Ferréol Salomon
email: ferreol.salomon@live-cnrs.unistra.fr

Cécile Vittori

Brice Noirot
email: brice.noirot@gmail.com

Elisa Pleuger
email: elisa.pleuger@ulg.ac.be

Carlo Rosa
email: carlorosa62@gmail.com

Ilaria Mazzini
email: ilaria.mazzini@igag.cnr.it

Pierre Carbonel
email: carbonel@free.fr

Hatem Djerbi
email: hatem.djerbi@eveha.fr

Piero Bellotti
email: piero.bellotti@gmail.com

Jean-Philippe Goiran
email: jean-philippe.goiran@mom.fr

Reconstruction of the Tiber Deltaic stratigraphic successions near Ostia using the PADM chart and tracking of the bedload-derived facies (Rome, Italy)

Keywords: chronostratigraphy, palaeoenvironments, PADM chart, Tiber delta. Highlights

Reconstruction of coastal transgression and progradation at the transition between the inner and outer delta plain near the archaeological site of Ostia;

• High sedimentation rates and deepening facies coeval to sea level jumps from the 9-8 k cal.

BP;

• Strong progradational phases are recorded around 4 k cal. BP, and from 2.8 to 2.6 k cal. BP;

• Identification of the Tiber River influence below and near the area of the archaeological site of Ostia: 4.2 to 4 k, 2.9 to 2.5 k, 2.5 to 1.7 k cal. BP;

• Synthesis of chronostratigraphic data and delineation of the envelope of the fluvial lateral mobility of the Tiber River since 6 k cal. BP (channel belt);

• PADM chart demonstrates great efficiency in interpreting stratigraphic successions in a river delta, in identifying evidence of coastline-trajectories and should help in constraining decompaction methods for deltaic sequences.

INTRODUCTION

Geomorphologically, river deltas are composed of a subaerial plain and a subaqueous part separated by the sea level or base level [START_REF] Wright | Variation in morphology of the river deltas as function of ocean wave and river discharge regimes[END_REF][START_REF] Wright | Sediment transport and deposition at river mouths: a synthesis[END_REF][START_REF] Wright | River Deltas[END_REF][START_REF] Coleman | Deltas: processes of deposition & models for exploration[END_REF][START_REF] Stanley | Worldwide Initiation of Holocene Marine Deltas by Deceleration of Sea-Level Rise[END_REF][START_REF] Hori | An early Holocene sea-level jump and delta initiation[END_REF][START_REF] Anthony | Human influence and the changing geomorphology of Mediterranean deltas and coasts over the last 6000 years: From progradation to destruction phase?[END_REF]. The existence of deltas depends primarily on the sediment load transported by the rivers to the sea and on the coastal and marine conditions. River channels are essential to route sediment to the coastlines and contribute to shape the deltas. In parallel, the sedimentary architecture of river deltas is mainly controlled by the base level that changes over time. It is a key factor that affects the characteristics and the location of fluvial, coastal, and marine facies. The reconstruction of the formation of river deltas during the Holocene depends on an integrated approach, taking into account a large range of data such as sediment facies, facies distribution, unconformities, relative sea level change, and accommodation space. In this regard, methods, notions, concepts, and visualisation tools developed in sequence stratigraphy are essential [START_REF] Posamentier | An overview of sequence-stratigraphic concepts: uses and abuses. Sequence stratigraphy and facies associations[END_REF][START_REF] Catuneanu | Principles of sequence stratigraphy[END_REF][START_REF] Catuneanu | Towards the standardization of sequence stratigraphy[END_REF][START_REF] Embry | Sequence stratigraphy as a "concrete" stratigraphic discipline[END_REF]. The time-stratigraphic context is also crucial to interpret sediment deposits in sequence stratigraphy. We suggest testing the Palaeoenvironmental-Age Depth Model (PADM chart) to visualise and interpret links between sedimentary facies, the relative sea level change rate, and the sedimentation rate (Salomon et al., 2016a). It corresponds to a classic age-depth model, but instead attempts to integrate a wide range of relevant data to interpret deltaic sediment deposits by using concepts developed in sequence stratigraphy.

In this study, we not only consider coastal and marine sediments and their relation to the Holocene base level, but also consider river deposits even though they follow different trends. It is very easy to spot the current channels, but multiple channels have existed throughout the Holocene that are less easy to identify. The palaeogeographical reconstruction of river mobility in deltas through the Holocene is a challenge. During the Early Holocene transgressive phase, the identification of river mouth palaeochannels is based on sedimentary cores. Their locations are mostly because of chance or a large chronostratigraphic database with many cores, palaeoenvironmental analyses and dates. In this case, palaeogeographical reconstruction of the Holocene transgression of the river mouth area of the Rhine is remarkable [START_REF] Hijma | Holocene transgression of the Rhine river mouth area, The Netherlands/Southern North Sea: palaeogeography and sequence stratigraphy[END_REF].

The locations of the deltaic river courses or the river mouths are easier for younger stages of delta formation: when base level rise stalls, a high stand is established and the delta system becomes progradational. The progradational phase started around 6500 cal. BP in the Mediterranean area because of sea level rising more slowly (Nile delta: Stanley andWarne, 1993, 1994;Po delta: Amorosi et al., 2017;[START_REF] Stefani | The interplay of eustasy, climate and human activity in the late Quaternary depositional evolution and sedimentary architecture of the Po Delta system[END_REF]; Rhone delta: [START_REF] Vella | Relative sea-level rise and neotectonic events during the last 6500 yr on the southern eastern Rhône delta, France[END_REF][START_REF] Vella | Evolution of the Rhône delta plain in the Holocene[END_REF] Ebro delta: [START_REF] Sornoza | Architectural stacking patterns of the Ebro delta controlled by Holocene high-frequency eustatic fluctuations, delta-lobe switching and subsidence processes[END_REF][START_REF] Cearreta | Holocene palaeoenvironmental evolution of the Ebro Delta (Western Mediterranean Sea): Evidence for an early construction based on the benthic foraminiferal record[END_REF]. From these youngest millennia, some morphological changes are noticeable on the ground surface. Palaeochannels, beach ridges, and palaeolagoons can be traceable through aerial photography, satellite imagery, old maps, or LiDAR data. Palaeochannels can be characterised by their morphologies (levees, ridges and swales, cut-off channels) or their location is inferred when they cut pre-existing beach ridges [START_REF] Pranzini | Airborne LiDAR survey applied to the analysis of the historical evolution of the Arno River delta (Italy)[END_REF][START_REF] Ullmann | Preliminary results on the paleo-landscape of Tell Basta /Bubastis (eastern Nile delta): An integrated approach combining GIS-Based spatial analysis, geophysical and archaeological investigations[END_REF][START_REF] Gebremichael | Assessing land deformation and sea encroachment in the Nile Delta: A radar interferometric and inundation modeling approach[END_REF]. Alternatively, palaeoriver mouths can be located using beach ridges in cuspidate deltas [START_REF] Stefani | The interplay of eustasy, climate and human activity in the late Quaternary depositional evolution and sedimentary architecture of the Po Delta system[END_REF][START_REF] Vella | Evolution of the Rhône delta plain in the Holocene[END_REF] or by producing submarine topographic/geophysical profiles of subaqueous lobe deltas [START_REF] Shaw | Airborne radar imaging of subaqueous channel evolution in Wax Lake Delta, Louisiana, USA[END_REF]. However, through time, floodplain deposits and coastal dynamics, respectively, contribute to cover and rework morphological evidence.

Typically, studies on coastal palaeodynamics are more numerous than studies on fluvial palaeodynamics of the adjacent delta plain inland. This can be attributed to a better record of coastal morphologies on aerial photography/satellite imagery (beach-ridges), and also because coastal dynamics are better expressed vertically in relation to the base level (RSL -Relative Sea Level).

Progradational beach ridges can extend widely along the coast and can be studied using perpendicular cross sections (dates of the progradational phases and identification of potential erosional or stability phases) [START_REF] Bicket | A multiscale geoarchaeological approach from the Laurentine shore (Castelporziano, Lazio, Italy)[END_REF] for the Tiber delta). The location of palaeochannels is more difficult to predict (especially when it involves avulsion processes), and river systems often rework older alluvial morphologies. In recent years, this discrepancy between coastal and fluvial studies tends to be filled by an increasing number of sedimentary drillings, as well as the development of LiDAR data. For example, the recurrent discussion about the identification of Nile River branches is currently reexamined by LiDAR data from TamDEM-X [START_REF] Gebremichael | Assessing land deformation and sea encroachment in the Nile Delta: A radar interferometric and inundation modeling approach[END_REF][START_REF] Ullmann | Preliminary results on the paleo-landscape of Tell Basta /Bubastis (eastern Nile delta): An integrated approach combining GIS-Based spatial analysis, geophysical and archaeological investigations[END_REF]. This paper focuses on cores drilled between 2011 and 2013 down to 25m in the area of the archaeological site of Ostia (Figs. 1 and2). The studied cross section includes the turning point between the last phase of the transgression and the early phases of the progradation (Figs. 2 and3).

Palaeoenvironmental Age-Depth Models (PADM charts) are made to clarify the interpretation of this coastal area and display the effect of river erosion on the sedimentary sequences.

GEOLOGICAL AND GEOMORPHOLOGICAL SETTINGS

The Tiber delta is located in the Tyrrhenian extensional continental margin. This configuration started during the Miocene and shaped the landscape with northwest/southeast normal faulting and northeast/southwest transverse systems in the lower Tiber [START_REF] Funiciello | La geologia di Roma. Il centro storico[END_REF].

The Tiber delta is developing near Upper-Middle Pleistocene volcanoes on the east of the Tyrrhenian Sea back arc basin (Karner et al., 2001b) and takes part of the Quaternary succession starting in the Late Pliocene near Rome [START_REF] Milli | Depositional setting and high-frequency sequence stratigraphy of the Middle-Upper Pleistocene to Holocene deposits of the Roman Basin[END_REF]Karner et al., 2001a). General uplift of the area is related to volcanic activity and isostasy [START_REF] De Rita | Geological-petrological evolution of the Ceriti Mountains area (Latium, central Italy)[END_REF][START_REF] Ferranti | Markers of the last interglacial sea-level high stand along the coast of Italy : Tectonic implications[END_REF][START_REF] Mantovani | A review on the driving mechanism of the Tyrrhenian-Apennines system: Implications for the present seismotectonic setting in the Central-Northern Apennines[END_REF].

Active faults in the Tiber delta during the Holocene are still discussed by different research teams [START_REF] Bigi | Mantle-derived CO2 migration along active faults within an extensional basin margin (Fiumicino, Rome, Italy)[END_REF][START_REF] Ciotoli | Tiber delta CO2-CH4 degassing: A possible hybrid, tectonically active Sediment-Hosted Geothermal System near Rome[END_REF][START_REF] Marra | Historical faulting as the possible cause of earthquake damages in the ancient Roman port city of Ostia[END_REF] (Fig. 1).

