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Aim: Recommendations for managing patients with nasopharyngeal carcinoma (NPC) in non-endemic areas are largely derived from studies conducted in endemic areas. We analysed the impact of treatment approaches on survival in non-endemic areas. Methods: In an international, multicentre, retrospective study, we analyse consecutive patients with NPC diagnosed between 2004 and 2017 in 36 hospitals from 11 countries. Treatment was categorised as non-intensive (NIT), including radiotherapy alone or concomitant chemoradiotherapy (cCRT), and intensive (IT) including cCRT preceded by and/or followed by chemotherapy (CT). The impact of IT on overall survival (OS) and disease-free survival (DFS) was adjusted for all the available potential confounders. Results: Overall, 1021 and 1113 patients were eligible for overall survival (OS) and disease-free survival (DFS) analyses, respectively; 501 and 554 with Epstein Barr-encoded RNA (EBER) status available. In the whole group, 5-year OS was 84% and DFS 65%. The use of NIT was associated with a risk of death or recurrence 1.37 times higher than patients receiving IT. Patients submitted to NIT and induction CT thorn concurrent concomitant chemo and three-dimensional Conformal Radiation Therapy (3DCRT) had a risk of death or recurrence 1.5 and 1.7 times higher than patients treated with induction CT + cCRT with intensity-modulated radiotherapy (IMRT), respectively. The IT had no impact on OS in neither patients with EBER+ nor in patients with EBER-; IT showed better DFS in EBER+ but not in patients with EBER-. Conclusions: In low-incidence areas, patients with NPC treated with induction CT followed by concurrent IMRT cCRT achieved the highest DFS rate. The benefit of IT on DFS was restricted to patients with EBERthorn, suggesting that additional therapy offers no advantages in EBER- cases. (C) 2021 Elsevier Ltd. All rights reserved.

Background Distant metastases in adenoid cystic carcinoma (ACC) are common. There is no consensus on the management of metastatic disease because no therapeutic approach has demonstrated improvement in overall survival (OS) and because of prolonged life expectancy. The aim of this study is to build and validate a prognostic nomogram for metastatic ACC patients. Methods The study end-point was OS, measured from the date of first metastatic presentation to death/last follow-up. A retrospective analysis including metastatic ACC patients was performed to build the prognostic nomogram at the INT (Milan, Italy). The model was validated on an independent cohort of patients with similar characteristics treated at Leuven (Belgium). Outcome data and covariates were modelled by resorting to a random forest method. This machine-learning approach was used to guide and benchmark the subsequent use of more conventional modelling methods. Cox model performance was assessed in terms of discrimination (Harrell's c-index). Results Two hundred ninety-eight patients with metastatic ACC (testing set 259 INT, validation set 39 Leuven) were studied. Akaike Information Criterion–based backward selection yielded a 5-factor model showing a bias-corrected c-index of 0.730. Five independent prognostic factors were found: gender, disease-free interval and presence of lung, liver or bone metastases. Nomogram discrimination in the validation series was c = 0.701. Conclusion This retrospective analysis allowed the building of an externally validated prognostic nomogram. This tool might help clinicians to discriminate patients requiring prompt management from who can benefit from a ‘watchful waiting’. In addition, the nomogram might be useful to stratify patients in clinical trials.

Objectives Second-line chemotherapy in recurrent and/or metastatic head and neck cancer (r/mHNSCC) patients showed dismal results with limited tumor response and reduced life expectancy. Outside of clinical trials, data on efficacy of second line treatment after first line anti-EGFR-AB combination therapy are not available. Material and methods Data regarding r/mHNSCC consecutive pts treated with cetuximab and platinum from 2009 to 2014 at our center were retrospectively collected. The analyses of response, Progression-Free Survival (PFS) and Overall Survival (OS), each evaluated starting from first and second-line treatment, were performed. Survival curves were estimated with the Kaplan-Meier method and compared using the log-rank test. Results We identified 117 patients treated with first-line platinum and cetuximab-based therapy. Sixty-four (55%) patients did not receive second-line treatment due to worsening in performance status, 2 were not assessable for response thus 51 patients were included for analysis. Fifty-six percent were smokers/former smokers and 78% were male. Primary tumor sites were oropharynx (39%), oral cavity (31%), larynx/hypopharynx (24%) and others (6%). Regimens used in second-line were mostly monotherapies. Twenty-one % of the patients were treated within a clinical trial. Response rate (PR, CR) was 6% with 45% showing SD as best response. Median PFS was 2.2 months (95%CI:1.5–2.8 months) and OS 6.1 months (95%CI:3.7–7.2 months). Conclusions Within our single center experience only half of the patients with r/mHNSCC were able to receive second-line treatment. Response rate was unsatisfactory, but median OS seems higher than previously reported in an anti-EGFR-AB naive population (Leon 2005).

