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Purpose: Biomarkers that predict response to immune checkpoint inhibitors (ICI) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) are needed. This retrospective study assessed tumor mutational burden (TMB) and outcomes in the phase II HAWK and CONDOR and phase III EAGLE studies of durvalumab with or without tremelimumab in platinum-resistant R/M HNSCC. Patients and Methods: Tumor samples from HAWK/CONDOR (N = 153) and blood samples from EAGLE (N = 247) were analyzed for TMB. Associations with survival were evaluated for tissue TMB (tTMB) at cutoffs from 10 to 20 mutations/megabase (mut/Mb) and for blood plasma TMB (bTMB) at cutoffs from 8 to 24 mut/Mb. Results: In HAWK/CONDOR, overall survival (OS) with durvalumab with or without tremelimumab was longer for high versus low tTMB: statistically significant differences were observed with durvalumab plus tremelimumab at tTMB ≥ 10 mut/Mb [HR, 0.52 (95% confidence interval, CI, 0.28–0.98)] and tTMB ≥ 12 mut/Mb [HR, 0.46 (95% CI, 0.24–0.86)]. In EAGLE, a significant OS benefit versus chemotherapy was observed with durvalumab and durvalumab plus tremelimumab at bTMB≥16 mut/Mb [HR, 0.39 (95% CI, 0.20–0.76) and 0.38 (95% CI, 0.19–0.78), respectively] but not bTMB < 16 mut/Mb [HR, 0.92 (0.61–1.37) and 0.92 (95% CI, 0.62–1.36), respectively]. A significant progression-free survival benefit was also observed in the ICI arms versus chemotherapy at bTMB ≥ 16 mut/Mb. Conclusions: Findings support TMB as a biomarker for predicting survival in patients with platinum-resistant R/M HNSCC treated with ICIs. The analysis of EAGLE demonstrated that bTMB was predictive of survival with ICI treatment versus chemotherapy in a large, randomized controlled study population.

FIG S2. Kaplan-Meier plot of OS in the durvalumab monotherapy, durvalumab plus tremelimumab and SoC treatment arms in the NLR ≤ 7 subgroup (A) and NLR > 7 subgroup (B) in EAGLE.

Supplementary Data

Purpose:Biomarkers that predict response to immune checkpoint inhibitors (ICI) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) are needed. This retrospective study assessed tumor mutational burden (TMB) and outcomes in the phase II HAWK and CONDOR and phase III EAGLE studies of durvalumab with or without tremelimumab in platinum-resistant R/M HNSCC.Patients and Methods:Tumor samples from HAWK/CONDOR (N = 153) and blood samples from EAGLE (N = 247) were analyzed for TMB. Associations with survival were evaluated for tissue TMB (tTMB) at cutoffs from 10 to 20 mutations/megabase (mut/Mb) and for blood plasma TMB (bTMB) at cutoffs from 8 to 24 mut/Mb.Results:In HAWK/CONDOR, overall survival (OS) with durvalumab with or without tremelimumab was longer for high versus low tTMB: statistically significant differences were observed with durvalumab plus tremelimumab at tTMB ≥ 10 mut/Mb [HR, 0.52 (95% confidence interval, CI, 0.28–0.98)] and tTMB ≥ 12 mut/Mb [HR, 0.46 (95% CI, 0.24–0.86)]. In EAGLE, a significant OS benefit versus chemotherapy was observed with durvalumab and durvalumab plus tremelimumab at bTMB≥16 mut/Mb [HR, 0.39 (95% CI, 0.20–0.76) and 0.38 (95% CI, 0.19–0.78), respectively] but not bTMB < 16 mut/Mb [HR, 0.92 (0.61–1.37) and 0.92 (95% CI, 0.62–1.36), respectively]. A significant progression-free survival benefit was also observed in the ICI arms versus chemotherapy at bTMB ≥ 16 mut/Mb.Conclusions:Findings support TMB as a biomarker for predicting survival in patients with platinum-resistant R/M HNSCC treated with ICIs. The analysis of EAGLE demonstrated that bTMB was predictive of survival with ICI treatment versus chemotherapy in a large, randomized controlled study population.

A series of new polymeric materials consisting of polylactide (PLA), polyethylene glycol (PEG) and berberine chloride (B) was evaluated. PEG was incorporated into the polymer matrix with the aim of obtaining a plasticizing effect, while berberine was added in order to obtain antibacterial properties in formed packaging materials. Materials were formed using the solvent-casting procedure. Fourier transform infrared spectroscopy and scanning electron microscopy were used so as to establish the structural changes resulting from the introduction of berberine. Thermogravimetry and differential scanning calorimetry were applied to study the thermal properties. Further, mechanical properties and differences in colour and transparency between the control sample and films containing berberine were also studied. The recorded data indicates that berberine formed a network on the surface of the PLA-based materials. Introduction of an active compound significantly improved thermal stability and greatly affected the Young’s modulus values of the studied polymeric films. Moreover, it should be stressed that the addition of the studied active compound leads to an improvement of the antibacterial properties, resulting in a significant decrease in growth of E. coli and the S. aureus bacteria cultures.