The Tiber delta is a wave dominated delta [START_REF] Bellotti | Sequence stratigraphy and depositional setting of the Tiber delta: integration of high-resolution seismics, well logs, and archeological data[END_REF]. The Tiber River is 405 km long with a spring at 524 m a.s.l. The watershed area is 17,375 km² (Autorità di Bacino del Fiume Tevere, 2006). Today, the regime of the Tiber River is pluvio-nival with maximum mean discharge in winter (February) and minimum mean discharge in summer (August). During the twentieth to twenty-first centuries the annual water discharge is 213 m 3 /s, with a minimum at 62 m 3 /s (August 1986) and a maximum at 2750 m 3 /s (December 1937) [START_REF] Bersani | Le Piene del Tevere a Roma dal V secolo a.C. all'anno[END_REF]. The first palaeogeographical reconstructions date to the 1950s and 1960s with the aerial-photo interpretation of J. Bradford (1957 -Fig. 23) and a geological map [START_REF] Dragone | Note illustrative del Foglio 149 Cerveteri della Carta Geologica d'Italia[END_REF]. In the context of the construction of the International Airport of Rome -Fiumicino, [START_REF] Segre | Considerazioni sul Tevere e sull'Aniene nel Quaternario[END_REF] hypothesized the presence of many palaeochannels in the Tiber delta. The first palaeogeographical reconstruction, based on sedimentary cores and radiocarbon dates, was proposed in the 1980s [START_REF] Belluomini | Evoluzione recente del delta del Tevere[END_REF]. Later, reconstructions based on an integrated approach of sedimentary cores, sedimentological analysis, palaeoenvironmental data, and sequential stratigraphy were coordinated by Bellotti [START_REF] Bellotti | Sequence stratigraphy and depositional setting of the Tiber delta: integration of high-resolution seismics, well logs, and archeological data[END_REF][START_REF] Bellotti | Physical stratigraphy and sedimentology of the Late Pleistocene-Holocene Tiber Delta depositional sequence[END_REF][START_REF] Bellotti | La piana deltizia del Fiume Tevere: analisi di facies ed ipotesi evolutiva dell'ultimo "low stand" glaciale all'attuale[END_REF][START_REF] Bellotti | Late Quaternary landscape evolution of the Tiber River delta plain (Central Italy): new evidence from pollen data, biostratigraphy and 14C dating[END_REF][START_REF] Bellotti | Landscape diachronic reconstruction in the Tiber demta during historical time: A holistic approach[END_REF], and more recently by Milli [START_REF] Amorosi | Late Quaternary depositional architecture of Po and Tevere river deltas (Italy) and worldwide comparison with coeval deltaic successions[END_REF][START_REF] Milli | The transition from wave-dominated estuary to wave-dominated delta: The Late Quaternary stratigraphic architecture of Tiber River deltaic succession (Italy)[END_REF][START_REF] Milli | From river to shelf, anatomy of a high-frequency depositional sequence: The Late Pleistocene to Holocene Tiber depositional sequence[END_REF]. These studies contributed in reconstructing the formation of the prodelta, the delta front, and the deltaic plain during the Holocene. Traditionally, the Tiber delta plain is divided into two main geomorphological units; the inner delta plain occupied by the palaeolagoon of Ostia and Maccarese, and the outer delta plain corresponding to the prograded deltaic plain.

Similar to other river deltas across the world, two periods characterise the evolution of the Tiber river mouth since the Last Glacial Maximum. Following the quick sea level rise starting around 16,500 cal. BP [START_REF] Lambeck | Sea level and global ice volumes from the Last Glacial Maximum to the Holocene[END_REF], transgression affected the Tiber River mouth and contributed to the formation of a specific sedimentary sequence: the Transgressive Systems Tract (TST).

Afterwards, since 7000-6000 cal. BP, sea level rise slowed down and the Tiber delta started to form a large prograded plain [START_REF] Bellotti | Late Quaternary landscape evolution of the Tiber River delta plain (Central Italy): new evidence from pollen data, biostratigraphy and 14C dating[END_REF]. During this second period, sedimentary deposits belong to the Highstand Systems Tract (HST). More detailed analysis of the phases of progradation and erosion are proposed by [START_REF] Giraudi | Evoluzione tardo-olocenica del delta del Tevere[END_REF] and [START_REF] Bicket | A multiscale geoarchaeological approach from the Laurentine shore (Castelporziano, Lazio, Italy)[END_REF]. For the last 2000 yr, archaeological and historical data can be used to reconstruct fluvial and coastal mobility (Le [START_REF] Gall | Le Tibre, fleuve de Rome dans l'antiquité[END_REF][START_REF] Bersani | Evoluzione storica della linea di costa in prossimità della foce del Tevere[END_REF] and can be combined with sedimentary cores, 14 C and OSL dates [START_REF] Salomon | Géoarchéologie du delta du Tibre : Evolution géomorphologique holocène et contraintes hydrosédimentaires dans le système Ostie -Portus[END_REF].

Many hypotheses exist for the location of the river channels or channel belts in the Tiber delta during the Holocene [START_REF] Dragone | Note illustrative del Foglio 149 Cerveteri della Carta Geologica d'Italia[END_REF][START_REF] Segre | Considerazioni sul Tevere e sull'Aniene nel Quaternario[END_REF][START_REF] Bellotti | Late Quaternary landscape evolution of the Tiber River delta plain (Central Italy): new evidence from pollen data, biostratigraphy and 14C dating[END_REF][START_REF] Giraudi | Late Holocene evolution of Tiber river delta and geoarchaeology of Claudius and Trajan Harbor, Rome[END_REF]. The topography of the unconformity at the base of the Tiber Depositional Sequence confines the lateral instability of the river channels in the centre of the Tiber delta during the early stages of the transgression (13,000 -9000 cal. BP - [START_REF] Bellotti | Late Quaternary landscape evolution of the Tiber River delta plain (Central Italy): new evidence from pollen data, biostratigraphy and 14C dating[END_REF][START_REF] Milli | The transition from wave-dominated estuary to wave-dominated delta: The Late Quaternary stratigraphic architecture of Tiber River deltaic succession (Italy)[END_REF]. Main phases of evolution suggest a channel belt of the Tiber in the central axis of the delta during the Early Holocene (> 9000 cal. BP - [START_REF] Bellotti | Late Quaternary landscape evolution of the Tiber River delta plain (Central Italy): new evidence from pollen data, biostratigraphy and 14C dating[END_REF][START_REF] Milli | The transition from wave-dominated estuary to wave-dominated delta: The Late Quaternary stratigraphic architecture of Tiber River deltaic succession (Italy)[END_REF][START_REF] Milli | From river to shelf, anatomy of a high-frequency depositional sequence: The Late Pleistocene to Holocene Tiber depositional sequence[END_REF], and a displacement of the channel belt towards the south until today (< 9000 cal. BP - [START_REF] Bellotti | Late Quaternary landscape evolution of the Tiber River delta plain (Central Italy): new evidence from pollen data, biostratigraphy and 14C dating[END_REF]. The identification of palaeochannels visible in aerial photography, satellite imagery, and old maps makes it possible to reconstruct the evolution of the lateral mobility of the Tiber during at least the last 2500 yr [START_REF] Arnoldus-Huyzendveld | Alcune considerazioni sullo sviluppo storico dell'ansa dell Tevere presso Ostia e sul porto-canale[END_REF][START_REF] Arnoldus-Huyzendveld | Traces of historical landscapes preserved in the coastal area of Rome[END_REF][START_REF] Salomon | Long-Term Interactions between the Roman City of Ostia and Its Paleomeander, Tiber Delta, Italy[END_REF]2018). The first detailed description of the bedload-derived facies for the Tiber delta is proposed for the bottom of the channels of the meander of Ostia dated between the end of the first millennium BCE and 1557 CE (bedload-derived deposits at the bottom of the point bar and at the bottom of the oxbow - [START_REF] Salomon | Long-Term Interactions between the Roman City of Ostia and Its Paleomeander, Tiber Delta, Italy[END_REF]. Studies based on cores drilled in the coastal area [START_REF] Goiran | Palaeoenvironmental reconstruction of the ancient harbors of Rome: Claudius and Trajan's marine harbors on the Tiber delta[END_REF][START_REF] Salomon | Géoarchéologie du delta du Tibre : Evolution géomorphologique holocène et contraintes hydrosédimentaires dans le système Ostie -Portus[END_REF][START_REF] Goiran | Geoarchaeology confirms location of the ancient harbour basin of Ostia (Italy)[END_REF], in the palaeolagoon of Ostia [START_REF] Bellotti | The Tiber river delta plain (central Italy): Coastal evolution and implications for the ancient Ostia Roman settlement[END_REF][START_REF] Vittori | Palaeoenvironmental evolution of the ancient lagoon of Ostia Antica (Tiber delta, Italy)[END_REF] and in palaeochannels of the Tiber River of Ostia [START_REF] Salomon | Long-Term Interactions between the Roman City of Ostia and Its Paleomeander, Tiber Delta, Italy[END_REF][START_REF] Salomon | Geoarchaeology of the Roman port-city of Ostia: Fluvio-coastal mobility, urban development and resilience[END_REF], suggest a migration of the last section of the course of the Tiber in its delta towards the south between 2800 cal. BP and 2300-1700 cal. BP. Most of the evidence is from indirect fluvial influence suggested by bioindicators [START_REF] Bellotti | The Tiber river delta plain (central Italy): Coastal evolution and implications for the ancient Ostia Roman settlement[END_REF][START_REF] Goiran | Geoarchaeology confirms location of the ancient harbour basin of Ostia (Italy)[END_REF]. Recently, coarse bedload- derived facies from this period have been dated just north of Ostia (Hadler et al., in press, Core TEV2A/TEV DP8), and could be product of the initial phase of formation of the palaeomeander of Ostia [START_REF] Salomon | Long-Term Interactions between the Roman City of Ostia and Its Paleomeander, Tiber Delta, Italy[END_REF][START_REF] Salomon | Geoarchaeology of the Roman port-city of Ostia: Fluvio-coastal mobility, urban development and resilience[END_REF]. Earlier phases of the fluvial evolution are still to be tracked and dated with precision.

METHODS

This paper includes new chrono-stratigraphical and palaeoenvironmental data from Cores PO-1 and 2, CAT-3 and MO-2. The upper parts of these cores were previously published and studied with a geoarchaeological perspective. These upper stratigraphic sequences were interpreted in regards to the evolution of the Roman city of Ostia (Core MO-2 in [START_REF] Salomon | Long-Term Interactions between the Roman City of Ostia and Its Paleomeander, Tiber Delta, Italy[END_REF]Cores CAT-2 and CAT-3 in Salomon et al., 2018) and its harbours (PO-1 and 2 in [START_REF] Goiran | Geoarchaeology confirms location of the ancient harbour basin of Ostia (Italy)[END_REF]. Core LOA-1 [START_REF] Vittori | Palaeoenvironmental evolution of the ancient lagoon of Ostia Antica (Tiber delta, Italy)[END_REF], Core CAT-2 [START_REF] Salomon | Geoarchaeology of the Roman port-city of Ostia: Fluvio-coastal mobility, urban development and resilience[END_REF] and Core OST-4 [START_REF] Hadler | Temple-complex postdates tsunami deposits found in the ancient harbour basin of Ostia (Rome, Italy)[END_REF] complement the cross section.

Cores PO-1 / PO-2, CAT-2 / CAT-3, and MO-2 were drilled between 2010 and 2013.