Summary Background & aims A phase III, randomized non-inferiority study was carried out to compare a two-drug combination (including nutraceuticals, i.e. antioxidants) with carnitine + celecoxib ± megestrol acetate for the treatment of cancer-related anorexia/cachexia syndrome (CACS): the primary endpoints were increase of lean body mass (LBM) and improvement of total daily physical activity. Secondary endpoint was: increase of physical performance tested by grip strength and 6-min walk test. Methods Sixty eligible patients were randomly assigned to: arm 1, l-carnitine 4 g/day + Celecoxib 300 mg/day or arm 2, l-carnitine 4 g/day + celecoxib 300 mg/day + megestrol acetate 320 mg/day, all orally. All patients received as basic treatment polyphenols 300 mg/day, lipoic acid 300 mg/day, carbocysteine 2.7 g/day, Vitamin E, A, C. Treatment duration was 4 months. Planned sample size was 60 patients. Results The results did not show a significant difference between treatment arms in both primary and secondary endpoints. Analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) increased significantly in both arms as well as physical performance assessed by 6MWT. Toxicity was quite negligible and comparable between arms. Conclusions The results of the present study showed a non-inferiority of arm 1 (two-drug combination) vs arm 2 (two-drug combination + megestrol acetate). Therefore, this simple, feasible, effective, safe, low cost with favorable cost-benefit profile, two-drug approach could be suggested in the clinical practice to implement CACS treatment.

e17054 Background: The value of plasma Epstein Barr Virus (EBV) DNA viral load in nasopharyngeal cancer (NPC) patients before treatment correlates with tumor stage and outcome in endemic areas. The aim of our analysis is to explore the role of EBV DNA in a non-endemic setting where just few experiences have been reported. Methods: The medical records of all the patients with positive EBV encoded RNA (EBER) NPC, treated in our institution from 2006 to 2014 with chemotherapy (CT) concurrent with radiation (RT), were retrospectively evaluated. Information about the known prognostic factors, as established in NPC endemic areas, were collected, as well as pretreatment plasma EBV DNA viral load, detected and quantified by real-time PCR. Results: A total of 134 patients were evaluated (median age 48 years; M:F ratio 2:1; stage II 13%, III 31%, IV 56%). Neo-adjuvant CT (TPF scheme) was administered to 78% of the patients. Platinum based CT was delivered concurrently with RT. At a median follow up of 41 months, 25...

e17073 Background: Locally advanced HPV+ oropharynx cancer (OPC) patients have a remarkable good outcome. However, the frequency of distant metastases (DM) is similar to HPV – cases. Some clinical ...

e20556 Background: To test the safety and efficacy of a combination treatment (including nutraceuticals, i.e. quercetin, alpha lipoic acid and curcumin) with carnitine + celecoxib for the treatment of cancer-related anorexia/cachexia syndrome (CACS) in the clinical practice. Primary endpoints: safety, increase of lean body mass (LBM) and improvement of quality of life. Secondary endpoints: increase of physical performance (tested by grip strength and 6-min walk test, 6MWT) and decrease of inflammation (assessed by serum levels of IL-6 and Glasgow prognostic score, GPS). Methods: Outpatients with advanced cancer at different sites with CACS (i.e. loss of body weight >5% of the pre-illness or ideal weight in the previous 3 months) were eligible to receive: L-carnitine 4 g/day + Celecoxib 300 mg/day. All patients received as basic treatment polyphenols 300 mg/day, lipoic acid 300 mg/day, carbocysteine 2.7 g/day, Vitamin E, A, C, all orally. Treatment duration was 4 months. Results: From June 2011 to April 2012, 75 patients with advanced cancer (all stage IV) at different sites were enrolled: 40 completed the treatment and were evaluable (mean age 65 ± 9.6, range 32-82 years). Results showed a significant increase of LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) from baseline as well as physical performance assessed by 6MWT. Quality of life (assessed by EORTC-QLQ-C30) as well as fatigue (assessed by MFSI-SF) also improved significantly. ECOG PS and GPS decreased significantly. The treatment was safe, no grade 3–4 toxicities occurred and no patient had to discontinue the treatment due to severe adverse events. Conclusions: The results of the present study confirm the efficacy and safety of the two-drug combination regimen previously shown in a randomized clinical trial (Madeddu et al, Clinical Nutrition 31:176-182,2012). Therefore, this simple, feasible, effective, safe, with favorable cost-benefit profile, two-drug approach could be suggested in the clinical practice as a treatment for CACS.

