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Venice to Sienna to Rome

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My sister and I (ages 60+) will be joining a group of women in Tuscany (Montisi) in October for a week. Prior to that, we're thinking of flying into Venice and spending three nights there and taking the train to Sienna for three nights. Some questions - is train the best way to get from Venice to Sienna? About how long will the train ride take? We're open to any suggestions about other places to stop. This is not our first trip to Italy. We've been to Florence, Cinque Terre and Rome and love it all, and know there is much more to see.
After our wonderful week in Tuscany, we'll take the train to Rome and have a couple of nights there before returning to the U.S. We've seen many of the sights there, but have special interest in the Vatican and St Peter's. I've heard of some special tours that have to be reserved far in advance but don't know what they are.
Thanks for any suggestions or comments you may have!

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