Carbon ion therapy for patients with localized, resectable adenocarcinoma of the pancreas

Carbon ion therapy for patients with localized, resectable adenocarcinoma of the pancreas 

Category:

Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Meeting:

2005 Gastrointestinal Cancers Symposium

Session Type and Session Title:

Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract - General Poster Session

Author(s):

S. Yamada, H. Kato, K. Yamaguchi, H. Kitabayashi, H. Tsujii, H. Saisyo, Working group for the pancreas cancer

Abstract:

Background:

We examined the effect of preoperative carbon ion therapy in terms of reducing the rate of local recurrence in patients undergoing resection for adenocarcinoma of the pancreas and then reducing treatment period by using biological properties of high-LET radiations.

Methods:

Between April 2000 and August 2004, 31 patients judged at the clinical stages I,II or III were enrolled into this trial. Criteria for trial eligibility were confirmation of ductal carcinoma by CT findings. Carbon beams of 290, 350 and 400 MeV/nucleon energy were generated in the HIMAC synchrotron. Carbon ion therapy was given once daily, 4days a week, for 16 fractions in 4 weeks or 8 fractions in 2 weeks. The dose was set to 44.8GyE(2.8GyE per fraction) and escalated to 48.0GyE at 5% increments for 16 fractions or 30.0GyE(3.75 GyE per fraction) and escalated to 33.2GyE for 8 fractions. The target volume included gross tumor and regional pancreatic draining lymph nodes. Toxicity on organs such as the skin and digestive tracts was assessed according to the NCI-CTC(acute) and RTOG/EOTRC(late) classification.

Results:

No grade 3 to 5 acute toxicity was observed. Two grade3 late reactions occurred among 12 of the patients treated with a dose of 48.0GyE. All of 2 reactions were portal vein stenoses after surgery. Of 31 patients, 21(68%) had resection. The pathologic response of the 19 resected specimens revealed evidence of grade 2 treatment effects with significant fibrosis, hyalinization, and necrosis (Pathological grade2 is defined as a less than 33% active cancer cells.). Remarkable antitumor effects were observed. The overall actual local control rates were 100% and 100% at 1 year and at 2 years of follow-up respectively. No local failure was observed in any of the 31 enrolled patients. The one year overall survival rate of all enrolled patients were 61.9%, and these of patients with resection were 90.1% . None of the patients who underwent resection had local and regional recurrences. All instances of failure were distant, and all of them were in the liver.

Conclusions:

The above results suggest the superior usefulness of heavy ion radiotherapy in the treatment of pancreatic carcinoma to conventional photon radiotherapy.

International Hospital Ranking

Cancer Adoptive Cell Immunotherapy in Japan

Cell based Immunotherapy (Autologous immune enhancement therapy) has been more frequently practised in Japan.Techniques to harvest the cells are extremely intricate and delicate processes. For the treatments to be rountinely available to the cancer patients apart from the clinical trials, advanced engineering cell reprocessing center must be available with good corroboration with the hospitals.

Since Japan made the Immuno-Cell Therapy to be a part of health care systems, the cell processing centers (CPCs) rapidly increased in the past decades. For the therapy of high complexity such as dendritic cell / autologous enhancement immunotherapy to be regularly practiced in the hospital, those CPCs were essential, and this explains why much of innovations in cell based cancer immunotherapy took place in Japan. 

Endoscopic Submucosal Dissection (ESD) \ Endoscopic Mucosal Resection (EMR) in Japan

Both EMR and ESD was originally developed in Japan. EMR / ESD (endoscopic biopsy or polyp resection procedure on gastrointestinal tract) is the area that Japanese surgeons are leading the research at forefront. It is the minimally invasive endoscopic procedure that conserves organs / tissues, and patients can be discharged from the hospital in the same day or a week after the operations. It is usually applicable to early stage cancer / tumor, and improves the post-surgical health conditions such as loss of appetite, fever, chills, pains and life-long medication.

Proton Beam Therapy

Currently there are about 31 proton (or carbon ion) therapy facilities in the world, 8 of which is built in Japan. Proton Beam Therapy is much less invasive than other radiotherapy treatments, and can treat the cancer without incision of the body, and with much less side effects than X-ray treatments. Japan has invested in Proton beam therapy (PBT) / Carbon Ion Therapy infrastructure for a long time, and clinical level studies are numerous and thus well experienced with all kinds of localized tumors.

Radiofrequency Ablation (RFA) on Liver cancer (Hepatocellular carcinoma)

Japan has been leading the RFA intervention technology for a long time, and the yearly number of RFA interventions in Japan currently exceeds that of United States and China. (See the Table below.) Survival rates for the patients undergoing the RFA are not different from those of surgery. But the surgery is harder to be operated multiple times, whereas the RFA is not restricted by the number of interventions or by the presence of Hepatitis.  For this reason, RFA becomes a standard treatment in Japan.

Yearly volume of RFA on Liver Cancer
Japan 34,000
US 14,000
China 9,500

Table: Yearly number of Radiofrequency ablation of Liver or hepatic tumors by country.

Regenerative Medicine on Dilated Cardiomyopathy, or Myocardial Infarction

Recent technological advances in cell sheets engineering extended to the pre-clinical trial of the treatment of heart disease patients often in need for the heart transplant.

Micro-Catheter treatments on varicose veins (including the veins below the knee)

In japan, complex operations towards varicose veins below the knee are established with safey and high response rates. Various catheter and micro-catheter devices are extensively used, and some of them are only available in Japan.

Cancer and Heart Disease Treatment in Japan  

Medical technology in Japan for cancer screening and gastrointestinal diseases are known to be very strong, supported by good clinical statistics, i.e., high five year survival rate after the surgery (or radiology / chemotherapy) among the colon, rectal, stomach, and esophageal cancer patients as well as liver, lung, and larynx cancer (See Table below). 

Since Japanese health agency is notoriously slow and counter-productive when it comes to the approval of new drugs, Japan's hospitals and patients suffered for so long by the technology lag from the rest of the world. Ironically, these regulatory problems lead physicians to the innovations in the fields other than drug discoveries, i.e., in the surgical / laparoscopic, endoscopic, micro-catheter procedures, cell based immunotherapy / vaccinations, radiation (carbon ion and proton beam), and regenerative medicine (iPS cells, cell sheets).

Since the Japanese physicians had less options in chemotherapy, they had more opportunities in experiencing difficult surgeries, and tried the new treatments due to the low availability of new drugs. Thus, many exotic and unique medical technologies emerged out of the isolations casued by the incompetence of Japanese health agency.

Site (Survival Rate:  %)

7 Cancer Registrates in Japan

US SEER Program Eurocare-3
Esophagus 25 14 10
Stomach 58 22 23
Colon 66 62 51
Rectum 63 63 48
Liver 17 7 7
Gallbladder 18 16 12
Pancreas 6 4 4
Larynx 77 65 62
Lung, bronchus 20 15 11