title: The rational principles of neo-adjuvant therapy for rectal cancer.
abstract: BACKGROUND
  Aim of the study is to analyze rational principles which at present govern the neoadjuvant therapy for rectal cancer and justify his application. First step is definition of targets: cellular replication block, volumetric reduction of rectal cancer, mesorectum and lateral nodes (Down staging), reduction of side-effects on close organs, radiation on more limited tissue volumes, major series of sphincter saving procedures, minor risk of microscopic tumour deposits. Second step regards standards which Protocols strive in order to: patients selection, therapeutic index, restaging before surgery, total mesorectal excision (TME). Further step accounts for evidence of drawbacks, related to Neoadjuvant approach, both Radiotherapy alone (RT) or Radiochemotherapy (CH-RT).
  
  
  METHODS
  Indications for neoadjuvant therapy, basing a difference between the absolute and relative one, are explained. Given that granting role to such therapy still now remain partially unclear, we have outlined the following topics: A) survey of main protocols is managed, taking care on dose/response ratio, focusing on enhanced supply for fixed tumours, checking on a list of several drugs (oxaliplatinum, capecitabin, raltitrexed, CPT-11, eniluracil), which are medicated with RT and furthermore on a list of substitute RT methods (HART, IORT, Endocavitary). B) following whole treatments, according such a different approaches, analysis of obtained outcomes in the literature are carried out. C) Personal experience, basing on a previous series where Down-staging has been sought, comparing indicatively clinical and diagnostic data before neoadjuvant therapy and before surgery. D) List of open issues, not solved at present, is shown
  
  
  CONCLUSIONS
  Neoadjuvant therapy may be considered a rational approach for treatment of curative rectal cancer; indeed, preliminary results seem to introduce a real advantage compared to adjuvant therapy, even if is mandatory to associate proper surgical procedure, as TME, to warrant low local recurrences. Targets, related to such therapy, may be noticed ideal even though outcomes don't come up always to statements. So, continuous efforts to ameliorate rates of free-disease series, as well mortality rates and toxical effects are advised.
authors.affiliation: Istituto di Patologia Chirurgica III, Università degli Studi di Firenze. segr-chir@dfc.unifi.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Tonelli
authors.forename: Corrado R
authors.initials: CR
authors.lastname: Asteria
authors.forename: Tommaso
authors.initials: T
authors.lastname: Marcucci
mesh_terms: D017024:Chemotherapy, Adjuvant; D006801:Humans; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*