Background Curcumin (diferuloylmethane) is the biologically active compound of Turmeric (Curcuma Longa) and has long been used in traditional Asian medicine to treat diseases ranging from heartburn to arthritis: it is thought to have antioxidant and antinflammatory properties. Aim To assess the antioxidant and antinflammatory properties of a curcumin extract in advanced cachectic cancer patients. Methods From September 2011 to March 2012, 15 cachectic patients (M 7/F 8; age range 55–85 y) with cancer at different sites were enrolled, all stage IV. Twenty-one age/sex matched healthy controls were studied. All enrolled patients had inflammation and oxidative stress (high blood levels of proinflammatory cytokine Interleukin-6 (IL-6), high levels of blood C-reactive protein (CRP), high levels of ROS, low levels of blood antioxidant enzymes GPx and SOD and low levels of total blood antioxidant status, TAS, compared to controls. Patients were administered 4 tablets (2 g/day, equivalent to 400 mg/day of active curcuminoids extract, Meriva, Indena, Milan, Italy). Treatment duration was 4 weeks. Results A significant reduction of ROS levels ( 510 ± 120 vs 390 ± 186 Fort U)and a significant improvement of circulating levels of GPx (5630 ± 1189 vs 6590 ± 2390 U/l) as well as a significant improvement of TAS (0.61 ± 0.23 vs 0.69 ± 0.4 mmol Trolox eq.) was observed after treatment. The inflammatory marker CRP decreased significantly (38.12 ± 28.4 vs 20.24 ± 17.37 mg/dl), no significant decrease of serum IL-6 (25.58 ± 23.67 vs. 19.9 ± 16.8) was observed. No patient was withdrawn from the study and the treatment was safe and well tolerated. Conclusions Curcumin extract added to the normal diet was able to significantly improve inflammatory status and counteract key parameters of oxidative stress, such as ROS, GPx and TAS. Curcumin antinflammatory-antioxidant activity could be useful in a multi-targeted combined pharmaco-nutritional approach to treat cancer-cachexia. Dr. Roberto Serpe was supported by grant CRP1_296 from the Regione Autonoma della Sardegna by PO Sardegna FSE 2007-2013 (L.R.7/2007) titled”Promotion of scientific and technological research in Sardinia”, Italy Disclosure All authors have declared no conflicts of interest.

Aims Alterations of lipid metabolism and inflammatory parameters are frequently observed in cancer patients, especially at advanced stage, and are associated with poor prognosis; the pathogenetic mechanisms are not yet fully known and the identification of effective treatment is still far away. This study aimed to evaluate the lipid and inflammatory profile in cancer patients at diagnosis and to assess the correlation with clinical, nutritional, metabolic/functional and quality of life parameters. Methods From June 2011 to March 2012, 116 patients with a new diagnosis of cancer (breast, lung, gynecological, gastrointestinal tract) were enrolled. Plasma lipids (i.e. total cholesterol, TC; high-density lipoprotein, HDL; low-density lipoprotein cholesterol, LDL; and triglyceride,TG), indices of inflammation (i.e. erythrocyte sedimentation rate, C reactive protein [CRP], ferritin and inflammatory cytokines) and oxidative stress (reactive oxygen species, ROS; and antioxidant enzymes, SOD and GPx) were analyzed. The laboratory data obtained were correlated with clinical variables such as sex, age, ECOG PS, Glasgow prognostic score (GPS), quality of life, site and stage of disease and survival. Results Patients with advanced disease had a lower levels of fatty acids than patients at early stage. Cholesterol levels (TC, HDL and LDL) were positively correlated with survival and inversely with the GPS and stage. TG showed a direct correlation with stage only in patients with colon cancer. An inverse correlation between the levels of TC and the parameters of inflammation, in particular CRP ad IL-6, was observed. In the regression analysis IL-6 and CRP were predictors of TC and HDL, respectively. Albumin, a well known parameter of nutritional status, showed a direct correlation with HDL cholesterol levels, as in the general population. Conclusion Our results confirm the pathogenic role of chronic inflammation in inducing changes of lipid metabolism that characterize cancer patients. Lipid profile at diagnosis was correlated with prognostic factors such as stage of disease, GPS and survival. Disclosure All authors have declared no conflicts of interest.