Stratigraphies record a large range of sedimentary facies and were analysed using palaeoenvironmental indicators classically used in such context (Figs. 4,6,and 8). Before any destructive analysis, the magnetic susceptibility of the core sequences were measured in CGS using a Bartington MS2E1 [START_REF] Dearing | Environmental magnetic susceptibility[END_REF]. In the Tiber delta, the magnetic susceptibility records content of clinopyroxenes and magnetites coming from the volcanic areas of the watershed [START_REF] Belfiore | Il delta del Tevere: le facies sedimentarie della conoide sommersa. Un'analisi statistica dei caratteri tessiturali, microfaunistici e mineralogici[END_REF]. High magnetic susceptibility is primarily observed in the sand fraction of the fluvial bedloadderived facies or in coastal sandy placers formed along the coast. Magnetic susceptibility is mainly used here to support the delineation of stratigraphical units. Palaeohydrodynamic context is deducted from grain-size analyses. Wet sieving at 63µm and 2mm was systematically applied to the sediments sampled from the different units of the core stratigraphies. For selected samples distributed in all stratigraphical units, wet sieving was completed with detailed grain size analysis conducted on a laser particle analyzer from Malvern Panalytical. Common grain size indicators such as sorting and median were calculated [START_REF] Folk | Brazos River bar [Texas]; a study in the significance of grain size parameters[END_REF][START_REF] Cailleux | Initiation à l'étude des sables et des galets[END_REF]. Loss-on-Ignition measurements were also conducted on sediments heated at 550°C for four hours (for organic matter) and 950°C for two hours (for carbonates) following the method proposed by [START_REF] Heiri | Loss on ignition as a method for estimating organic and carbonate content in sediments: reproducibility and comparability of results[END_REF].

Palaeoecological context is based on the analysis of macrofauna and ostracods. Macrofauna was extracted from sieved samples >2 mm [START_REF] Perès | Nouveau manuel de bionomie benthique de la Mer Méditerranée[END_REF][START_REF] Bellan-Santini | Les biocénoses marines et littorales de Méditerranée, synthèse, menaces et perspectives[END_REF]. In the sieved sediments (63 µm < x < 1 mm), all ostracods (small bivalved crustaceans) were picked and normalised to 10 g of sediment weight [START_REF] Carbonel | Ostracods and the transition between fresh and saline waters[END_REF][START_REF] Frenzel | The use of ostracods from marginal marine, brackish waters as bioindicators of modern and Quaternary environmental change[END_REF][START_REF] Mazzini | Late Holocene palaeoenvironmental evolution of the Roman harbour of Portus, Italy[END_REF][START_REF] Ruiz | Marine and brackish-water ostracods as sentinels of anthropogenic impacts[END_REF][START_REF] Vittori | Palaeoenvironmental evolution of the ancient lagoon of Ostia Antica (Tiber delta, Italy)[END_REF]. Macrofauna and ostracods were identified in order to deduce, in particular, the freshwater and marine influences and the depositional context [START_REF] Goiran | Recherches géomorphologiques dans la région littorale d'Alexandrie en Egypte (PhD thesis in Physical Geography)[END_REF][START_REF] Marriner | Geoarchaeology of Sidon's ancient harbours, Phoenicia[END_REF][START_REF] Goiran | Géoarchéologie des ports de Claude et de Trajan, Portus, delta du Tibre[END_REF]. Ostracods from Core PO-2 presented here were also published in [START_REF] Sadori | Palynology and ostracodology at the Roman port of ancient Ostia (Rome, Italy)[END_REF].

Palaeoenvironmetal Age-Depth Models (PADM charts) are used to interpret chronometric and integrated stratigraphy data (Salomon et al., 2016a) (Figs. 5, 7 and 9). Developed to interpret ancient coastal harbours and to cross datasets of different types and disciplines, this PADM chart is related to geohistory diagrams, also called backstrip diagrams [START_REF] Van Hinte | Geohistory analysis-application of micropaleontology in exploration geology[END_REF][START_REF] Allen | Basin analysis: Principles and application to petroleum play assessment[END_REF]. The PADM chart is based on a classic age-depth model, with stratigraphical and palaeoenvironmental context recorded on the y-axis, and palaeogeographical and chronological information transferred to the x-axis. The standardised PADM chart integrates all relevant data to interpret the stratigraphical sequences. A quick glance at the charts offers an overview of the local modelled sea level curve, the different apparent sedimentation curves, the results of the palaeoenvironmental analyses and their interpretations. Most importantly, this chart simplifies the identification of sediments related to the Transgressive Systems Tract or the Highstand Systems Tract. Additionally, the systematic combination of the sea level curve with a sedimentation curve exposes clear correlations to their respective evolutions or the variability of the accommodation space through time.

The sedimentation curve is reconstructed with no vertical adjustments -i.e., without any decompaction, subsidence or uplift corrections. The calibration of radiocarbon ages has been performed using the curve proposed by [START_REF] Reimer | IntCal13 and Marine13 radiocarbon age calibration curves 0-50,000 years cal BP[END_REF] with the software OxCal [START_REF] Ramsey | Radiocarbon calibration and analysis of stratigraphy: the OxCal program[END_REF] Ramsey and Lee, 2013) (Table 1). No model was used to calibrate and narrow down age ranges (e.g., Bayesian model). Interpretative sedimentation curves are proposed based on radiocarbon dates.

Between dates the sedimentation curves can be adjusted depending on the processes hypothesised (e.g., sediment starvation, condensed section). Only the apparent sedimentation curve and the apparent accommodation space are reported here. Interpretations will be proposed consequently.

Many papers suggest decompaction methods taking into account the stratigraphy, porosity, grain size, organic matter content, deposition rate, and overload weight (water or sediment) [START_REF] Van Hinte | Geohistory analysis-application of micropaleontology in exploration geology[END_REF][START_REF] Van Asselen | Effects of peat compaction on delta evolution: A review on processes, responses, measuring and modeling[END_REF][START_REF] Kominz | Lithology Dependence of Porosity In Slope and Deep Marine Sediments[END_REF][START_REF] Allen | Basin analysis: Principles and application to petroleum play assessment[END_REF][START_REF] Johnson | The role of sediment compaction and groundwater withdrawal in local sea-level rise, Sandy Hook, New Jersey, USA[END_REF]. A decompaction method was also applied to the Tiber delta [START_REF] Marra | Chronostratigraphic and lithologic features of the Tiber River sediments (Rome, Italy): Implications on the post-glacial sea-level rise and Holocene climate[END_REF]. However, the unconformity at the base of the Tiber Depositional Sequence is not precisely known in the studied area (only estimations are proposed in Milli et al., 2013, between 30 and 40 m below Ostia) and stratigraphies of the Late Pleistocene / Early Holocene are not known for the cores presented here. If the interplay between sedimentation rate, compaction, and tectonics can be discussed, the main phases of the chronology proposed is not affected by this vertical instability. The sea level curve used in this paper is an eustatic curve with glacio-hydro-isostatic predictions proposed by [START_REF] Lambeck | Sea level change along the Italian coast during the Holocene and projections for the future[END_REF] for the Tiber delta. In Fig. 3, this local modelled curve is compared to the best estimate of the ice-volume equivalent global sea level function [START_REF] Lambeck | Sea level and global ice volumes from the Last Glacial Maximum to the Holocene[END_REF] and the modelled sea level curve for the Tiber delta area from [START_REF] Vacchi | Multiproxy assessment of Holocene relative sea-level changes in the western Mediterranean: Sea-level variability and improvements in the definition of the isostatic signal[END_REF] (ICE-5G VM2 Model). The age-depth models (apparent sedimentation rates) and the palaeoenvironments will be interpreted taking into account their relations to the local sea level curve prediction. The sedimentation curves proposed in this paper are not taking into account the elevation loss caused by sediment compaction [START_REF] Van Asselen | Effects of peat compaction on delta evolution: A review on processes, responses, measuring and modeling[END_REF][START_REF] Marra | Chronostratigraphic and lithologic features of the Tiber River sediments (Rome, Italy): Implications on the post-glacial sea-level rise and Holocene climate[END_REF]. Possible vertical changes (compaction, neotectonic) will be considered in regards to several parameters: it is suggested that the aspect of the apparent sedimentation curve is constrained by the palaeoenvironmental characteristics of the deposits (e.g., subaerial and subaqueous bioindicators, shallow or deep water sediment characteristics), the depositional processes involved, the geometry and the temporal development of the transgressive/progradational sequences ( [START_REF] Tamura | Temporal development of prograding beachshoreface deposits: the Holocene of Kujukuri coastal plain, eastern Japan[END_REF][START_REF] Tanabe | Holocene evolution of the Song Hong (Red River) delta system, northern Vietnam[END_REF][START_REF] Milli | From river to shelf, anatomy of a high-frequency depositional sequence: The Late Pleistocene to Holocene Tiber depositional sequence[END_REF], and to a certain extent by the modelled local sea level curve [START_REF] Lambeck | Sea level change along the Italian coast during the Holocene and projections for the future[END_REF] for the present paper). In Group 1, Core PO-2 will be completed by cores PO-1 (new data for the lower part of the sequence) and Core OST-4 [START_REF] Hadler | Temple-complex postdates tsunami deposits found in the ancient harbour basin of Ostia (Rome, Italy)[END_REF]. In Group 2, Core CAT-3 will be completed by Core CAT-2. Core MO-2 is the only one forming Group 3, and Core LOA-1 is the only one for Group 4.

ANALYSES

Core PO-2 is the deepest reaching core in the Ostia study area (25 m b.s.l.) and the sedimentation refers to a long period of time between 8000 and 2000 cal. BP (Figs. 4 and5). Four main units were observed below the Roman harbour of Ostia, Units A to D. Unit A is composed of bedded grey silty sand. Around 22 m b.s.l., few cm-layers are composed of silts or organic material.

Ostracods mainly reveal a coastal assemblage, mostly brackish lagoonal, but with a large amount of marine and phytal coastal species. No date is available for this unit. Silty sands are still deposited in Sub-unit B1 but interbedded with grey silty clay. In Sub-unit B2, the deposits are compact grey silty clay with no more sandy layers visible (96% of silt and clay). Ostracod assemblage is similar to Unit A.

Organic material was radiocarbon dated at 7677 to 7588 cal. BP (6790±30 BP). Silty sand layers are observed again in Unit C (30% of sand). This includes small cm-layers in Unit C1 and sandy deposits in Unit C2 over several decimetres thick. Sub-unit C3 is back to grey silty clay deposits. Interestingly, freshwater ostracods are identified at the bottom of Unit C, but brackish lagoonal deposit assemblages increase in this layer. Organic matter was dated to 4520 to 4296 cal. BP (3955 ± 30 BP) at 14.34 m b.s.l. Bedded grey sand with silty layers are deposited in Unit D with higher value for magnetic susceptibility. Magnetic susceptibility values rise slowly from 5-10 CGS to 10-20 x10 -6 CGS but never reached 100 x10 -6 CGS in Units A to C (mean value = 7 CGS). Values rise in Unit D and reach more than 1000 x10 -6 CGS in Sub-unit D2. Carbonate content is generally rising (up to 30% in Sub-unit D2) while organic matter content decreases in the sedimentary sequence. Additionally, freshwater species are more represented in the ostracods identified in Sub-Unit D1 than in the lower units. Unit D2 contains more Posidonia, and some fibers were dated to 2786 to 2686 cal. BP (2955 ± 25 BP). The harbour of Ostia is composed of compact dark grey silts mainly with freshwater ostracods. The harbour is finally sealed by coarse fluvial deposits (Unit E) and fine fluvial deposits (Unit F) (see [START_REF] Goiran | Geoarchaeology confirms location of the ancient harbour basin of Ostia (Italy)[END_REF] for a detailed description).