Recycling of polymers is one of the alternatives to reduce the impact of polymers presence on the environmental. However, the contaminants, defined as non-intentionally added substances, present in recycled material may migrate into food and also change its molecular structure. This work addresses the extractability/migration of contaminants from polypropylene (PP) samples into food simulants and the influence of these contaminants on the molecular structure of recycled PP. For this PP was contaminated with several substances to simulate a “worst-case” scenario and, then it was submitted to a recycling process. Extractability tests were performed by solid-phase microextraction and gas chromatography coupled to mass spectroscopy both to evaluate the presence of contaminants in the PP samples and their ability to migrate in food simulants. Additionally, molecular changes of the PP samples were evaluated by oscillatory rheometry. After washing and extrusion of the PP samples the extractability results showed considerable reductions of migrations in the food simulants and indicated, in some cases, compliance with regulations for using recycled polymer in contact with food. The residual contaminants were present in the polymer, the high temperatures and shear rates play an important role in molecular changes. Finally, the results highlight the importance of the use of rheological measurements to detect the influence of contaminants in recycled materials. Their presence result in material with different molar mass, that may be applied in different market applications.

Although most new biomaterials for food industry applications are labelled ‘100% natural fabrication’ and ‘chemical-free’, certain compounds may migrate from those materials to the food, compromis- ing the organoleptic characteristics and safety of the product. In this work, the degree of compound migration from dishes made with four different biomaterials: bamboo, palm leaf, wood and wheat pulp was investigated. Migration tests were carried out using three food simulants, 10% ethanol (sim- ulant A), 3% acetic acid (simulant B), and 95% ethanol (simulant D2). Unequivocal identification of non-intentionally added substances (NIAS) is challenging even when using high-resolution mass spectrometry techniques however, a total of 25 different non-volatile compounds from the migration tests were identified and quantified using Ultra-high performance liquid chromatography coupled to ion mobility quadrupole time-of-flight mass spectrometry (UPLC-IMS-MS). In the bamboo samples three oligomers, cyclic diethylene glycol adipate, 3,6,9,16,19,22-hexaoxabicyclo[22.3.1]-octacosa-1(28),24,26- triene-2,10,15,23-tetrone and 1,4,7,14,17,20-hexaoxacyclohexacosane-8,13,21,26-tetrone exceeded the specified limits of migration.

Polymeric films based on polylactide (PLA) with the addition of poly(ethylene glycol) (PEG) and a chloroformic extract of propolis were obtained. In the case of the studied films, polylactide (PLA) played the role of polymeric matrix and poly(ethylene glycol) was used as a plasticizer, while the extract of propolis was incorporated as a compound that could significantly affect the properties of the obtained materials, especially the water vapour permeation rate and the stability of the food products. Moreover, changes in structure, morphology, mechanical and storage properties as well as differences in colour, thickness and transparency after introducing propolis into the PLA–PEG system were determined. Based on the obtained results, it was established that the addition of the chloroformic extract of propolis significantly influences the most important properties taken into account during food packaging. It was also noticed that films with incorporated propolis were characterised by a significant improvement in the water vapour barrier property. Moreover, the obtained results prove that packaging containing a chloroformic propolis extract allow for the maintenance of the quality of the fruit stored for an extended period of time. To summarise, the application of a chloroformic propolis extract enables the formation of packaging materials that extend the shelf life of stored food products.

Seeds are highly resilient to the external environment, which allows plants to persist in unpredictable and unfavorable conditions. Some plant species have adopted a bet-hedging strategy to germinate a variable fraction of seeds in any given condition, and this could be explained by population-based threshold models. Here, in the model plant Arabidopsis (Arabidopsis thaliana), we induced secondary dormancy (SD) to address the transcriptional heterogeneity among seeds that leads to binary germination/nongermination outcomes. We developed a single-seed RNA-seq strategy that allowed us to observe a reduction in seed transcriptional heterogeneity as seeds enter stress conditions, followed by an increase during recovery. We identified groups of genes whose expression showed a specific pattern through a time course and used these groups to position the individual seeds along the transcriptional gradient of germination competence. In agreement, transcriptomes of dormancy-deficient seeds (mutant of DELAY OF GERMINATION 1) showed a shift toward higher values of the germination competence index. Interestingly, a significant fraction of genes with variable expression encoded translation-related factors. In summary, interrogating hundreds of single-seed transcriptomes during SD-inducing treatment revealed variability among the transcriptomes that could result from the distribution of population-based sensitivity thresholds. Our results also showed that single-seed RNA-seq is the method of choice for analyzing seed bet-hedging-related phenomena.

49 different non-volatile compounds were determined in Spanish Arctostaphylos uva-ursi leaves using UPLC®-ESI-Q-TOF with MSE technology. Both positive and negative electrospray ionization were applied. MarkerLynx® was proposed as a powerful tool to distinguish samples from eight wild populations of Spain by determining their non-volatile markers. Development of HRMS methods let to analysis of metabolites in plants. Antioxidant and antimicrobial capacities of different extracts were evaluated. Plant extract with the strongest antioxidant and simultaneous good antimicrobial capacity (Lierta) was chosen and incorporated in a multilayer packaging. Then, antioxidant capacity of the new packaging was evaluated and the efficient free radical scavenging properties were demonstrated.