Background and aims To test the safety and efficacy of a two-drug combination (including nutraceuticals, i.e. antioxidants) with carnitine + celecoxib for the treatment of cancer-related anorexia/cachexia syndrome (CACS) in the clinical practice. Primary endpoints: safety, increase of lean body mass (LBM) and improvement of quality of life. Secondary endpoints: increase of physical performance (tested by grip strength and 6-min walk test, 6MWT) and decrease of inflammation (assessed by serum levels of IL-6 and Glasgow prognostic score, GPS). Patients and methods Outpatients with advanced cancer at different sites with CACS (i.e. loss of body weight >5% of the pre-illness or ideal weight in the last3 months) were eligible to receive: L-carnitine 4 g/day + Celecoxib 300 mg/day. All patients received as basic treatment polyphenols 300 mg/day, lipoic acid 300 mg/day, carbocysteine 2.7 g/day, Vitamin E, A, C, all orally. Treatment duration was4 months. Results From June 2011 to April 2012, 50 patients with advanced cancer (all stage IV) at different sites were enrolled: 40 completed the treatment and were evaluable (mean age 63.8 ± 9.6, range 32-81 years). Results showed a significant increase of LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) from baseline as well as physical performance assessed by 6MWT. Quality of life (assessed by EORTC-QLQ-C30 and EQ-5D) also improved significantly. ECOG PS and GPS decreased significantly. The treatment was safe, no grade 3–4 toxicities occurred and no patient had to discontinue the treatment due to severe adverse events. Conclusions The results of the present study confirm the efficacy and safety of the two-drug combination regimen previously shown in a randomized clinical trial (Madeddu et al, Clinical Nutrition 31:176-182, 2012). Therefore, this simple, feasible, effective, safe, with favorable cost-benefit profile, two-drug approach could be suggested in the clinical practice as a treatment for CACS. Disclosure All authors have declared no conflicts of interest.

e19634 Background: Cancer patients with cachexia symptoms often show a lipid profile disorder, consisting in severe hypertriglyceridemia due to increased circulating free fatty acids and variable total cholesterol levels, decreased activity of lipoprotein lipase and increased lipolysis, which is correlated with proinflammatory cytokines levels, particularly IL-6 and TNFα. Recent evidence further confirms impairment of adipose tissue metabolism in inflammatory condition like cancer cachexia. The aim of this study was to assess the effect of nutritional supplementation with Omega 3 fatty acids (EPA and DHA) in the form of Krill Oil, on main parameters of blood lipid profile and on IL-6 and TNFα blood levels. Methods: In 2011, 34 IV stage cachectic patients (M/F 20/14; age range 55-85 y) with cancer at different sites were enrolled. 21 healthy subjects were studied as controls. All patients had high blood tryglicerides, low total cholesterol levels , high levels of blood IL-6 and TNFα compared to controls. Patients received 3 capsules (3 g/day) of krill oil (Superba™ Krill Oil, Aker Biomarine, Norway), which is an oil extract from the crustacean krill (Euphausia Superba) which contains Omega-3 series unsaturated fatty acids in phospholipidic form, of which 98 % are EPA and DHA mainly in phospholipid form. Treatment duration was 2 months. Results: A significant reduction of tryglicerides blood levels (148.23 ± 88.06 vs 114 ± 55.8 mg/dl) and a significant improvement of HDL cholesterol (42.5 ± 15.6 vs 60.9 ± 12.3 mg/dl) and Total Cholesterol (135.6 ± 46.3 vs 159 ± 41.1 mg/dl) was observed after treatment. Cytokines Il-6 and TNFα blood levels did not change significantly after treatment Conclusions: Nutritional supplementation with krill oil showed a positive activity in the regulation of blood lipid profile, involving different metabolic and inflammatory pathways, probably mainly affecting hormone-sensitive lipase activity. Our data suggest that krill oil could be useful in multi-targeted combined pharmaco-nutritional approaches to treat cancer-cachexia. Additional phase III clinical studies are warranted.

e19733 Background: Cancer-related anorexia/cachexia syndrome (CACS) is a multifactorial syndrome characterized by loss of lean body mass (LBM), metabolic alterations, chronic inflammation and fatig...

In spite of high level of morphological, reproductive and ecological conservativism, skates (suborder Rajoidea) are a group of highly diverse cartilaginous fish, whose evolution and diversification started since Late Cretaceous likely driven by Gondwanaland breakup and continental plate migration. More than 200 nominal species are presently inventoried being distributed over all Oceans, latitudes and marine ecosystems. Since speciation has been tremendous in such ancient monophyletic group, we have reconstructed evolutionary patterns and processes in the biogeographically monophyletic Eastern Atlantic skate faunas at multiple taxonomic levels by analyzing population genetic structure, phylogeographical and phylogenetic relationships in key-role taxa and clades. Variation patterns of genomic, nuclear and mitochondrial loci in Raja species revealed that geographical subpopulation structuring and cryptic speciation strongly contributed to the evolution of taxa diversity during Pliocene-Pleistocene. Comparative analysis of mitochondrial phylogenies and zoogeography of species belonging to the genera Raja, Leucoraja, Rajella, Dipturus, Amblyraja and Rostroraja revealed that present fauna diversity evolved since Early Miocene. The allopatric speciation and accumulation of genome divergence over time seem to be the predominant processes in shaping species diversity in these clades. However, the occurrence of relatively recent sympatric sister species indicate that also the rapid onset of highly efficient reproductive barriers could be relevant for cladogenesis in such group. Conspecific subpopulations geographically structured, adjacent sibling species and allopatric divergent sister species appeared rather like evolutionary animation of such still intriguing fish clade.