Fours layers were identified in Core PO-1 below the Roman harbour sequence (Fig. 10), but the core only reaches 18 m b.s.l. Grey silty clay of Core PO-1/Unit A and Unit C are most probably similar to deposits of Sub-unit B2 and C3 in Core PO-2. Surprisingly, dark coarse sand and small gravels were drilled between 15 and 17 m b.s.l. in Core PO-1. Organic matter in the layer was dated to 2715 to 2363 cal. BP (2455 ± 30 BP), but it is covered by grey silty clay in Unit C, which was dated to 4151 to 3981 cal. BP (3720 ± 30 BP) on a piece of wood laying at -14.64 m b.s.l. PO-1/Unit D corresponds to laminated grey sand similar to Core PO-1/Unit D. A similar period was obtained for these two layers with a radiocarbon date on plant material at 8.49 m b.s.l. in Core PO-1/Unit D (2845 to 2748 cal. BP, 2670 ± 30 BP). A similar harbour sequence was obtained in Cores PO-1 and 2.

Core OST-4 [START_REF] Hadler | Temple-complex postdates tsunami deposits found in the ancient harbour basin of Ostia (Rome, Italy)[END_REF] reveals the upper part of the natural sedimentary sequence that was truncated by harbour excavation during the Roman Republic period, between 2400 and 2100 cal. BP (Units E in cores PO-1 and 2) (Fig. 10). Medium sands are still observed in Unit A and still dated between 2800 and 2500 cal. Finally, between 21.30 and 12 m b.s.l., Core MO-2 reveals Early Holocene deltaic deposits settled before the development of the palaeomeander of Ostia between 2400 to 1700 cal. BP (Figs. 8 and9). The upper 12 m are described in detail in [START_REF] Salomon | Long-Term Interactions between the Roman City of Ostia and Its Paleomeander, Tiber Delta, Italy[END_REF]. The oldest radiocarbon dates of the area are recorded in Unit B and C and covered the period between 8500 and 7900 cal. BP. Unit A (21.30-19.39 m b.s.l.) is mainly composed of silt and clay (56%) with high content of sand (43%).

The organic content is only 3% (loss-on-ignition). The macrofauna is particularly interesting. Shells of Zonites nitidus were observed, which usually live along shores of lakes and riverbanks. Oxychilidae sp.

were also identified, which live in terrestrial contexts in wet environments, generally near lakes. In Unit E, very coarse pebbles were recorded at the bottom with black coarse to very coarse sand. These deposits are the coarsest ever recorded in a Middle/Late Holocene channel of the Tiber in the delta (coarsest pebbles are 2.5 cm (A-axis) × 2 cm (B-axis) × 1 cm (C-axis)). Unit F is an intercalation of sand and grey silty clay deposited in the Roman period. Finally, unit G is sub-modern deposits of grey silty clay.

DISCUSSION

Interpretation of the depositional systems

The study area considered in this paper straddles the inner and the outer delta plain. It crosses part of the palaeolagoon and the area of the archaeological site of Ostia (Fig. 2). Fig. 10 presents a synthetic cross section interpreting the depositional systems of the studied cores. Core LOA-1 studied in [START_REF] Vittori | Palaeoenvironmental evolution of the ancient lagoon of Ostia Antica (Tiber delta, Italy)[END_REF] is located in the inner deltaic plain and all other studied cores are located in the outer deltaic plain. Sandy deposits identified at the bottom of Cores PO-2 (Unit A) and MO-2 (Unit B) and Unit B in Core LOA-1 are issued from a transgressive sandy coast. Several 14 C and OSL dates confirm that Unit A / Core LOA-1 goes back from the Pleistocene (Vittori et al. in prep.). Units D in Cores PO-1 and PO-2, Unit C in Core CAT-3, Units A, B, C, D, E in Core CAT-2, and Unit D in Core MO-2 are shallowing upward successions related to the progradational delta front.

Fine marine sediments deposited in the prodelta are observed in Core PO-1 / Units A and C, Core PO-1 / Units B and C, Core CAT-3 / Unit B, and Core MO-2 / Unit C.

Transitions between these three depositional systems can also be observed. The location of Core PO-2 is the most seaward and the core better records changes in its stratigraphy. The fine interstratification of sand and silty clay in Sub-unit B1 demonstrates change from the transgressive sandy coast (Unit A) to the prodelta (Sub-unit B2). It demonstrates a normal regression of the coastline during the TST. The sandy layers within the grey silty clay in Core PO-2/Unit C corresponds to the transition between the prodelta to the delta front. It is the distal delta front part of the progradational system during the HST.

Based on our data, the switch from TST to HST, called the maximum flooding surface (mfs), is not always easy to locate precisely. According to the chronostratigraphy, it seems to happen in the Prodelta in Core PO-2 (Sub-unit B2 -Fig. 4). More analyses would be necessary to identify a slower rate of deposition and a condensed layer of fauna (condensed section). In Core CAT-3, the mfs could be on top of Unit B or not reached by the core. A deeper core, bioindicators, and additional dates would have helped to define it better (e.g., condensed section, sediment starvation, hiatus). The abrupt deepening facies in Core MO-2 / Unit C (marine grey silty clay) is covered by a small layer characterised by sediment starvation. It is expressed by high macrofaunal density (hiatus) and can be associated to the mfs (Fig. 8). Finally, the mfs in Core LOA-1 is probably at the limit between Unit B and C. Late Holocene lateral fluvial mobility removed part of the delta front deposits of the HST in Cores MO-2 (Sequence 2 -Palaeochannel -Units E, F G) and CAT-1 (Sequence 2 -Palaeochannel/Harbour -Units D and E). In addition, the excavation of the harbour of Ostia during the Roman period also removed progradational sands of the HST in Group 1 area (2400-2000 cal. BP in PO-1 and PO-2 Units E).

In the interpreted cross section between groups 1 and 4, there is currently no clear evidence of fault activity. Deeper cores and complementary dates in the stratigraphies would be necessary to interpret the sequences to examine this further.

From the TST to the HST: use of the interpretative PADM chart for single core interpretations

According to the PADM charts of Cores PO-2 (Fig. 5), Core CAT-3 (Fig. 7) and Core MO-2 (Fig. 9), the stratigraphies overlap the end of the Transgressive phase and the Progradational phases until 2500 cal. BP. Amongst the analysed cores, the transgressive coastal sand is only dated in Core MO-2. The sedimentation rate in Units B and C seems to roughly follow the rate of the modelled local sea level curve between 9000 and 8000 cal. BP, which would confirm the validity of the modelled curve of [START_REF] Lambeck | Sea level change along the Italian coast during the Holocene and projections for the future[END_REF]. It should be noticed that these four dates at the bottom of Core MO-2 dates sediments from periods often lacking in deltaic sequences or displaying a change of the facies (River deltas worldwide: [START_REF] Stanley | Worldwide Initiation of Holocene Marine Deltas by Deceleration of Sea-Level Rise[END_REF]Po delta: Amorosi et al., 2017 and[START_REF] Bruno | Late Quaternary aggradation rates and stratigraphic architecture of the southern Po Plain, Italy[END_REF] Rhine delta: Hijma andCohen, 2011, 2019;Asian deltas: Hori and Saito, 2007;Mississippi delta: Yu et al., 2012). The period 9000-8500 cal. BP is characterised by facies changes related to a sea level jump in Asian deltas [START_REF] Hori | An early Holocene sea-level jump and delta initiation[END_REF]. This change is characterised by a shift from coastal/estuarine sand or mud to prodelta mud. A sea level jump would also occur later between 8500 and 8200 cal. BP, possibly in two phases according to the data from the Rhine delta [START_REF] Hijma | Holocene sea-level database for the Rhine-Meuse Delta, The Netherlands: Implications for the pre-8.2 ka sea-level jump[END_REF]. The marine silty clay from MO-2 / Unit C could be related to a rapid deepening facies similar to the observations made by Hory and Saito (2007) for Asian deltas. The modelled curve of [START_REF] Lambeck | Sea level change along the Italian coast during the Holocene and projections for the future[END_REF] for the Tiber delta is correct, but too smoothed to show these sea level jumps. Core MO-2 / Unit C offers sedimentation for the period between 9000 and 8000 cal. BP. To support such a sediment rate in a deeper context, the sediment load transported by the Tiber River was probably very important. This strong sedimentation (sandy and fine) could be linked to the Sapropel S1 deposits in the Tyrrhenian Sea (9500-6600 cal BP in [START_REF] Emeis | Temperature and salinity variations of Mediterranean Sea surface waters over the last 16,000 years from records of planktonic stable oxygen isotopes and alkenone unsaturation ratios[END_REF]8900-7300 cal. BP in Zanchetta et al., 2007;10,800-6100 cal BP in De Lange et al., 2008). On top of Unit C, sediment starvation occurs with a hiatus (mfs). The sedimentation rate probably stopped to be consistent with the relative sea level rise, but the chronology is lacking.

At the beginning this sea level jump period, Core M0-2 shows very quickly changing environments from freshwater and terrestrial context in Unit A to a protected environment with high marine influence in Unit C, intercalated with two units of coastal sand in Units B and D. Terrestrial, freshwater, coastal and marine palaeoenvironments seem to be very close, suggesting a high mobility of the coastline and closely controlled by the rising sea level. Unit A can be associated to a coastal lake or an estuarine environment.

The upper part of Core MO-2 shows a channel-fill sequence (Sequence 2) related to the activity (2400 cal. BP and 1557 CE) and the infill of the palaeomeander of Ostia (1557 CE to the reclamation in the Late nineteenth/ Early twentieth century CE - [START_REF] Salomon | Long-Term Interactions between the Roman City of Ostia and Its Paleomeander, Tiber Delta, Italy[END_REF]. Cores S6 and S1 in [START_REF] Bellotti | The Tiber river delta plain (central Italy): Coastal evolution and implications for the ancient Ostia Roman settlement[END_REF] and Cores E, D and A farther south in [START_REF] Bellotti | Late Quaternary landscape evolution of the Tiber River delta plain (Central Italy): new evidence from pollen data, biostratigraphy and 14C dating[END_REF] demonstrate that sandy deposits continued to be deposited in the upper sequence of Core MO-2 before their removal by the palaeomeander.

The grey silty clay deposits of Core CAT-3 / Unit B are dated from 6858 to 6677 cal. BP. Unit B could be just before or contemporary with the transition from the TST to the HST (mfs). A deeper core and complementary analyses would be necessary to identify the mfs. In Fig. 7, two hypothetical sedimentation rates are proposed between Unit A and B. Unit A is either related to the transgressive coast or an instability of the delta front during the TST-HST transition. Unit B is possibly a condensed prodelta layer with a low sedimentation rate (mfs facies similar to Unit B2 in Core PO-2).

The stratigraphic sequence of Core PO-2 records both the transition from the delta front to the prodelta during the transgression phase, and the transition from the prodelta to the prograded plain after the sea level rise slows down around 7000 yr ago. The coastal sands identified at the bottom of Core PO-2 might coincides with dates obtained in the TST deposits inland, pre-dating 7000 cal. BP. No dates are available for Unit A but we estimate that these transgressive coastal sands were deposited around 10,000 and 9000 cal. BP relying on the local sea level curve proposed by [START_REF] Lambeck | Sea level change along the Italian coast during the Holocene and projections for the future[END_REF]. Sub-unit B1 shows the transition from the delta front (Unit A) to the prodelta (Unit B and C) while the coastline should be moving towards the east near Core MO-2 (retrogradation). The water-filled space (accommodation space) expands quickly right after the coastline in Core PO-2 is transgressed, but tends to reduce when the sea level rise slows down and the progradation occurs.