3025 Background: Trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate composed of a humanized anti-HER2 monoclonal antibody and a topoisomerase I inhibitor payload, is approved for pts with unresectable or metastatic HER2+ BC with ≥2 prior anti-HER2–based therapies. T-DXd showed improved progression-free survival vs trastuzumab emtansine (T-DM1) as an earlier-line treatment (tx) for pts with HER2+ metastatic BC in the phase 3 DESTINY-Breast03 trial (Cortes J, et al. Ann Oncol. 2021;32:S1283-S1346. Abstract LBA1). Preliminary antitumor activity of T-DXd was shown in heavily pretreated pts with HER2-low advanced/metastatic BC in the phase 1 DS8201-A-J101 trial (Modi S, et al. J Clin Oncol. 2020;38:1887-1896). We report preliminary results from the dose-finding phase of 2 trials investigating T-DXd combination tx in HER2+ or HER2-low metastatic BC. Methods: DB-07 (phase 1b/2; NCT04538742) and DB-08 (phase 1b; NCT04556773) are 2-part, modular, open-label, multicenter trials of T-DXd combined with other anticancer tx in pts with advanced/metastatic BC that is HER2+ (DB-07) or HER2 low (DB-08). Part 1 of each study is an ongoing dose-finding phase; pts must have ≥1 prior tx for metastatic BC. Part 2 of each study is a dose-expansion phase; pts must have no (DB-07) or ≤1 (DB-08) prior tx for metastatic BC. We report preliminary results from the T-DXd + pertuzumab module of DB-07 part 1 (data cutoff: Oct 15, 2021) and T-DXd + anastrozole and T-DXd + fulvestrant modules of DB-08 part 1 (data cutoff: Sep 27, 2021); pts in the DB-08 modules must be hormone receptor positive. The part 1 primary objective was to assess safety and tolerability and determine the recommended phase 2 dose (RP2D) according to the modified toxicity probability interval-2 algorithm. Pts were followed up beyond the 21-day dose-limiting toxicity (DLT) period (28 days for T-DXd + fulvestrant) for safety events. Results: In DB-07, 7 pts were enrolled and received T-DXd 5.4 mg/kg + pertuzumab 420 mg (loading dose: 840 mg) every 3 wk (q3w; not evaluable for DLTs, n = 1). In DB-08, 6 pts were enrolled and received T-DXd 5.4 mg/kg q3w + anastrozole 1 mg daily (not evaluable for DLTs, n = 1); another 6 pts were enrolled and received T-DXd 5.4 mg/kg q3w + fulvestrant 500 mg every 4 wk (loading dose: 500 mg cycle 1 days 1 and 15). For all 3 modules, no DLTs were reported in any DLT-evaluable pts; the dose levels used in part 1 were approved to be the RP2Ds for use in the dose-expansion part of each corresponding module. No deaths on study or cases of interstitial lung disease/pneumonitis were reported to date. Conclusions: The RP2Ds for the T-DXd combinations were the standard doses for BC of each individual drug. These studies are ongoing, with additional T-DXd combinations being evaluated and further follow-up underway. Clinical trial information: NCT04538742; NCT04556773.

Grapefruit (Citrus × paradisi, Algerian variety) essential oil obtained by hydro‐distillation was evaluated as a substitute for vitamin E for margarine. The obtained IC₅₀ values were: 39.92 ± 0.18, 15.09 ± 0.02, and 4.42 ± 0.03 mg/ml by the 2,2‐diphenyl‐1‐picrylhydrazyl method, the reducing power and the β‐carotene/linoleic acid tests, respectively. These results were higher compared to those of the synthetic antioxidants. Values for BHA in DPPH and β‐carotene/linoleic acid assays were 0.158 ± 0.003 and 0.032 ± 0.000 mg/ml, respectively. The result of ascorbic acid for reducing power was 0.053 ± 0.001 mg/ml. Analysis of composition showed 128 volatile compounds. The limonene was the major compound (67.22%) followed by trans‐citral (5.39%) and isoauraptene (2.85%). All samples were fortified with 12.5, 50 and 100 µg/g of essential oil. The Rancimat test demonstrated that the lowest concentration of essential oil gave the best resistance to oxidation (22.6 hr). NOVELTY IMPACT STATEMENT: Grapefruit essential oil was used as a substitute for vitamin E for margarine, and it gave better resistance to oxidation than control samples. The presented solution could be successfully applied on an industrial scale.

