title: Clinical outcomes and toxicities of proton radiotherapy for gastrointestinal neoplasms: a systematic review.
abstract: BACKGROUND
  Proton beam radiotherapy (PBT) is frequently shown to be dosimetrically superior to photon radiotherapy (RT), though supporting data for clinical benefit are severely limited. Because of the potential for toxicity reduction in gastrointestinal (GI) malignancies, we systematically reviewed the literature on clinical outcomes (survival/toxicity) of PBT.
  
  
  METHODS
  A systematic search of PubMed, EMBASE, abstracts from meetings of the American Society for Radiation Oncology, Particle Therapy Co-Operative Group, and American Society of Clinical Oncology was conducted for publications from 2000-2015. Thirty-eight original investigations were analyzed.
  
  
  RESULTS
  Although results of PBT are not directly comparable to historical data, outcomes roughly mirror previous data, generally with reduced toxicities for PBT in some neoplasms. For esophageal cancer, PBT is associated with reduced toxicities, postoperative complications, and hospital stay as compared to photon radiation, while achieving comparable local control (LC) and overall survival (OS). In pancreatic cancer, numerical survival for resected/unresected cases is also similar to existing photon data, whereas grade ≥3 nausea/emesis and post-operative complications are numerically lower than those reported with photon RT. The strongest data in support of PBT for HCC comes from phase II trials demonstrating very low toxicities, and a phase III trial of PBT versus transarterial chemoembolization demonstrating trends towards improved LC and progression-free survival (PFS) with PBT, along with fewer post-treatment hospitalizations. Survival and toxicity data for cholangiocarcinoma, liver metastases, and retroperitoneal sarcoma are also roughly equivalent to historical photon controls. There are two small reports for gastric cancer and three for anorectal cancer; these are not addressed further.
  
  
  CONCLUSIONS
  Limited quality (and quantity) of data hamper direct comparisons and conclusions. However, the available data, despite the inherent caveats and limitations, suggest that PBT offers the potential to achieve significant reduction in treatment-related toxicities without compromising survival or LC for multiple GI malignancies. Several randomized comparative trials are underway that will provide more definitive answers.
authors: 1 Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE, USA ; 2 Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA ; 3 Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA ; 4 Miami Cancer Institute, Baptist Health South Florida, Coral Gables, FL, USA.
authors: Vivek
authors: V
authors: Verma
authors: 1 Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE, USA ; 2 Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA ; 3 Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA ; 4 Miami Cancer Institute, Baptist Health South Florida, Coral Gables, FL, USA.
authors: Steven H
authors: SH
authors: Lin
authors: 1 Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE, USA ; 2 Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA ; 3 Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA ; 4 Miami Cancer Institute, Baptist Health South Florida, Coral Gables, FL, USA.
authors: Charles B
authors: CB
authors: Simone
authors: 1 Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE, USA ; 2 Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA ; 3 Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA ; 4 Miami Cancer Institute, Baptist Health South Florida, Coral Gables, FL, USA.
authors: Minesh P
authors: MP
authors: Mehta
keywords: Proton radiation therapy (PBT); anal cancer; cholangiocarcinoma; esophageal cancer; gastric cancer; liver cancer; metastases; pancreatic cancer; particle therapy; rectal cancer; retroperitoneal sarcoma