Even if part of the slow sedimentation observed in Units B and C is because of compaction, such geometry and temporal evolution are expected in this geomorphological context. The mfs facies might also occur during this period (Unit B2). Units B to D expose the transition from the prodelta to the delta front while the Tiber delta plain is prograding. Sub-unit C1 records the first sandy layers since Sub-unit B1 was deposited in the Early Holocene. Interestingly, freshwater ostracods species were identified in Sub-unit C1 along with brackish, coastal, and marine species. According to these palaeoenvironmental data and chronology obtained, a prograding palaeoriver mouth of the Tiber was most likely not far from Core PO-2 between 4500 and 4200 cal. BP. However, a stronger delta front influence is recorded just afterwards in Sub-unit C2. The delta front definitely progrades towards PO-2 between 4000 and 2500 cal. BP according to Unit D. The higher sedimentation rate in the upper level of Unit C and Unit D is probably because of less compaction but also to local factors linked to the closer coastline and adjustment of the slope of the delta front. This Sub-unit C2 could be related to the period of drier conditions between 4300-3800 cal. BP with intercalated phases of increased moisture recorded in lakes from Central Italy [START_REF] Magny | Holocene climate changes in the central Mediterranean as recorded by lake-level fluctuations at Lake Accesa (Tuscany, Italy)[END_REF][START_REF] Magny | Possible complexity of the climatic event around 4300-3800 cal. BP in the central and western Mediterranean[END_REF][START_REF] Magny | Contrasting patterns of precipitation seasonality during the Holocene in the south-and north-central Mediterranean[END_REF][START_REF] Sadori | Mid-Holocene vegetation history of the central Mediterranean[END_REF]. Similar progradational phases are also recorded in the Ombrone River delta [START_REF] Bellotti | Morphosedimentary characteristics and Holocene evolution of the emergent part of the Ombrone River delta (southern Tuscany)[END_REF]. Anthropogenic factors, especially stronger human impact in the watershed, also most likely affected this coastal progradation from 4400 cal. BP (Bronze Age [START_REF] Magri | Late Quaternary vegetation history at Lagaccione near Lago di Bolsena (central Italy)[END_REF][START_REF] Sadori | Mid-Holocene vegetation history of the central Mediterranean[END_REF].

More ostracods usually living in freshwater were observed in Unit D suggesting closer river influence in this coastal area. According to Core OST-4 [START_REF] Hadler | Temple-complex postdates tsunami deposits found in the ancient harbour basin of Ostia (Rome, Italy)[END_REF], the area of Core PO-2 definitely turns into the subaerial deltaic plain between 2.8 k and 2.5 k cal. BP.

Integrated age-depth model and interpretations

Fig. 11 is a synthesis of all of the apparent sedimentation curves from the cores drilled along the studied cross section from the archaeological site of Ostia to the palaeolagoon. This diagram integrates all of the PADMs presented above. Subsidence may have affected the sedimentation curve of the Outer subzone (Group 1) more than the curves of Inner subzone (Group 2 and 3), because of a deeper Holocene sequence to the west (see the unconformity at the base of the Tiber Depositional Sequence - [START_REF] Milli | The transition from wave-dominated estuary to wave-dominated delta: The Late Quaternary stratigraphic architecture of Tiber River deltaic succession (Italy)[END_REF] and the thicker fine prodelta deposits recorded in Cores PO-1 and 2. However, despite the lack of dates at the bottom of each core, this chart confirms the succession of transgressed coastlines from west to east. The first coastline to be transgressed is in Group 1 (Core PO-2 -Outer subzone), then Group 2 (Core CAT-3), and finally Group 3 (Core MO-2 -Inner subzone).

Consequently, the apparent accommodation space for the Outer subzone is deeper than for the Inner subzone between 8000 and 3000 cal. BP. This difference is also partly related to a higher subsidence in the Outer subzone. The apparent sedimentation rate is very low between 8000 and 4000 cal. BP in the Outer subzone, and accelerates since 4000 cal. BP to the definitive progradation of the Outer subzone (Group 1) around 2800-2700 cal. BP. This quicker sedimentation rate observed from 4000 cal. BP can be related to the lower compaction of these sandier layers, but also to delta front progradation in the Outer subzone. Additionally, it can also be a response to the aridification and stronger erosion happening across the Mediterranean since 4.2 k cal. BP.

The apparent sedimentation curves in the upper parts are a combination by groups of cores.

Several radiocarbon dates were rejected to produce coherent sedimentation curves for each group and are crossed out on the diagram. Deepest and more recent radiocarbon dates were generally selected to plot the sedimentation curve (especially for Cores CAT-2 and 3). When dates were very close in date and depth, we combined them within the sedimentation curve (Cores PO-1, PO-2 and OST-4). However, for the deepest date performed in Core PO-1 / Unit B we adopted a different strategy because of the possible effect of the river, and two scenarios may be considered for now (see discussion below). In any case, it results in a meeting of the sedimentation curves of Groups 1 and 2 around 2.8-2.5 k cal. BP. This observation confirms the quick progradation happening at that period [START_REF] Salomon | Geoarchaeology of the Roman port-city of Ostia: Fluvio-coastal mobility, urban development and resilience[END_REF]. Unfortunately, the HST coastline related to Core MO-2 is not known because of the erosion of the sediment from the upper part of the core by the palaeomeander of Ostia.

Considering (1) the succession of transgressed coastline from west to east observed in the integrated age-depth model (retrogradation), (2) the slower sedimentation in the prodelta comparing to the delta front, and (3) the sandy deposits reaching the modelled sea level curve during the HST (progradation), the model proposed fits into theoretical trends expected from a Holocene transgressed/prograded coast (see also [START_REF] Stanley | Worldwide Initiation of Holocene Marine Deltas by Deceleration of Sea-Level Rise[END_REF][START_REF] Tamura | Temporal development of prograding beachshoreface deposits: the Holocene of Kujukuri coastal plain, eastern Japan[END_REF][START_REF] Tanabe | Holocene evolution of the Song Hong (Red River) delta system, northern Vietnam[END_REF]. The PADM chart seems relevant to identify evidence to reconstruct coastline-trajectories. The distinction between the apparent sedimentation curve of Groups 1, 2, and 3 might be amplified by the effect of compaction, but does not reassess the model proposed. Additionally, no strong chronotopographical inversions suggest faulting activity below Ostia. This is confirmed by the fact that the dates in the lower part of Core MO-2 match the trend of evolution of the modelled local sea level curve. This approach considering geomorphological processes and their effect on sedimentation could contribute to improve decompaction methods for Late Pleistocene / Holocene deltaic sequences.

Fluvial bedload-derived facies within coastal sand near Ostia

The cross section presented in Fig. 10 shows the presence of facies interpreted such as fluvial bedload-derived deposit in very different palaeoenvironmental contexts: (1) in the prodelta in Core PO-1/Unit B; (2) in the progradational delta front in Core MO-2 / Unit E, CAT-3 / Unit D; and (3) in the Roman harbour in Core PO-1 and 2 -upper part of Units E. The bedload-derived facies of the Tiber River in its delta results in a distinct facies, composed of medium/coarse black sand with gravels and pebbles. Similar bedload-derived facies were also found in the Roman Portus canals [START_REF] Salomon | A harbourcanal at Portus: a geoarchaeological approach to the Canale Romano: Tiber delta, Italy[END_REF](Salomon et al., , 2016b) ) and in Core ISF-1 at the river mouth of the Tiber between 2500 and 2000 cal. BP [START_REF] Salomon | Geoarchaeology of the Roman port-city of Ostia: Fluvio-coastal mobility, urban development and resilience[END_REF]. Indirect fluvial influence is recorded on the coast and in the palaeolagoon with bioindicators such as ostracods and macrofauna. For information, the current maximum depth of the Tiber channel in the delta can reach 12 m [START_REF] Castellano | I rilievi topografici dell'alveo del Tevere nell'area metropolitana romana[END_REF].

Initially, only coarse fluvial deposits from fluvial bedload-derived facies were assured to be found in the palaeomeander of Ostia (Core MO-1, 2 and 3). The aerial photography taken in 1911 by balloon and sixteenth-seventeenth century texts and maps clearly revealed the position of the palaeomeander cut-off in 1557-1562 CE [START_REF] Shepherd | Il "Rilievo Topofotografico di Osita dal Pallone[END_REF][START_REF] Pannuzi | Il Castello di Giulio II ad Ostia Antica, Documenti di archeologia postmedievale[END_REF]. Other bedload-derived deposits were drilled by chance since Core CAT-2 was covered by a thick archaeological layer within the Roman city of Ostia. The fluvial harbour of Ostia was supposed to reveal only fine harbour muds, and only fine prodelta deposits were expected in the lower part of Core PO-1.

The bedload-derived facies of Unit B from Core PO-1 is related to a strong progradation in either 4000 cal. BP or around 2800-2700 cal. BP. The date of this fluvial deposit depends on the acceptance or the rejection of the date of 2715-2365 cal. BP dated on organic matter sampled in this unit. First, it was quite surprising to identify two meters of coarse fluvial deposits between 15 and 17 m b.s.l. between two units of grey silty clay. This seems to be related to a quick and strong fluvial event. Second, Core PO-2 (located only 20m away from Core PO-1) does not record a similar deposit.

However, in Core PO-2 / Sub-unit C1 around 15 m b.s.l. combined with the sandy layers deposited in the prodelta, few ostracods characteristic of a freshwater environment were identified. Third, the date of the bedload influx is similar to the quick progradation of 2800-2700 cal. BP recorded at the mouth of the Tiber delta [START_REF] Salomon | Geoarchaeology of the Roman port-city of Ostia: Fluvio-coastal mobility, urban development and resilience[END_REF], but the date just on top could be related to the 4.2 k BP event [START_REF] Magny | Holocene climate changes in the central Mediterranean as recorded by lake-level fluctuations at Lake Accesa (Tuscany, Italy)[END_REF][START_REF] Sadori | Mid-Holocene vegetation history of the central Mediterranean[END_REF]. Consequently, if the date is rejected, this bedloadderived deposit in PO-1 / Unit B could be attributed to 4500-4000 cal. BP and be coeval with PO-2 / Unit C. Alternatively, if the date of 2715-2363 cal. BP is accepted, this bedload-derived deposit would be part of the major change happening at the mouth of the Tiber River at 2800-2700 cal. BP.

The very coarse material issued from the bedload-derived deposit in the palaeomeander of Ostia in Core MO-2 / Unit E was supposed to originate from the Ponte Galeria formation upstream of the Tiber delta and brought by a strong flood event [START_REF] Salomon | Long-Term Interactions between the Roman City of Ostia and Its Paleomeander, Tiber Delta, Italy[END_REF]. The re-interpretation of the lower part of Core LOA-1 / Unit A suggests that it could also belong to outcrops of Pleistocene deposits buried a few metres below the palaeolagoon of Ostia (Vittori et al. in prep.). Some pebbles from the Pleistocene outcrops could have been more locally eroded and trapped in the pool drilled in MO-2. The bedload-derived deposit found in Core CAT-3 / Unit D is related to the palaeodynamic of the same palaeomeander of Ostia [START_REF] Salomon | Geoarchaeology of the Roman port-city of Ostia: Fluvio-coastal mobility, urban development and resilience[END_REF]. More surprising are the coarse deposits settled high over the sediment of the harbour of Ostia [START_REF] Goiran | Geoarchaeology confirms location of the ancient harbour basin of Ostia (Italy)[END_REF]. Their deposition in such a position could suggest shoals at the mouth of the Tiber River around 2000 cal. BP.