The electrospun nanosystems containing poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and 1 wt% Fe doped ZnO nanoparticles (NPs) (with the content of dopant in the range of 0–1 wt% Fe) deposited onto polylactic acid (PLA) film were prepared for food packaging application. They were investigated by scanning electron microscopy (SEM), energy dispersive X-ray (EDX), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), antimicrobial analysis, and X-ray photoelectron spectrometry (XPS) techniques. Migration studies conducted in acetic acid 3% (wt/wt) and ethanol 10% (v/v) food simulants as well as by the use of treated ashes with 3% HNO3 solution reveal that the migration of Zn and Fe falls into the specific limits imposed by the legislation in force. Results indicated that the PLA/PHBV/ZnO:Fex electrospun nanosystems exhibit excellent antibacterial activity against the Pseudomonas aeruginosa (ATCC-27853) due to the generation of a larger amount of perhydroxyl (¿OOH) radicals as assessed using electron para-magnetic resonance (EPR) spectroscopy coupled with a spin trapping method. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Ante el actual consumo excesivo de plásticos y en especial, los destinados a un solo uso, la sociedad y las entidades gubernamentales han comenzado a tomar medidas para frenar la problemática medioambiental que generan. La búsqueda de alternativas ha promovido el desarrollo de menaje a partir de los denominados materiales naturales (biomateriales), sustancias biodegradables elaboradas a partir de materia vegetal como el bambú, la hoja de palma, la madera, la pulpa de trigo, etc. Aunque la mayoría de estos nuevos biomateriales se comercializan bajo una manufactura 100% “natural” y “libre de químicos”, es posible que ciertas sustancias migren desde el material al alimento que contienen, comprometiendo tanto las características organolépticas del producto como su seguridad. En este Trabajo de Fin de Grado se han identificado y cuantificado compuestos no volátiles procedentes de ensayos de migración con cuatro tipos de platos: bambú, hoja de palma, madera y pulpa de trigo. Los ensayos se han llevado a cabo empleando tres tipos de simulantes alimentarios (A, B y D2) siguiendo las condiciones establecidas en el Reglamento (UE)10/2011. Se han empleado dos técnicas de cromatografía líquida de alto rendimiento: UPLCQTOF-MSE y UPLC-IMS-QTOF/VION®. Posteriormente, se ha procedido a la cuantificación de los compuestos no volátiles identificados mediante UPLC-IMS-QTOF/VION® con el fin de evaluar si superan los límites de migración establecidos para alguno de ellos.Los resultados obtenidos muestran en primer lugar, diferencias en el número y cantidad de compuestos no volátiles migrantes según el tipo de plato estudiado. La mayor migración es la proveniente de platos de bambú y hoja de palma y la menor migración se encuentra en los platos de madera y pulpa de trigo. Respecto al origen de los compuestos no volátiles identificados algunos tienen un origen vegetal, provenientes de la propia materia prima (bambú, hoja de palma, madera o pulpa de trigo), aunque también se han identificado compuestos no volátiles procedentes de la manufactura del menaje y elaboración de plásticos, como aditivos, adhesivos, emolientes, etc.; y que pueden estar presentes en los platos por contaminación cruzada en su fabricación o bien haber sido añadidos para facilitar su manufactura. Respecto a la cuantificación de dichos compuestos, en general, se encuentran en concentraciones muy bajas, que no suponen un riesgo para la salud. Si bien, existen dos compuestos (el ácido 1,4-ciclohexanodicarboxílico en platos de bambú y el acetaminofeno en platos de hoja de palma) que superaron las restricciones legales establecidas, por lo que sería preciso continuar con los estudios de migración de este tipo de platos fabricados por este y otros proveedores, con objeto de asegurar que no se compromete la seguridad del consumidor empleando estos nuevos materiales en contacto con alimentos.

Nowadays, polypropylene is one of the most common polymers used in the food packaging industry due to its good functionality and relatively low cost. Nevertheless, usage of plastic disposable packaging can be a generator of plastic pollution having negative environmental effects. A feasible solution for this issue would be to recycle. The polypropylene samples were submitted to two processes, forced contamination, and recycling, and they were analyzed by solid-phase microextraction gas chromatograph-olfactometry-mass spectrometry. 45 different volatile compounds were identified and 9 of them presented distinct odoriferous activities. Among them, two important markers were detected: diethyl phthalate (probably coming from the catalyst of PP polymerization, intentionally added substance (IAS)), and glycerine (a marker of non-intentionally added substances (NIAS)).

The stability, surface micromorphology, and volatile organic compounds (VOCs) of silicone rubber baking molds (SRBMs) were tested while using the molds under severe conditions: baking at 175 °C, microwaving at 800 W, and freezing at −18 °C. Moreover, migration tests of SRBMs to food simulants (isooctane, 95% ethanol, and Tenax®) at 70 °C for 2 h (accelerated conditions) were performed. The initial total VOCs concentration was 2.53% higher than that recommended by BfR Recommendations on Food Contact Materials. Therefore, the SRBM samples were considered as badly tempered materials, and 18 different types of silicone oligomers were identified during the migration tests. The following percentage of silicone oligomers with a molecular weight lower than 1000 Da in isooctane, 95% ethanol, and Tenax® were detected: 70.7%, 91.8%, and 97.2%, respectively. It has been proven that previous baking treatments effectively reduced the content of silicone oligomers migrating from SRBMs.

Migration of N,N-Bis(2-hydroxyethyl) alkyl(C8–C18)amines from five different polypropylene capsules to Tenax® and coffee powder have been studied. A single step extraction-cleanup procedure using salting out liquid–liquid extraction (SALLE) method followed by ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) was applied. The critical parameters on the SALLE procedure such as extracting solvent, extracting volume, sample pH, salt and its concentration were optimized. The recovery values were in the range of 87.5%–106.5%. The %RSD were lower than 3.7%. The limit of detection was improved from 2.3 ng/g in Tenax® to 0.8 ng/g in coffee. The results indicated that the analyzed compounds have the potential to migrate from the polypropylene capsule containers to the coffee. In most of the cases, the migrated values were higher in Tenax® than in coffee in a range between 1.8 and 61%. One sample did not comply with the specific migration limit established by the European Commission.

