik varyantların Aİ ile ilişkili yan etkiler geliştirme duyarlılığını etkileyebileceğini düşündürmektedir. Aİ bazlı terapilerin advers etkilerini öngörmede aromataz gen (CYP19A1) polimorfizminin rolünü doğrulamak için ileri prospektif çalışmalara ihtiyaç vardır.

The purpose of this study was to examine the longitudinal relationship between Positivity (POS), defined as a stable disposition to view at experience under a positive outlook, and physical and psychological functioning in a sample of cancer patients immediately after diagnosis and one year later.A total of 110 patients (40% males) with pulmonary, colorectal and breast cancer, aged 30-75 (M age = 59.62; SD = 10.33), have been prospectively enrolled between 2012 and 2013, at the S. Andrea Hospital in Rome. All patients were previously aware of their diagnosis. A follow-up one year after diagnosis was conducted. We used structural equation modeling in order to analyse the specific effects of POS on functioning impairment from diagnosis to follow up.POS was associated with less functioning impairment both at diagnosis and follow-up assessments. Furthermore, POS level at diagnosis continued to be associated with less functioning impairment one year later, after controlling for its stability.Patients with higher level of POS tended to report less symptoms associated with negative affect such as anxiety and despondency and to preserve their habitual relationships and social roles. POS may act as a basic disposition that sustains patients' efforts to deal efficaciously with severe illness, by complying with medical treatment and using cognitive strategies that enable individuals to cope with concurrent and prospective challenges of illness.

700 Background: The standard of care for locally advanced rectal cancer (RC) is neoadjuvant chemoradiotherapy (CRT) with 5FU aimed to tumor downstaging prior to radical resection but there is a wide spectrum of responses to it, from none to complete. The aim of this project is to validate top candidate genes previously identified by microarray studies as prognostic and predictive classifiers of locally advanced RC, using the NanoString nCounter Platform. Methods: Two cohorts of RC patients were identified according to tumor regression grade (TRG) of AJCC Staging Manual (7th) system: 1) good prognosis: patients that after neoadjuvant CRT obtained TRG0 (complete response); 2) poor prognosis: patients with TRG1 (moderate response), patients with TRG2 (minimum response rate) and patients with TRG3 (poor response). Pre-treatment biopsies tissues from ten TRG0 patients (ID TRG0bio) and thirteen TRG1-3 patients (ID TRG1-3bio) were macro-dissected from FFPE sections, RNA isolated and used for expression profiling of a 305 genes custom code set consisting of 12 normalizer genes, 101 prognostic genes (markers of stemness, invasiveness, proliferation, drug-resistance), 192 predictive genes (involved in response to 5-FU, to radiation therapy and in the response to CRT). All samples were normalized using the geometric mean of the housekeeper genes. P-values were calculated by student’s t-test and was consider significance if was less than 0.05. Gene-specific RNA expression profiles were compared using Spearman's correlation. The heat map was generated using MeV 4.9.0. Results: When we compared TRG0bio to TRG1-3bio tissues, among the 305 genes assayed, changes in expression levels of 18 genes (SSB, GAPDH, TXNDC9, DUT, PKM, STAT1,SLC28A3, DAG1, TYMS, FERMT1, ARNT,SLC6A6, SMAD3, SCRN1, POU5F1, GNG4, PDRG1, ATP5E) were statistically significant. Conclusions: Results suggest that TRG0 RC is characterized by distinct molecular events compared TRG1-3 disease. Next steps will be: to amplify sample size, to understand signaling pathways of top differentially expressed genes and to validate prospectively our gene signature.