Tiber river mobility in the Tiber delta during the last 6000 years cal. BP

The last figure is a map of the lateral mobility of the Tiber River during the last 6000 yr in its delta with data available for now (Fig. 12). This timespan covers most of the period of the HST and the progradation of the Tiber delta. Several data have been collected to produce this map : (1) beach ridge and fluvial features observed in satellite imagery, old aerial photography, and geophysical surveys [START_REF] Keay | Portus : An Archaeological Survey Of The Portus Of Imperial Rome, Archaeological Monographs of the British School at Rome[END_REF][START_REF] Keay | Portus and its Hinterland: Recent Archaeological Research, Archaeological Monographs of the British School at Rome[END_REF]; and (2) stratigraphic sequences with coarse fluvial deposits. Only the upper 30 m of the cores were considered. Beach ridge features are important data because they express progradation phases not removed by river mobility. The limit of this indicator is in cases of strong coastal erosion. In this case, stratigraphic sequences can be of great help. This dataset is completed by the new data published in this paper.

Recently, several papers suggested the existence of a palaeochannel of the Tiber below the Roman harbour of Portus between 3000 and 2400 cal. BP and a strong avulsion towards the south [START_REF] Giraudi | Late Holocene evolution of Tiber river delta and geoarchaeology of Claudius and Trajan Harbor, Rome[END_REF]. However, for now no clear evidence of bedload-derived deposits supports such a hypothesis. Data from Cores PO-1 and 2 demonstrate that a branch of the Tiber River in the southern side of the delta existed since 4500-4000 cal. BP. Nevertheless, an area void of surficial features and sedimentary drilling remains between the southern part of the International airport of Fiumicino and the north of the harbour of the Roman emperor Trajan (Fig. 1).

Most of the coarse fluvial deposits identified in the upper 30 m of the cores were drilled in the northern part of the Palaeolagoon of Ostia and the current Tiber [START_REF] Bellotti | Late Quaternary landscape evolution of the Tiber River delta plain (Central Italy): new evidence from pollen data, biostratigraphy and 14C dating[END_REF]. Cores drilled at Ostia, especially Cores CAT-2 and CAT-3, expose a clear southern limit for the fluvial mobility of the Tiber during the Late Holocene. Less clear is the central and southern part of the palaeolagoon of Ostia. Finally, a recent magnetic survey conducted in the Isola Sacra revealed fluvial features in the southern part [START_REF] Germoni | Ostia beyond the Tiber : recent archaeological discoveries in the Isola Sacra[END_REF]Keay, Strutt et al. in prep.). A migration of the Tiber from the middle of the Isola Sacra to Ostia could have occurred in the between 2800 and 1700 cal. BP. During the last 2000 yr, the lateral mobility of the Tiber in the new prograded delta plain was mainly constrained along the Fiumara. The main change seems to be related to the cut-off of the Tiber River near Ostia and the construction of the Roman canals, including the Fiumicino.

Conclusion

This paper demonstrates that PADM charts (Palaeoenvironmental Age-Depth Models) are very well adapted to interpret deltaic stratigraphic sequences and to distinguish transgressive and progradational sequences. During the Early Holocene, the transgression of the coastline from east to west is clearly observed in the studied cross section. Single and combined PADM charts for different group of cores also expose the different progradation phases affecting the Tiber delta. The integration of different apparent sedimentation curves in a single age-depth model demonstrates the effect of the the sedimentation context (e.g., higher sedimentation rates in the delta front comparing to the prodelta) and clearly expose the succession of trangressed and prograded coastlines during the Holocene. It gives clear evidence to reconstruct coastline-trajectories. This integrated model could contribute to adjust decompaction methods for deltaic sequences.

Within the PADM chart, fluvial mobility makes the interpretations more complex. River dynamics erode part of the coastal stratigraphic sequences. Nevertheless, the PADM chart produces a clear view of the palaeoenvironmental context in which fluvial sediments are deposited (prodelta/deltafront, incision/deposition). It also exposes the relation between the fluvial deposits and the modelled sea level curve. Indirect evidence of fluvial activity based on bioindicators (freshwater influence) recorded in the prodelta or delta front are very informative. They suggest that the Tiber flowed towards the south of its delta from 4500-4200 cal. BP. Additionally, the Tiber bedload-derived facies recorded in the prodelta reveals complex depositional processes and interplays between the river and the delta formation.

The reconstruction of the coastal and fluvial mobility in deltaic contexts during the Holocene remains a difficult task. The reconstruction of the Holocene relative sea level curves remains one of the most important data in producing reliable interpretations. A more detailed and less smoothed modelled relative sea level curve is essential and would bring more reliable interpretations. This is particularly true to study the consequence of the sea level jumps between 9000-8000 cal. BP on coastal depositional contexts. Archaeological remains of Ostia and neighboring structures (white lines) are reported along with the main geo-features identified in this area of the Tiber delta (strandlines, fluvial ridges and swales, and the location of the palaeolagoon of Ostia according to Amenduni, 1884) Figure 3. -Reconstructed relative sea level curves and best estimations at local, regional and global scales for the Holocene [START_REF] Lambeck | Sea level change along the Italian coast during the Holocene and projections for the future[END_REF][START_REF] Lambeck | Sea level and global ice volumes from the Last Glacial Maximum to the Holocene[END_REF][START_REF] Vacchi | Multiproxy assessment of Holocene relative sea-level changes in the western Mediterranean: Sea-level variability and improvements in the definition of the isostatic signal[END_REF]. The modelled eustatic and glacio-hydro-isostatic prediction for the Tiber delta will be used [START_REF] Lambeck | Sea level change along the Italian coast during the Holocene and projections for the future[END_REF]. et al., 2014;[START_REF] Vittori | Palaeoenvironmental evolution of the ancient lagoon of Ostia Antica (Tiber delta, Italy)[END_REF][START_REF] Salomon | Long-Term Interactions between the Roman City of Ostia and Its Paleomeander, Tiber Delta, Italy[END_REF][START_REF] Salomon | Geoarchaeology of the Roman port-city of Ostia: Fluvio-coastal mobility, urban development and resilience[END_REF] Figure 11. -Synthetic PADM chart for the final transgression phase and progradation until the Roman period. Sedimentation curves were merged into three studied area: Group 1 in green -Roman harbor area (Cores PO-1, PO-2 and OST-4); Group 2 in yellow -Area of the Castrum of Ostia (Cores CAT-2 and 3); and Group 3 -Area of the lobe of the palaeomeander of Ostia (Core MO-2). This diagram show evidence to reconstruct coastline-trajectories.

Cores

  PO-2, CAT-3 and MO-2 are described in detail (Figs. 4 to 9), and observations in the other cores are used as supporting information. The upper sequences above the bold erosional boundaries lines in Fig. 10 are already published: PO-2 in Goiran et al. (2014) and Sadori et al. (2016) (Harbour of Ostia Sequence); CAT-3 in Salomon et al. (2018) (stratigraphy of a palaeochannel of the Tiber River); and MO-2 in Salomon et al. (2017) (stratigraphy of a palaeochannel of the Tiber River).

  BP at 2.30 m b.s.l. (2752 to 2547 cal. BP / 2562 ± 19 BP). Unit B is a fine deposit of grey silt dated to 2326 to 2157 cal. BP (2229 ± 17 BP) and covered again by sand in Unit C. Core CAT-3 reaches 16 m b.s.l. (Figs. 6 and 7). Laminated silty fine sands are drilled at the bottom in Unit A. Almost 1 m of grey silt is deposited in Unit B, with low magnetic susceptibility (<10 x10 -6 CGS). Some ostracods were observed in this unit and are associated with brackish environments (Cyprideis torosa) or environments without freshwater (Palmoconcha turbida, Leptocythere sp., Costa batei). Charcoals trapped in this protected environment are dated to 6858 to 6677 cal. BP (5985 ± 30 BP). From 13.5 to 6.5 m b.s.l., Unit C is composed of laminated silty sand and the upper part is dated to 3717 to 3573 cal. BP (3400 ± 30 BP). Magnetic susceptibility rises slowly from the bottom to the top of this unit. Sands are mainly fine. Comparatively, these laminated sands are more sorted and finer than in Core PO-2. Ostracods were identified at the bottom of these units and indicate a coastal environment with freshwater influence (Palmoconcha turbida, Costa batei, Pontocythere turbida). An important change in the grain size occurs at 6.51 m b.s.l. Unit D is 1 m thick and composed of 15% to 40% of coarse material. This unit is then covered by almost 3 m of silts (Unit E). Heterometric anthropic material constitutes the upper unit F.The core sequence of CAT-2 is only reaching 8 m b.s.l.[START_REF] Salomon | Geoarchaeology of the Roman port-city of Ostia: Fluvio-coastal mobility, urban development and resilience[END_REF], but reveals the upper sedimentation eroded by fluvial mobility between 2800 and 2200 cal. BP in Core CAT-3. Units B and C in CAT-2 are finer deposits in between medium sand in Units A, C and E. Four radiocarbon dates are distributed from the bottom to the top of this stratigraphic sequence. In Core CAT-2 / Unit B two radiocarbon dates (4151 to 3981 cal. BP -3720 ± 30 on organic matter -and 3333 to 3135 cal. BP -3365 ± 30 BP on Posidonia) include the time span of the last date obtained in the upper part of Core CAT-3 / Unit C (3717 to 3573 cal. BP).

  Other terrestrial species were observed like Mediterranea depressa or other gastropods. No ostracods were identified. The magnetic susceptibility is low, around 10 x10 -6 CGS on average. However, magnetic susceptibility rises in Unit B correlatively with the grain size. Unit B is composed of very well sorted sand with very low organic matter content (1%). A lot of macrofauna fragments were collected including many bivalves sp., gastropods, and other shells difficult to identify. The shells identified are mainly characteristic of sandy or rocky environments (Bittium reticulatum, Cerastoderma edule, Rissoa venusta etc.). Lentidium mediterraneum suggests a sandy/clayey bottom close to a river. A marine shell was dated at 8525-8345 cal. BP at 19 m b.s.l. (7965 ± 40 BP).Ostracods identified include Cyprideis torosa and Loxoconcha elliptica, revealing a brackish environment with high salinity variability, Loxoconcha rhomboidea, Xestoleberis nitida, Leptocythere sp. and Propontocypris cf prifera, characterising lagoonal-coastal environments (euryhaline) with low salinity changes (polyhaline), and Cushmanidea (or Pontocythere) elongata, Urocythereis possibly favosa, and Heterocythereis albomaculata, typical of a dynamic coastal environment, but with ostracods sometimes hiding in Posidonia. Similar to Unit A, deposition in a calm environment is again observed in Unit C, with 95% of silts and clay. Specific diversity reduces in this unit and only some species of Rissoa Linoelata and Bittium reticulatum living in algae, Posidonia, or rocks were observed. Some Posidonia fibers were observed at the top of this unit, which confirms marine influence in this unit. Ostracods reveal a brackish environment, indicating some contact with the sea, but not directly open to the sea (Loxoconcha rhomboidea, Xestoleberis sp., to infralittoral often with algae, Cytheridea, Paracytheridea, Carinocythereis carinata). Several dates were performed on this unit, from the bottom to the top. At 18.25 m b.s.l. a piece wood was dated to 8070 ± 40 BP and calibrated at 9125-8780 cal. BP. This date is followed at 17.15 m b.s.l. by a date on wood calibrated at 8540-8390 cal. BP (7655 ± 30 BP). In the upper part of this unit, Posidonia fibers are dated to 8525-7925 cal. BP (7545 ± 35 BP) and 8155-7965 cal. BP (7600 ± 40 BP). Lastly, laminated silty sands are deposited in Unit D. A sand content of 94% was measured at the bottom but with an average of 76% for all the samples analysed in this unit. Macrofauna exposes species from different environments, from a sandy bottom (Cerastoderma edule, Macra sp., Neverita Josephina…), or an area near the river mouth (Zonites nitidus). Ostracods reveal lagoonal-brackish (Cyprideis torosa) to marine environments (Aurila woodwardii) with coastal species (Cushmanidea elongata and Urocythereis favosa). The bottom of Unit D reveals many shell fragments. Most of the shell fragments cannot be identified. A fragment of shell was dated in this unit but should be rejected for the interpretation130 cal. BP).