The present work reports an experimental study on the optimization of phenolic compounds extraction from Citrus ✕ paradisi peels and the development of active packaging. Response surface methodology (RSM) was applied to investigate the effect of microwave-assisted extraction (MAE) for the recovery of total phenolic compounds (TPC). The TPC in the optimized extract were 31.10 mg gallic acid equivalent/100 g of dry weight (mg GAE/100 g dw) with strong antioxidant capacity. The bioactive compounds in the optimized extract were determined by ultrahigh performance liquid chromatography coupled to quadrupole time-of-flight with high energy mass spectrometry (UPLC-QTOF-MSE). Forty-five compounds were detected and qualified. The optimized extract obtained by MAE was used as an active antioxidant in multilayer food packaging films. The multilayer low-density polyethylene (LDPE)/polyethylene terephthalate (PET) containing 10% of MAE optimized extract provided the most antioxidant power acting as a free radical scavenger.

Recently oxobiodegradable polyethylene gained popularity as food packaging material due to its potential to reduce polymer waste. However, this type of material can release after its oxidation off-odour compounds that affect the organoleptic properties of packaged food. Odour compounds released from both polyethylene and oxobiodegradable polyethylene before and after oxidation under a free radicals flow were investigated after 1 day, 2 days and 3 days of oxidation. The samples were analysed using headspace solid phase microextraction followed by gas chromatography-mass spectrometry and headspace solid phase microextraction coupled to gas chromatography-olfactometry-mass spectrometry. Sixty-two different odorous compounds were identified. 4-methylthio-2-butanone (fruit), nonanal (fat) and 3,6-nonadienal (fat) were present in different materials before oxidation. Multiple headspace-solid phase microextraction has been used to quantify all analytes. The most abundant compound was (Z)-3-hexenyl hexanoate with a concentration range between 1.5791±0.1387 µg/g and 4.8181±0.3123 µg/g. Compounds such as 2-dodecenal, 2-octenal, 2-pentanol, 3-nonenal, 3,6-nonadienal, ethyl 3-methylbutanoate, ethyl octenoate, hexanone, isopropyl hexanoate, octanal were below their LOD evaluated using MS detector; however, they were detected by gas chromatography-olfactometry. The minimum LOD and LOQ were 0.011 µg/g and 0.036 µg/g, respectively.

For the first time, a silver nanoparticle substrate has been generated in situ through a cheap chemical reaction directly on a flexible polyethylene surface. Then, fast assessment of oxidation of an oxo-biodegradable polyethylene film has been carried out by means of surface-enhanced Raman scattering (SERS), achieving enhancement factors up to 3.2 × 105. Prior to the silver layer deposition, polymeric samples were exposed to different oxidation agents: ultraviolet light, heat, chemical oxidants and OH˙ radicals. The influence of oxidation treatment on the size and shape of silver nanoparticles was studied by scanning electron microscopy. Principal component analysis was performed and 85.4% of the accumulated variance was explained with three components, showing clear discrimination among oxidized samples after only 48 hours. However, conventional Raman spectroscopy was unable to find any difference. The proposed SERS method is able to detect significant oxidative changes in the polymer from 3 to 10 hours, considerably shorter than other techniques, such as FTIR, that require at least 10 days, and can be used for screening purposes or as an excellent complement to other analytical techniques.

New antioxidant polyamide was prepared by total immersion in active extract for 48 h. Its antioxidant performance was tested using DPPH (IC50 = 270 ± 21 μg/g) and ORAC (1.52 µmol Trolox/g). In vivo study was done using fresh minced meat stored at 4 °C and analysed after 0, 6, 13, 19, 23 days. After 23 days metmyoglobin (MetMbBK = 31.3 ± 2.9% and MetMbAOX = 25.9 ± 0.8%), CIE L*a*b* (a*BK = 15.0 ± 0.4 and a*AOX = 16.6 ± 0.3) and TBARS (MDABK = 0.0060 ± 0.0003 µg/g and MDAAOX = 0.0044 ± 0.0002 µg/g) showed an improvement of meat shelf life. The results showed that this active film protected meat during 23 days. Migration study to food simulants was done by UPLC®-QqQ-MS and UPLC®-ESI-Q-TOF-MSE. A decrease of oligomers migration (for caprolactam n = 3: BK = 0.050 ± 0.004 mg/Kg; AOX = 0.019 ± 0.001 mg/Kg) was found. Industrial relevance Nowadays, food industry is focused on improving shelf life of products by controlling its lipid oxidation using natural antioxidants. The obtained results let us design a new active packaging based on natural antioxidants for extending the shelf life of fresh minced meat at industrial scale.

A new biodegradable antioxidant active packaging for food applications based on antioxidants from medicinal and aromatic plants incorporated into a polylactic acid matrix was designed and developed. Melt blending processing technique was applied to prepare polylactic acid films loaded by sage and lemon balm leaves. Antioxidant properties of developed active films were investigated using the following methods: 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl and a home-made generator of hydroxyl radicals. In addition, reducing power and total phenolic content of polylactic acid films were checked. The results of antioxidant capacity showed that percentage of hydroxylation for active film with lemon balm and sage was 55.5% ± 0.1% and 67.4% ± 0.3%, respectively. The reducing power of active films increased 8 times in comparison to the blank samples. Moreover, extensive investigation of influence of sage and lemon balm leaves on material safety and type of migrants was performed using migration assays. The composition of both non-volatile and volatile compounds of different active packaging films was compared with neat polylactic acid film. Three different food simulants such as 95% (v/v) ethanol, 10% (v/v) ethanol and 3% (w/v) acetic acid were checked. It was shown that the addition of sage and lemon balm leaves into a polylactic acid structure decreased the migration of both linear and cyclic polylactic acid oligomers, currently not legislated by European Union. Besides, total absence or decrease of migration of volatile compounds were observed when using the active films. Both thermal and mechanical properties of films were also evaluated.

