Module 5: Clinical Outcomes by Disease Site - The Use of Proton Therapy in the Treatment of Cancers of the Gastrointestinal System

Eric Shinohara MD, MSCI
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 15, 2009

Cancers of the esophagus

Esophageal cancer has historically been treated with a combination of surgery (when possible), photon radiotherapy, and chemotherapy. Radiation therapy doses to the esophagus are limited by nearby critical structures including the spinal cord, lungs, and heart, which can lead to acute and chronic toxicities. Dose escalation in definitive radiation treatment of esophageal cancer is somewhat controversial, as the RTOG trial had excessive deaths on the high dose treatment arm (although several of these deaths were in patients that did not receive the full radiation dose). Currently used radiation doses are associated with poor local control. Proton radiotherapy offers a way to increase the total tumor dose (and hopefully local control) without excessive toxicity for definitive radiation treatment of esophagus cancer. There are multiple studies which have demonstrated that treatment of esophageal cancers with proton therapy is feasible and with greater sparing of surrounding normal tissues and less toxicity, as outlined in the studies reviewed below.

Links to reviews of recent abstracts and presentations regarding proton therapy for esophageal cancers:

Cancers of the Pancreas

Pancreatic cancer is the fourth leading cause of cancer related death in the United States and the majority of patients present with unresectable disease. The five year survival is poor even in patients who can be resected (5 year survival ∼10%) and is even worse in patients who are unresectable (2 year survival ∼15%). Given these poor outcomes, chemotherapy and radiation can be used to improve local control and overall survival. However, there have been conflicting results regarding the efficacy of radiation in pancreatic cancer. These differences in outcome between studies may be partly due to toxicities related with treatment leading to increased breaks which compromise treatment. In order to decrease treatment related side effects, there has been a movement towards reducing treatment volumes and reducing chemotherapy doses of the most active agents in an effort to combine therapy. Proton therapy may potentially further decrease toxicity by limiting exit dose and decreasing the volume of normal tissues which receive radiation. This may allow the use of more potent or higher doses of chemotherapy concurrent with radiation as well as allow dose escalation of the radiation.

Comparative treatment planning performed at the Hospital of the University of Pennsylvania for the treatment of pancreatic cancer shows significant reductions in dose to normal structures. The tolerance of normal tissues has prevented effective dose escalation for this malignancy. Table 3 (Hsiung-Stripp DC et al. Med Dosim. 2001 Fall;26(3):255-9). shows how protons can significantly reduce the dose to normal tissues and allow for dose escalation.

Table 3. Comparison between X-ray and proton doses for pancreatic cancer


X-ray Dose (Gy)

Proton Dose (Gy)

Dose Reduction


Spinal Cord










Right Kidney





Left Kidney





Links to reviews of recent abstracts and presentations regarding proton therapy for pancreatic cancer:

Cancers of the Liver and Biliary System

Hepatocellur Carcinoma (HCC) is one of the most common cancers in Asia and the 4th leading cause of cancer death world wide. Most patients present with advanced stage and 80% are not eligible for surgery at the time of presentation. Conventional radiation therapy is difficult to administer due to the sensitivity of the normal liver to radiation which reduces the ability to deliver doses high enough to kill the HCC. Radiation induced liver damage (RILD) and destruction of large amounts of normal liver are common with conventional radiation, which has limited its utilization. Protons can significantly spare normal tissue radiation exposure and may be a viable treatment for these patients with HCC. There have been exciting preliminary studies out of China which have shown high level of both local control and overall survival at 1 year and are discussed further in the links below.

Links to reviews of recent abstracts and presentations regarding proton therapy for liver cancer:

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