Figure 1 .

 1 Figure 1. -Study area location. The map exposes the geomorphology of the Tiber delta and core

Figure 2 .

 2 Figure 2. -Location of the studied cores and other boreholes drilled in the area of Ostia.

Figure 4 .

 4 Figure 4. -Sedimentological and palaeoenvironmental analyses of Core PO-2

Figure 12 .

 12 Figure 12. -Map of the possible channel belt of the Tiber in its delta for the last 6000 yr.

Table 1 -

 1 Radiocarbon dates -calibrated with the IntCal13 curve -Reimer et al., 2013 (Materials in blue and with an asterisk are calibrated with the Marine13 curve -Reimer et al., 2013).

					Area of the palaeomeander of Ostia
	MO-1 (+1.79m)	MO-1 / 76	2.55	-0.76	Ly-8040	Organic matter	Modern	-	Modern	Modern	Salomon et al., 2017
	MO-1	MO-1 / 1143	11.43	-9.64	Ly-8041	Bone	355	25	AD 1454 to 1634	496 to 316	Salomon et al., 2017
	MO-2 (+1.7m)	MO-2 / 260	2.6	-0.9	Ly-8788	Wood	Modern	-	Modern	Modern	Salomon et al., 2017
	MO-2	MO-2 / 8.88 m	8.88	-7.18	Ly-8780	Wood	2035	30	159 BC to AD 50	2109 to 1900	Salomon et al., 2017
	MO-2	MO-2 / 9.70m	9.7	-8	Ly-8044	Wood	2160	25	356 to 112 BC	2306 to 2062	Salomon et al., 2017
	MO-2	MO-2 / 17.70 m	17.7	-16	Lyon-8807	Shell*	9370 Rejected	45	8390 to 8180 BC	10340 to 10130	New date
	MO-2	MO-2 / 17.80m	17.8	-16.1	Lyon-8042	Posidonia*	7545	35	6160 to 5975 BC	8525 to 7925	New date
	MO-2	MO-2 / 17.80m / 2	17.8	-16.1	Lyon-8043	Posidonia*	7600	40	6205 to 6015 BC	8155 to 7965	New date
	MO-2	MO-2 / 18.85 m	18.85	-17.15	Lyon-8790	Wood	7655	40	6590 to 6440 BC	8540 to 8390	New date
	MO-2	MO-2 / 19.95 m	19.95	-18.25	Lyon-8789	Wood	8070	40	7175 to 6830 BC	9125 to 8780	New date
	MO-2	MO-2 / 20.70 m	20.7	-19	Lyon-8808	Shell*	7965	40	6575 to 6395 BC	8525 to 8345	New date
	MO-3 (+2m)	MO-3 / 3.35 m	3.35	-1.35	Ly-8781	Wood	780	30	AD 1210 to 1281	740 to 669	Salomon et al., 2017
	MO-3	MO-3 / 6 to 6.05 m	6.025	-4.025	Ly-8793	Charcoal	2120	30 344 to 51 BC	2294 to 2001	Salomon et al., 2017
	MO-3	MO-3 / 10 m	10	-8	Ly-8792	Bone	2230	30	384 to 204 BC	2334 to 2154	Salomon et al., 2017

Area of the Castrum in Ostia

	CAT-1 (+3.82m)	OST-1 / 632	6.32	-2.5	Lyon-11777(SacA 40124)	Organic matter	3325	30	1687 to 1527 BC	3637 to 3477	Salomon et al., 2018
	CAT-2 (+4.34m)	OST-2 / 1150	11.50	-7.16	Lyon-11781(SacA 40128)	Posidonia*	3365	30	1383 to 1185 BC*	3333 to 3135	Salomon et al., 2018
	CAT-2	OST-2 / 1150	11.50	-7.16	Lyon-11195(SacA 37181)	Wood	6805 Rejected	30	5738 to 5638 BC	7688 to 7588	Salomon et al., 2018
	CAT-2	OST-2 / 635	6.35	-2.01	Lyon-11197(SacA 37183)	Organic matter	3220 Rejected	30	1605 to 1425 BC	3555 to 3375	Salomon et al., 2018
	CAT-2	OST-2 / 1124	11.24	-6.9	Lyon-11780(SacA 40127)	Organic matter	3720	30	2201 to 2031 BC	4151 to 3981	Salomon et al., 2018
	CAT-2	OST-2 / 885	8.85	-4.51	Lyon-11196 (SacA37182)	Organic matter	2500	30	738 to 537 BC	2688 to 2487	Salomon et al., 2018
	CAT-2	OST-2 / 613	6.13	-1.79	Lyon-11779 (SacA40126)	Wood	2530	30	797 to 543 BC	2747 to 2493	Salomon et al., 2018
	CAT-3 (+4.48m)	OST-3 / 748	7.48	-3	Lyon-11778(SacA 40125)	Charcoal	2170	30	360 to 116 BC	2310 to 2066	Salomon et al., 2018
	CAT-3	OST-3 / 780	7.8	-3.32	Lyon-11782 (SacA40129)	Wood	2190	30	361 to 178 BC	2311 to 2128	Salomon et al., 2018
	CAT-3	OST-3 / 830	8.30	-3.82	Ly-16569	Wood	2445	35	755 to 409 BC	2705 to 2359	Salomon et al., 2018
	CAT-3	OST-3 / 960	9.6	-5.12	Lyon-11783 (SacA40130)	Charcoal	2205	30	370 to 196 BC	2320 to 2146	Salomon et al., 2018
	CAT-3	OST-3 / 1110	11.10	-6.62	Lyon-11198 (SacA37184)	Charcoal	3400	30	1767 to 1623 BC	3717 to 3573	Salomon et al., 2018
	CAT-3	OST-3 / 1906	19.06	-14.58	Lyon-13721 (SacA48504)	Org. matter	5945	30	4727 BC 4908 to	6677 6858 to	New date
					Area of the Roman harbour of Ostia
	PO-2 (+2.40m)	NA	3.78	-1.38	Ly-8059 (GrA)	Wood	2040	25	160 BC to AD 25	2110 to 1925	Goiran et al., 2014
	PO-2	NA	4	-1.6	Ly-8060 (GrA)	Wood	2040	25	160 BC to AD 25	2110 to 1925	Goiran et al., 2014
	PO-2	NA	4.9	-2.5	Ly-8061 (GrA)	Charcoal	1990	25	44BC to 63AD	1994 to 1887	Goiran et al., 2014
	PO-2	NA	4.9	-2.5	Ly-8062 (GrA)	Organic matter	2050	25	164 BC to 16 AD	2114 to 1934	Goiran et al., 2014
	PO-2	NA	5.26	-2.86	Ly-8063 (GrA)	Plant material	2025	25	98 BC to AD 52	2048 to 1898	Goiran et al., 2014
	PO-2	NA	5.26	-2.86	Ly-8064 (GrA)	Wood	2050	25	164 BC to AD 16	2114 to 1934	Goiran et al., 2014
	PO-2	NA	6.045	-3.645	Ly-9096 (GrA)	Wood	2160	30	358 to 108 BC	2308 to 2058	Goiran et al., 2014
	PO-2	NA	7.035	-4.635	Ly-9095 (GrA)	Charcoal	2185	30	361 to 172 BC	2311 to 2122	Goiran et al., 2014
	PO-2	NA	8.15	-5.75	Ly-9094 (GrA)	Charcoal	2350	40	729 to 361 BC	2679 to 2311	Goiran et al., 2014
	PO-2	NA	8.53	-6.13	Ly-9093 (GrA)	Charcoal	2125	30 348 to 52 BC	2298 to 2002	Goiran et al., 2014
	PO-2	NA	8.705	-6.305	Ly-9092 (GrA)	Wood	2165	30	359 to 112 BC	2309 to 2062

Acknowledgments

We gratefully acknowledge financial and logistical support of the École française de Rome and the British School at Rome, as well as financial support from ANR-Poltevere (ANR-11-JSH3-0002) from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement n°339123. We would also like to thank the Soprintendenza Speciale Archeologia Belle Arti e Paesaggio di Roma and the Parco Archeologico di Ostia Antica. A thank you to Leah Holguin for proofreading the English text.


L Jénot

I Rouquette

J Mazières
email: mazieres.j@chu-toulouse.fr

Julien Pr

Mazières

rmr190243 R1 Fascicule vert Cas clinique Prise en charge d'un patient par traitement combiné d'une double anomalie EGFR et MET Management of a patient with a double EGFR and MET anomaly

Keywords: Non-small cell lung cancer, targeted therapy, EGFR, MET

by combined treatment.

2

Prise en charge d'un patient par traitement combiné d'une double anomalie EGFR et MET

Résumé

Introduction :

Le cancer bronchique présente certaines anomalies moléculaires dont les thérapies ciblées sont le traitement de première ligne. La mutation de l'EGFR représente 10% des CBNPC chez les caucasiens. Une amplification de MET au diagnostic associée à une mutation de l'exon 19 a été mise en évidence, alors qu'elle est habituellement décrite comme mécanisme de résistance.

Observation :

Une patiente de 74 ans, non fumeuse, a été diagnostiquée d'un adénocarcinome stade IV muté pour l'EGFR et présentant une amplification de MET. Un traitement initial par gefitinib n'a pas contrôlé la maladie. Une chimiothérapie à base de platine et pemetrexed avec une maintenance a permis une réponse. Un traitement par durvalumab pendant 27 mois a permis ensuite une stabilité carcinologique, puis du crizotinib a été mis en place, jusqu'à une nouvelle progression menant à la mise en place concomitante de crizotinib et gefitinib permettant réponse spectaculaire. La survie sans progression est de 19 mois (traitement en cours). La tolérance est satisfaisante. La tolérance est globalement bonne avec une alopécie de grade 1, une toxicité cutanée de grade 2, mais une franche amélioration de la toux, de la dyspnée et de l'état général.

La double thérapie ciblée est poursuivie avec une pathologie toujours en réponse au dernier suivi.

La survie sans progression sous double inhibition est donc de 19 mois actuellement. La survie depuis le diagnostic est à 6 ans.