Food safety related to packaging materials and especially to plastics is nowadays under close scrutiny. Most plastics are able to transfer substances to the packaged food and the evaluation of risk assessment is essential. This chapter describes the main aspects of this topic, with a focus on multilayer, oxo-biodegradable plastics, recycled polymers, printing inks, non-intentionally added substances (NIAS), oligomers, active packaging and nanomaterials. Risk assessment needs to be applied to all packaging materials, which requires the identification and quantification of each individual compound released from the packaging to the food or food simulants. The last section is dedicated to analytical procedures applied for this purpose, which are challenging in the study of NIAS and risk assessment. Several real examples are included in which mass spectrometry plays an essential role.

A novel approach to incorporate green tea extract into polyethylene by extrusion technology has been studied. Green tea entrapped by inorganic capsules was incorporated into melted material and extruded without compromising its quality. The shelf-life of fresh meat from two types of active packaging was significantly extended for 3 0.25 days compared to blank samples. Significant difference was observed after 9th day of study in case of results of CIE L*a*b*, MetMb and organoleptic assay. Migration study of antioxidants from the materials was also performed by UHPLC-MS/TQ using food simulants. Amount of migrated catechins was in the range between 6.3 0.25 ± 0.25 3.3 and 228.4 0.25 ± 0.25 15.2 0.25 µg/kg (ratio 6:1). Regression coefficients (R) between 0.9925 and 0.9989 were obtained. Minimum LOD (0.001 0.25 µg/g) and LOQ (0.004 0.25 µg/g) were obtained for epicatechin gallate and catechin gallate while maximum LOD (0.057 0.25 µg/g) and LOQ (0.191 0.25 µg/g) were obtained for catechin.

Background In patients (pts) with HER2+ (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+) metastatic breast cancer (mBC), HER2-targeted therapies have greatly improved survival. However, for pts with HER2-low mBC (IHC 1+ or IHC 2+/ISH−), there are no approved HER2-directed therapies. In pts with hormone receptor (HR)+, HER2-low mBC whose disease progresses on standard first-line treatment (endocrine therapy [ET] and CDK4/6 inhibitors), median progression-free survival (PFS) with continued ET alone is ≈ 2 months, and with mTOR or PI3K inhibitors (in PIK3CA-mutant tumors) in the second-line setting, PFS ranges from 3.5 to 7.3 months, respectively (André F, et al. ESMO 2018; Dhakal A, at al. ASCO 2018; Rugo R, et al. ASCO 2020). For ET-refractory pts, chemotherapy (CTX) is the standard of care and has a poor benefit-risk ratio. The treatment landscape for pts with HR−, HER2-low mBC is even more limited, consisting largely of CTX (with or without PD-1/PD-L1 inhibitors in the first-line setting). T-DXd is an antibody-drug conjugate composed of a humanized HER2 antibody attached to a membrane-permeable topoisomerase I inhibitor payload via a cleavable tetrapeptide-based linker at a drug to antibody ratio of ≈ 8. In a recent phase 1b study, pts with heavily pretreated (median, 7.5 prior therapies) HER2-low advanced or metastatic breast cancer treated with T-DXd 5.4 or 6.4 mg/kg had a confirmed objective response rate (ORR) of 37.0% (20/54) by independent central review and a median PFS of 11.1 months, and the safety profile was generally manageable (Modi S, et al. J Clin Oncol. 2020;38:1887-1896). Here, we describe a phase 1b trial evaluating the safety, tolerability, and pharmacokinetics (PK) of T-DXd in combination with other anticancer agents in pts with HER2-low, HR+ or HR− mBC. Study Description DESTINY-Breast08 is a multicenter, open-label, 2-part study evaluating T-DXd combinations in pts with HER2-low mBC. The 5 treatment modules comprise T-DXd in combination with (1) capecitabine, (2) durvalumab + paclitaxel, (3) capivasertib, (4) anastrozole, and (5) fulvestrant. Part 1 (dose finding): Each treatment module will enroll 3 to 12 pts per dose level to determine the recommended phase 2 dose (RP2D) in combination; modules 1 through 3 will enroll irrespective of HR status, whereas modules 4 and 5 will be restricted to only HR+ pts. HR+ pts should have received ≥ 1 prior line of ET and ≥ 1 prior line of CTX; HR− pts should have received ≥ 1 prior line of CTX. Part 2 (dose expansion): Modules 1, 4, and 5 will enroll 20 pts, and modules 2 and 3 will enroll 40 pts using the RP2D determined in part 1 of each module. Patient eligibility per module in part 2 is as follows: Module 1 (HR+ or HR−): HR−, only 1 prior line of CTX for mBC; HR+, only 1 prior line of ET but no prior CTX for mBCModule 2 (HR−): no prior CTX for mBCModule 3 (HR−): only 1 prior line of CTX for mBCModules 4 and 5 (HR+): only 1 prior line of ET but no prior CTX for mBC The primary endpoint in part 1 is safety and tolerability and determination of RP2Ds. In part 2, the primary endpoint is safety and tolerability, and secondary endpoints include ORR, duration of response, and PFS (all by investigator assessment according to RECIST 1.1) as well as overall survival, PK, and immunogenicity. Citation Format: Komal Jhaveri, Erika Hamilton, Sherene Loi, Peter Schmid, Annie Darilay, Chen Gao, Gargi Patel, Magdalena Wrona, Fabrice Andre. Trastuzumab deruxtecan (T-DXd; DS-8201) in combination with other anticancer agents in patients with HER2-low metastatic breast cancer: A phase 1b, open-label, multicenter, dose-finding and dose-expansion study (DESTINY-Breast08) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-03-05.