Rationale:Regorafenib is the new standard third-line therapy in metastatic colorectal cancer (mCRC). However, the reported 1-year overall survival rate does not exceed 25%.Patient concerns:A 55-year-old man affected by mCRC, treated with regorafenib combined with stereotactic body radiothera

e15588 Background: Chemotherapy (CT) and chemoradiotherapy (CTRT) both in neoadjuvant (neoadj) or adjuvant (adj) setting are associated with better overall survival (OS) over surgery alone in patients (pts) with resectable gastroesophageal (GE) adenocarcinoma (ADK). The best sequence and timing of treatments have still not been defined. A large cohort of GE ADKs derived from 2 high-volume Italian centers was analyzed to describe clinical outcomes and prognostic factors. Methods: 497 patients (pts) diagnosed with GE ADK who underwent surgery with curative intent from 2007 to 2016 were considered. Variables analyzed were: age, sex, tumor location, histology, T, N, M, R, G, HER-2, Helicobacter Pylori (HP) infection, (neo)adj CT, and adj CTRT. Analysis was performed according to ITT principle. Results: Median age at diagnosis was 71 years (range 35-92). At 26.7 months (mo) median follow-up, median OS was 27.6 mo (range 1-127) and median time to recurrence (TTR) 10.8 mo (range 7.8-13.1). Adj CT was administered in 203 cases (41%); 116 pts (23%) had adj CTRT and 47 (9%) neoadj CT. Statistically significant variables for OS and/or TTR at 12 months at univariate analysis were: age, T, N, M, R, G, adj CTRT, neoadj CT and adj CT. Results of multivariate analysis (MVA) are shown in Table 1. Conclusions: Despite a short follow-up, our analysis performed on a very large cohort of consecutive pts confirms the prognostic value of T and N for both OS and TTR. Adj CT and CTRT had a significant impact on 1 year OS, while neoadj CT gave only a 12 months TTR significant benefit. Based on these results, perioperative treatment strategies should always be considered in the management of resectable GE cancer. [Table: see text]

Background & Aims: National Comprehensive Cancer Network (NCCN) recommends a colectomy in presence of high risk T1 colon polyps considering the risk of incomplete lymph node dissection or presence of residual disease. We evaluated the outcomes of segmental versus standard colon resection for high risk T1 colon cancers, in order to demonstrate if segmental colectomy (SegCR) allows same short-term and oncological results compared to standard radical colectomy (StaCR).Methods. A matched case-control study on patients who had undergone segmental versus standard colon resection was performed. One-hundred and two patients with high risk T1 colon cancer after endoscopic polypectomy, divided in 2 homogeneous groups of 51 cases, were analyzed, and intra-operative, post-operative and oncological data were compared.Results. Segmental colectomy allowed less operative time and intra-operative blood loss compared to StaCR (p < 0.001). Hospital stay after SegCR was shorter compared to StaCR (p < 0.001). No differences were found in terms of overall morbidity and mortality rates. Five-year actuarial overall, disease-free and disease-specific survival after StaCR were similar to SegCR (87%, 96% and 95% vs. 88%, 97% and 94%, respectively, p = 0.51, p=0.33, p=0.78).Conclusions. According to our findings, SegCR can be a valid alternative to StaCR for high risk T1 colon polyps. Segmental colectomy allows better peri-operative outcomes compared to StaCR ensuring the same oncological long-term outcomes.

