Carbon Ion Radiotherapy for Patients with Locally Recurrent Rectal Cancer and Pancreatic Cancer

The large intestine starts at the ascending colon, which is connected to the small bowel, and ends at the rectum, which extends from the sacral promontory to the anal canal. In 2008, approximately 43,000 patients died of colorectal cancer in Japan which is the third most common cause of cancer deaths, after lung and stomach cancers. Approximately 100,000 patients were diagnosed with colorectal cancer in 2004, thus making it the second most common type of cancer after stomach cancer. The analysis of the post-operative recurrence rates of colorectal cancer indicates a higher rate for rectal cancer than colon cancer. When compared by the site of recurrence, rectal cancer had a more than three times higher local recurrence rate than colon cancer.With the recent advances in surgical techniques and procedures, the pelvic recurrence rate of rectal cancer has been decreasing, however the post-operative recurrence rate is still 5% to 20% today. Surgical resection is the first choice for locally recurrent rectal cancer, although total pelvic extenteration or another highly invasive procedure is often required. In many cases, locally recurrent rectal cancers are not completely resectable so generally surgical resections are not selected. The comparison of resection rates by the type of tumors shows that the resection rates were in the range of 40% to 50% for liver metastases and 20% to 40% for lung metastases, whereas the rate was 10% to 40% for locally recurrent colorectal cancers (Table 1)1,2) Curative resection of thesetumors will lead to a survival rate similar to those for other types of recurrences and metastases.Radiation therapy is often indicated for unresectable cases of locally recurrent rectal cancer; most of the past studies on conventional x-ray radiotherapy reported a 12-month median survival and a 10% 3-year overall survival. The use of adjuvant chemotherapy elevated the local control rate up to around 20%, which is far from satisfactory. Heavy charged particle beams have been shown to exert potent anti-tumor effects against radioresistant adenocarcinomas. To improve both the long-term local control and survival of locally recurrentrectal cancer, we have initiated a radiation dose-escalation trial using heavy charged particles.\nThe number of deaths from pancreatic cancer in Japan exceeds 26,000 per year, and the number is increasing every year1. Pancreatic cancer is the fifth leading cause of cancer death and it is considered to be one of the most lethal cancers in Japan. Complete surgical resection is the only curative treatment. However, only a small percentage of patients (10-20%) are candidates for surgical resection because of local progression or metastatic spread at the time of diagnosis2, 3. Even if a curative resection is performed, the disease usually recurs and 5-year survival rates are less than 20% 4, 5. Chemotherapy or chemoradiotherapy is selected as a standard treatment for unresectable pancreatic cancer. However, since pancreatic cancer is often resistant to chemotherapy or radiotherapy, the local control rate is very low. Recently, along with the development of new anticancer agents, the irradiation techniques have greatly progressed following the introduction of highly advanced radiotherapy. However, the outcome from therapy is still not satisfactory, with the median survival being approximately 10 months6, 7. We started phase I/II clinical trial for pre-operative carbon ion radiotherapy (CIRT) with 16 fractions in 4 weeks for resectable pancreatic cancer in 2000 (Figure 1).The purpose of this treatment was to reduce the risk of postoperative local recurrence, which accounts for approximately 50% of total recurrences. We established the tolerance and effectiveness of preoperative CIRT and performed a clinical trial aimed at shortening the fraction size to 8 fractions in 2 weeks beginning in 2003 (Protocol 0203). In addition, we started phase I/II clinical trial for patients with locally advanced pancreatic cancer and showed that the treatment was safe and provided excellent local control rates. Accordingly, we are currently performing a clinical trial of using carbon ion radiotherapy combined with gemcitabine (Protocol 0513).NIRS-KFSHRC Joint Symposium on Carbon Ion Radiotherapy and Radiation Emergency Medicin