Two essential oils and seven vegetable oils were tested in an in situ generator of hydroxyl radicals for determining their antioxidant capacity. Then twenty-two different active LDPE films were prepared by incorporating both the essential oils and vegetable oils. The antioxidant capacity, heat-sealing properties and aroma of developed films were determined. The films with the best antioxidant properties, containing flaxseed oil, ginger essential oil, grape seed essential oil and rose oil, were selected and applied as active packaging for fresh meat and tested at industrial scale. The optimum packaging corresponded to 50 μm LDPE film with flaxseed oil which was able to extend by 22% the shelf-life of fresh meat. It was proven that the concentration of flaxseed oil was crucial for antioxidant capabilities of film. Finally, derivatisation was applied to evaluate stability of flaxseed oil packaging. Stability assays suggest that active films should be kept in closed aluminium bags to prevent flaxseed oil oxidation by air and light.

A big challenge for today&rsquo, s industry is antimicrobial preservation and the safety of food. An effective solution to this problem can be a modern invention such as antimicrobial packaging. In the presented research the antimicrobial activity of two new active films incorporating silver, as IONPURE IPL, and ethyl lauroyl arginate (LAE) were evaluated, by employing a low-density polyethylene (LDPE) matrix and a biofilm material, respectively. Additionally, LAE was also incorporated into polystyrene (PS) pads by two different methods: by spraying and by immersion of the PS pads into an aqueous LAE solution. LDPE films containing silver did not show any antimicrobial activity against Escherichia coli and Aspergillus flavus, whereas the biofilm containing LAE reduced the growth of Salmonella enterica but did not inhibit Aspergillus flavus. The active PS pads, both sprayed and immersed in LAE solution, also showed antimicrobial activity, causing a reduction of 99.99% of Pseudomonas putida growth. Thermal treatment at 180 &deg, C for 6 and 15 min did not modify the antimicrobial activity of LAE against Salmonella enterica. Moreover, inductively coupled plasma-mass spectrometry (ICP-MS) analysis was performed to check the migration of silver from developed material intended for food packaging applications into food simulant.

The influences of temperature, exposure time, different types of polypropylene (PP), (3-Aminopropyl) triethoxysilane (KH550) used as coupling agent, sterilizing conditions on copper migration from nano‑copper/PP composite films into food/ food simulants were explored. Results showed that copper migrated more easily from polypropylene (PPH) films with a maximum rate of 34.51%, compared to those from copolymer polypropylene (PPR) and block copolymer polypropylene (PPB) to 3% acetic acid (w/v). Gamma (γ) irradiation could significantly increase the copper migration (P Industrial relevance Although nanomaterials are potentially beneficial for food packaging, migration of nanoparticles to the packaged food can be harmful to the human body. Therefore, it is very important to determine the presence and characterize the morphology of nanoparticles in food. In this paper, we have developed a new and effective packaging material containing nanoparticles and have explored the migration form and morphology in food simulants. In conjunction with the results of current study, nano‑copper/PP packaging material can be suggested for maintaining the product quality and has commercial potential.

Two antioxidant active packaging systems containing rosemary oleoresin and green tea extract for meat preservation were compared. Minced pork was packaged in active films and its quality was evaluated by sensory analysis, color, thiobarbituric acid reactive substances (TBARS) and total volatile basic nitrogen content (TVB-N). The active films coated with green tea extract showed high antioxidant capacity. The TBARS value of meat packaged with films containing 6 % green tea at day 14 was 0.62 mg of malonaldehyde/kg of meat. This value was equal to day 0 value of TBARS and 37 % lower than the TBARS value of pork in blank group at day 14. The TVB-N values obtained for 6 % green tea and 8 % rosemary at day 14 were 40 and 39 mg N/100 g meat, approximately 25 % lower than the blank. These results indicate the potential application of active films with green tea extract in meat preservation.

61 different non-volatile compounds were determined in Agaricus Bisporus sliced mushrooms using UHPLC/Q-TOF with MS(E) technology. Both positive and negative electrospray ionization were applied. Chemical profile of three parts of mushroom was created: cap, gills and stipe. The analysed mushrooms were oxidized to identify the non-volatile markers in their parts. MarkerLynx(®) was proposed as a powerful tool to distinguish mushrooms purchased in different countries (Spain and Portugal) by determining their non-volatile markers. Some metabolites were identified. Surprisingly a mix of polyethylene glycols (PEGs) was detected in cap and gills of mushrooms. Whole mushrooms were considered as vegetable resistant to migration from packaging compounds. Additionally migration tests were performed to determine the source of migrating compounds.