Aim: 5-FU based chemotherapy is the most common regimen used for patients affected by gastric cancer both in metastatic and in adjuvant setting.Identification of predictive markers of both response and toxicity to chemotherapy is a promising approach for drug selection. The present study analyzes the predictive role of 5-FU degradation rate (5-FU-DR) and genetic polymorphisms (MTHFR, TSER, DPYD) on predicting toxicity to chemotherapy and survival Methods: 94 patients affected by gastric cancer were enrolled. Genetic polymorphisms of MTHFR, TSER and DPYD and the 5-FU-DR were analyzed. 5-FU degradation rate was determined by measuring the decrease of a fixed amount of 5-FU (10 [mu]g/mL) added to a solution of PBMC, after 2 hours incubation, expressed as nanogram per milliliter of 5-FU degraded per minute x 106 cells.Gene polymorphisms ofMTHFR, DPYD and TSER were analysed by pyrosequensing of genomic DNA extracted from peripheral blood samples. Genetic markers and the 5-FU-DR were correlated with clinical response, survival and toxicity to treatment. Results: We enrolled 94 patients with gastric adenocarcinoma. All of them received 5FU-based chemotherapy : 39 patients in metastatic setting (28 males and 11 females) and 55 in adjuvant setting (36 males and 19 females). Among the 55 patients in adjuvant setting, 44 of them developed grade 1 and 2 toxicities, while 11 patients developed grade 3 or 4 toxicities. Among the 39 patients treated for metastatic disease, 29 patients reported grade 1 or 2 toxicities while 10 reported toxicities of grade 3 and 4. We didn't found any association between polymorphisms, 5FU-DR and toxicities. We demonstrated a statistically significant association between the polymorphism of DPYD and 5FUDR (p = 0.01). In terms of survival, patients poor metabolizer with a 5-FU-DR Conclusions: 5-FU-DR and genetic polymorphisms of MTHFR and DPYD seem to be significantly involved in survival of patients undergone 5-FU based CHT for gastric cancer both in metastatic and adjuvant setting. Although, the small sample size of patients enrolled in the study, our results suggest that identification of predictive markers of toxicities and survival could help in providing a tailored treatment in patients affected by gastric cancer. Disclosure: All authors have declared no conflicts of interest.

SUMMARY Atypical bronchopulmonary carcinoid is a rare disease with poor prognosis. The low number of patients and their dispersion in different centers makes it difficult to draw clinical trials. The right treatment is still controversial. This study reports the clinical case of a patient with bronchopulmonary carcinoid, who showed stable disease with everolimus (an mTOR inhibitor) plus somatostatin analog after the failure of two lines of chemotherapy plus somatostatin analog. Although in literature the overall survival for metastatic bronchopulmonary carcinoid patients is 16 months, our patient reported a progression-free survival of 18 months with everolimus as third-line. Our case report underlines the importance to use new drugs that may change the disease course.

Well-being and mental health are not only direct functions of amount of stress, but also depend on how people appraise and face critical situations. Spiritual well-being seems to be a central component of psychological health in physically healthy individuals and it offers some protection against end-of-life despair in those with chronic diseases. In this study, 250 out and in-patients with a cancer diagnosis were interviewed with standardised instruments to measure two aspects of spirituality, existential and religious well-being, coping strategies, psychological state, and quality of life (QoL). Using multivariate logistic regression models we found that coping strategies characterized by acceptance and positive reinterpretation of the stressor, and the absence of anxiety disorder, independently increased the likelihood of the existential well-being (Odds Ratio, OR, 7.7, and OR, 4.5, respectively), whereas religious well-being was not significantly associated with these variables. Our findings show that existential and religious well-being may be very different. A spirituality-based intervention could be differently utilized by patients with different beliefs, cognitive and behaviour characteristics. Measure of coping strategies and psychological state should be part of routine management of cancer patients.

Immune Checkpoint Inhibitors (ICIs) are improving the survival of cancer patients, however only the 20-30% of treated patients present clinical benefits. Toxicity represents the major cause of reduced dosage, delayed drug administration and therapy discontinuation. Hence in the context of multiple treatment possibilities, the identification of predictive markers of response and toxicity is a challenging approach for drug selection in order to obtain the best clinical benefit while minimizing the side effects. The loss of the protective function of intestinal barriers that interacts with the environment measured as increased intestinal permeability and the changes occurring in the microbiota composition have been proposed as a mechanism potentially explaining the pathogenesis of immune related toxicity. In this review we discuss the new perspectives on the involvement of PD-1 and PDL-1 in the cross talk between gut microbiota and immune fitness and how gut microbiota impacts on the efficacy of anti-PD-1 and anti-PDL-1 treatments in cancer.