Discussion

Le gène MET est impliqué dans l'oncogenèse bronchique sous différentes formes. Des mutations de l'exon 14 sont décrites de novo chez certains patients. Des amplifications sont également rapportées dans 2 situations : de novo et le plus souvent sans autres anomalie concomitante et acquis après traitement par anti-EGFR. Dans une cohorte analysant les anomalies moléculaires de 447 patients, 39 patients avaient une mutation du gène codant pour l'EGFR et aucun de ces patients ne présentait une amplification de MET initialement. Ces deux anomalies moléculaires sont fréquemment considérées comme exclusives au diagnostic [START_REF] Cappuzzo | Increased MET Gene Copy Number Negatively Affects Survival of Surgically Resected Non-Small-Cell Lung Cancer Patients[END_REF]. L'amplification de novo de MET a été montrée chez 3% des patients muté EGFR. En revanche, l'amplification de MET secondaire, apparaissant sous traitement TKI-EGFR est décrite dans 15 à 20% des CBNPC [START_REF] Ruppert | A simple view on lung cancer biology: the MET pathway][END_REF].

The Lung Cancer Mutation Consortium a mis en évidence 7 patients sur 1007 présentant une coanomalie concernant l'exon 19 de l'EGFR et MET au diagnostic. Les patients porteurs de doubles mutations impliquant l'EGFR et un autre oncogène auraient tendance à avoir un pronostic plus sombre que ceux présentant une mutation activant l' EGFR isolée [START_REF] Guibert | Characteristics and Outcomes of Patients with Lung Cancer Harboring Multiple Molecular Alterations: Results from the IFCT Study Biomarkers France[END_REF].

Les mécanismes de résistances aux anti-EGFR sont multiples sur le plan moléculaire. L'acquisition de la mutation de résistance T790M est décrite dans 50% des cas après traitement par EGFR-TKI de première ou deuxième génération. L'amplification de MET (5-21% selon les cohortes) est également décrite après TKI de première et deuxième génération et depuis peu sous osimertinib Dans notre cas, les deux anomalies moléculaires ont été mises en évidence dès les prélèvements initiaux et l'amplification de MET participait probablement à la résistance primaire sous gefitinib.

Un cas similaire de patient présentant au diagnostic une mutation de l'exon 21 de l'EGFR avec la mutation L858R traitée initialement par erlotinib a très rapidement progressé (1 mois), il a été mis en évidence secondairement une amplification de MET, il est alors décidé d'adjoindre à l'erlotinib du crizotinib, bien toléré, avec le maintien d'une réponse spectaculaire [START_REF] Li | Combination therapy of erlotinib/crizotinib in a lung adenocarcinoma patient with primary EGFR mutation plus secondary MET amplification and a novel acquired crizotinib-resistant mutation MET G1108C[END_REF]. Un autre cas décrit un patient muté initialement pour l'EGFR, ayant acquis sous erlotinib la mutation T790M impliquant un traitement par osimertinib puis une amplification de MET. L'osimertinib et du crizotinib ont été mis en association et la réponse carcinologique a été spectaculaire, et le traitement bien toléré [START_REF] York | Tolerable and Effective Combination of Full-Dose Crizotinib and Osimertinib Targeting MET Amplification Sequentially Emerging after T790M Positivity in EGFR-Mutant Non-Small Cell Lung Cancer[END_REF].

On notera également que cette double anomalie d'emblée peut correspondre à une hétérogénéité tumorale et qu'il est possible que les anomalies moléculaires de MET et EGFR soient situées sur différents sites carcinologiques de notre patiente, ne répondant pas de façon homogène au traitement.

Dans notre cas, le contrôle prolongé de la maladie sous immunothérapie (durvalumab) est inattendu si l'on se base sur les différentes données d'analyse des patients avec altération oncogénique sous immunothérapie. Que ce soit pour la mutation de l'EGFR ou MET, les inhibiteurs de points de contrôle immunitaires n'améliorent pas la survie par rapport aux thérapies ciblées. Le statut PDL1 exprimé sur 90% des cellules tumorales de notre patiente a probablement été en faveur de la stabilité carcinologique prolongée. [START_REF] Mhanna | When to Consider Immune Checkpoint Inhibitors in Oncogene-Driven Non-Small Cell Lung Cancer?[END_REF] Nous avons opté pour une combinaison avec adaptation de dose, l'erlotinib étant donné à 100 mg et le crizotinib a demi-dose : 250 mg/jour. Sous ce traitement, notre patiente présente une tolérance acceptable, les toxicités étant principalement attribuables à l'erlotinib. Les toxicités dans le cas de double thérapies ciblées sont comparables dans la littérature, sans toxicités majeures.

Comprendre les mécanismes de résistances peut faciliter la prise en charge thérapeutique, mais surtout cibler les oncogènes dans leur ensemble semble être une meilleure option thérapeutique pour le contrôle carcinologique.

A noter que de nouvelles thérapies anti MET semblent prometteuses dans le cancer du poumon. Par exemple, le capmatinib associé au gefitinib, ou le savolitinib associé à l'osimertinib ont fait preuve d'une réponse spectaculaire chez des patients présentant au diagnostic une amplification de MET et une mutation de l'EGFR.

Pour le même profil mutationnel de patient, plusieurs essais de phase I / II ont observé l'inocuité et la potentielle efficacité des antiMET (capmatinib, volitinib et tepotinib) associés à des TKI-EGFR(gefitinib, erlotinib, osimertinib) : l'essai NCT02468661 (étudiant le capmatinib associé à l'erlotinib), NCT01982955 (tépotinib associé au géfitinib), NCT01610336 (capmatinib associé au gefitinib) avec des résultats prometteurs, NCT02143466 (étude du volitinib chez les patients mutés EGFR).

Conclusion

La description de ce cas et des données de la littérature met en exergue le fait que des patients peuvent présenter dès le diagnostic la coexistence de deux anomalies moléculaires activatrices dont une mutation de l'EGFR et une amplification de MET. Les thérapies ciblées combinées peuvent alors apporter d'excellents résultats un contrôle de la maladie. Des études sur un plus grand nombre de patient devraient être réalisées.

Légende des figures

  en exergue l'intérêt d'un traitement concomitant lors d'une double addiction oncogénique. Mot clefs : Cancer bronchique non à petites cellules, thérapie ciblée, EGFR, MET Introduction La coexistence de deux anomalies moléculaires est rarement mise en évidence dans le cancer bronchique avec le panel mutationnel recherché actuellement. La recherche de mutation activatrice du récepteur de l'EGFR (epidermal growth factor receptor) est un examen de routine depuis les années 2000. Cette mutation représente environ 10% des CBNPC dans les populations caucasiennes. Les essais thérapeutiques ont permis de proposer un traitement ciblé de cette mutation dès la première ligne de traitement. [1] L'amplification de MET est décrite dans 3 à 7% des CBNPC. Cette amplification peut être décrite en tant que responsable de l'activation oncogénique ou bien en tant que mécanisme de résistance aux traitements TKI-EGFR (tyrosine kinase inhibiteur) [2]. Le crizotinib a montré son intérêt en cas d'amplification de MET [3]. Nous décrivons le cas d'une patiente présentant une mutation de l'exon 19 du gène EGFR, associée à une amplification du gène MET, résistante aux anti-EGFR et anti-MET donnés séparément mais sensible à la combinaison des 2 molécules. Observation Nous rapportons le cas d'une patiente âgée de 74 ans, non fumeuse, sans antécédent notable, prise en charge pour un adénocarcinome bronchique peu différencié initialement cT4 (par atteinte d'un nodule dans un autre lobe homolatéral) N3 (par atteinte ganglionnaire médiastinale multiple et bilatérale) M0, présentant une délétion de l'exon 19 de l'EGFR et une amplification du gène MET. Cette amplification était évaluée selon les recommandations, d'une part par immunohistochimie avec un anticorps anti-MET clone SP44 (Ventana) qui s'est avéré positif à 3+ et d'autre part par hybridation in situ en fluorescence à l'aide d'un kit de sondes double couleur MET/centromère 7 (Ventana) qui retrouvait un nombre de copie du gène MET supérieur à 6 et un ratio entre le nombre de copie du gène MET et le nombre de centromère supérieur à 1,8, qui est le seuil de positivité. La patiente a initialement bénéficié pendant 2 mois et demi d'un traitement par gefitinib, ne contrôlant pas la maladie. Face à un lâcher de ballon pulmonaire et une évolutivité médiastinale, une chimiothérapie à base de sels de platine et pemetrexed associée à du bevacizumab est initiée. L'antiangiogénique a rapidement dû être stoppé en raison d'une HTA secondaire. L'évaluation carcinologique retrouve une très nette réponse. Un traitement de maintenance par pemetrexed est entrepris. La maladie est stabilisée pendant 6 mois. La maladie progresse ensuite au niveau pulmonaire. Une rebiopsie est proposée afin d'identifier les potentiels mécanismes de résistance. La mutation EGFR initiale est retrouvée tandis que la mutation T790M est absente. L'expression de PDL1 est retrouvée dans 90% des cellules tumorales. La patiente reçoit pendant 1 an dans le cadre de l'essai ATLANTIC du durvalumab (NCT02087423), poursuivi pour une durée totale de 27 mois jusqu'à une nouvelle évolutivité parenchymateuse. Afin de mieux comprendre la biologie complexe de ce cancer, nous réalisons une analyse génomique complète utilisant le test FONDATION ONE CD. Il est mis en évidence la délétion de l'exon 19 de l'EGFR connue, l'amplification de MET mais également une mutation de p53. La charge mutationnelle est intermédiaire à 11 mutations/Megabase. Devant l'amplification de MET confirmée en FISH au laboratoire (rapport copies/centromères : 2,5), nous proposons un traitement par crizotinib 250 mg x 2/ jour après validation en RCP et hors AMM. Le crizotinib est le seul anti MET disponible. Ce traitement est bien toléré et poursuivi pendant 14 mois dans un contexte de stabilité initiale puis de progression lente. La pathologie progresse franchement au niveau hépatique et pulmonaire, associée à une altération de l'état général. La patiente est PS2 avec des douleurs abdominales, une toux et une dyspnée. Il est alors décidé après discussion en RCP moléculaire de proposer une combinaison d'erlotinib 100 mg/jr et de crizotinib 250 mg/jr afin de contrôler les deux voies oncogéniques. Ce traitement est associé à une réponse spectaculaire avec disparition des cibles hépatiques et persistances d'un minime foyer de fixation de la lésion primitive.

[ 2 ]

 2 [START_REF] Giroux Leprieur | Osimertinib (Tagrisso®) : activité, indication et modalités d'utilisation dans les cancers bronchiques non à petites cellules[END_REF].Sur le plan physiopathologique, la voie MET/HGF (facteur de croissance des hépatocytes) est une voie clé de résistance acquise contre le TKI-EGFR. La liaison du ligand HGF au récepteur MET en induit l'activation, ceci favorisant la prolifération cellulaire et la survie. Une double thérapie ciblée semble intéressante chez des patients sélectionnés.Il a été mis en évidence que malgré l'absence d'altération génomique du gène MET, son activité oncogénique est activée dans les lignées cellulaires tumorales résistantes au TKI-EGFR. De plus, l'inhibition de MET a une efficacité in vitro et in vivo sur des cellules résistantes à l'erlotinib.

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 12 Fig.1 : Coupes scannographiques thoraciques parenchymateuses