6548 Background: Baseline tumor and germline biomarkers in R/M HNSCC were analyzed for predictive potential in pts benefitting from D or D+T. Methods: In HAWK (NCT02207530), 112 pts (PD-L1 tumor cells [TC]≥25%) received D (10 mg/kg Q2W for ≤12 m); in CONDOR (NCT02319044), 67 pts (PD-L1 TC < 25%) received D (10 mg/kg Q2W for ≤12 m), 133 pts received D+T (D 20 mg/kg Q4W, T 1 mg/kg Q4W for ≤12 m), and 67 pts received T (10 mg/kg Q4W [7 doses] then Q12W [2 doses] for ≤12 m) VENTANA PD-L1 (SP263) Assay determined PD-L1 status. Paired FFPE archival tumor and PBMC samples (as germline control) in the HAWK and CONDOR trials were evaluated by whole exome sequencing (WES). Tumor mutation burden (TMB) was number of somatic mutations/megabase. HLA class I types were obtained via WES of PBMCs (CONDOR only). HPV and neutrophil-to-lymphocyte ratio (NLR) were tested locally in CONDOR. Wilcoxon, log-rank tests, and COX-PH models were used. Pooled D & D+T data were analyzed unless noted. Results: 153 pts had paired evaluable FFPE tumor and PBMC samples (HAWK, n = 48; CONDOR, n = 105). TMB distributions were similar between studies ( P= 0.43). TMB correlated with smoking ( P= 0.02) but not HPV ( P= 0.24), NLR ( P= 0.66), or PD-L1 status ( P= 0.43). Overall, high TMB (≥upper tertile) trended with longer OS vs low TMB in all evaluable pts (N = 153; 9.0 vs 5.6 m; HR = 0.70; 95% CI = 0.48-1.01); P= 0.06). In HAWK, there was no association of TMB with OS. In CONDOR, pts (D and D+T arms) with high TMB vs low had significantly longer OS (N = 76; 16.3 vs 5.3 m; HR = 0.53; 95% CI = 0.31-0.92). TMB and OS association was further assessed by increasing TMB cutoffs. Improved HRs trended with higher cutoffs; cutoffs ≥upper quartile significantly linked to OS.TMB was not associated with PFS or ORR. Pts with low PD-L1 and low TMB had worse OS compared to pts with high PD-L1 or high TMB. Pts with high NLR (≥median) and low TMB had significantly worse OS than pts with low NLR and high TMB (HR = 2.63, P< 0.001). Analysis of germline HLA alleles revealed significantly poorer survival for carriers of the HLA-B*15:01 allele (9.4%) (HLA-B variant status did not affect TMB and OS association in CONDOR). Germline HLA heterozygosity did not impact OS. Pts with mutations in ATM (5%), a DNA damage repair gene, also trended with prolonged OS. Conclusions: TMB is a possible predictive biomarker of IO HNSCC therapy. Combined analysis of NLR and TMB may provide additional PD-L1 data in assessing pts most likely to have long-term benefit. Clinical trial information: NCT002207530, NCT02319044 .

49 different non-volatile compounds were determined in Spanish Arctostaphylos uva-ursi leaves using UPLC

Active packaging plays a promising approach to extend the shelf-life of packed fresh mushrooms without compromising the fresh status. Four different active agents were incorporated into the packaging material to extend the shelf-life of packed mushrooms: sodium metabisulphite combined with citric acid; green tea extract; cinnamon essential oil and purple carrot extract. The sulphur dioxide-based packaging maintained the mushrooms white and appealing to consumers for a longer time than conventional packaging. The release of sulphur dioxide was carefully adjusted to avoid undesirable yellowing while keeping the whitening effect. Sulphur dioxide was determined in the mushrooms after the storage period, being the resulting concentration below the current limit of 10 μg/g. Green tea extract at high concentration maintained white colour of mushrooms longer than blank samples. Cinnamon essential oil and purple carrot extracts did not show enough antioxidant properties to inhibit the spoilage of mushrooms and/or extending their shelf-life.

Recycled materials such as expanded polystyrene (EPS) are increasing in the food market and some hazardous chemicals may exist in recycled PS resins. Therefore, a method of solid-phase microextraction and gas chromatography coupled to mass spectrometry followed by chemometric tools applied to the data obtained allowed the identification of markers for virgin and recycled EPS. The multivariate statistical analysis was developed to characterize the profile of volatile organic compounds (VOCs) in virgin and recycled EPS containers, and identify the potential VOCs markers responsible for EPS containers discrimination. A total of 99 compounds were identified in virgin and recycled EPS containers. Among these, 17 compounds contributing the most to the discrimination, were selected based on their variables importance in the projection (VIP) values, including o-xylene, acetophenone, ethylbenzene, α-ethylstyrene, 2-phenylpropenal, propylbenzene, 2-phenyl-1-propene, undecanal, benzoic acid ethyl ester, 2-ethyl-1-hexanol, decanal, benzylcarboxaldehyde, isopropylbenzene, 2,4-diphenyl-1-butene, dodecanal, benzaldehyde and nonanal. To evaluate the health risk of EPS containers, migration tests from EPS containers into two food simulants (10% ethanol, 3% acetic acid) were conducted. It should be highlighted that high amount of styrene was detected. Nevertheless, analysed materials accomplish with current EU Regulation No.10/2011. The proposed method finds the differentiation markers and provides a reliable tool to discriminate virgin and recycled EPS containers, which could be an additional tool for quality control of EPS containers.