[Heavy ion therapy for non-small cell lung cancer].

Carbon beam radiation has well-balanced dual actions on cancer: efficient dose localization and potent biological anticancer effect due to high RBE (Relative Biological Effectiveness). Two phase I/II clinical studies on the carbon beam radiation treatment of inoperable stage I non-small cell lung cancer (NSCLC) were carried out in our institution from October 1996 to February 1999. The dose-limiting toxicity was found to be radiation pneumonia. In the first protocol, 47 patients received 18 fractions of increasing doses from 59.4 GyE by 10% over 6 weeks. The maximum tolerated dose was found to be 95.4 GyE, while the complete tumor control dose was 85.6 GyE. In the second protocol, 34 patients received 9 fractions of in creasing doses from 68.4 GyE by 5% over 3 weeks. The maximum tolerated dose was 79.2 GyE, and the complete tumor control dose was > 68.9 GyE. The 4-year survival rate estimated by the Kaplan-Meier method was 56% for patients receiving the first protocol. Because a higher local control rate was achieved in the second protocol, the 5-year survival rate is estimated to be higher and similar to that achieved after surgery. Another phase II clinical study in patients with stage INSCLC is ongoing. Heavy-particle radiotherapy is a new modality for the treatment of lung cancer which holds promise for the 21st century.

[Heavy ion radiotherapy for lung cancer].

In our institute, heavy ion medical accelerator in Chiba (HIMAC) completed to be constructed October, 1994. Next year, we started to treat head & neck cancer firstly as a pilot study using carbon beam. Following the observation on the expected reaction of skin and mucosa membrane, we opened the protocol for lung cancer entitled "A phase I/II and II clinical trials of heavy iron particle radiotherapy for non-small cell carcinoma of the lung". Since then, Cabon beam possessing the well-balanced dual actions on cancer: efficient dose-localization and high RBE was given to 25 inoperable patients with stage 1 and 3 patients with stage IIIA as preoperative radiotherapy. The dose was raising from 59.4GyE, 64.5GyE and 72GyE by 10%. Tumor control of the patients who elapsed more than 6 months was evaluated in two of 4 patients (50%) given 59.4GyE, one of 4 (75%) given 64.5GyE and all of 17 (100%) given 72GyE. It appeared to be dose dependent. On the other hand, two of 28 patients (7%) showed acute radiation pneumonia treated with steroid hormone. However, the late effect of the lung was weaken with slight radiographic changes and with no manifestations. Now that heavy ion particle radiotherapy for lung cancer was revealed to be safe, we intend to attain the tumor control compatible with that of surgery.

Dup 753 prevents the development of puromycin aminonucleoside-induced nephrosis.

The appearance of nephrotic syndromes such as proteinuria, hypoalbuminemia, hypercholesterolemia and increase in blood nitrogen urea, induced in rats by injection of puromycin aminonucleoside was markedly inhibited by oral administration of Dup 753 (losartan), a novel angiotensin II receptor antagonist, at a dose of 1 or 2 mg/kg per day. The results suggest a possible involvement of the renin-angiotensin system in the development of puromycin aminonucleoside-induced nephrosis.

[The value of frequent positioning of treatment field in radiotherapy of esophageal cancer].

Since 1983 a clinical trial of proton beam radiotherapy has been conducted at the Proton Medical Research Center (PMRC) of the University of Tsukuba. We have made it a rule to do field localization by X-ray pictures before each treatment. For this purpose we have developed a localize-verify system consisting of a fluoroscopic unit and a real time digital image processing device. By using this system as well as X-ray films, field placement errors or corrected distance at field localization were measured in 11 patients with esophageal cancers. Measurements of corrected distances on a total of 177 localization attempts disclosed that correction by > 5 mm was necessary in 30.6% and by > 10 mm in 10.2% of all localization attempts. Corrected distances appeared to increase with age, possibly because the skin becomes looser and ambulatory status tends to be more limited in older patients. Field placement corrections of more than 5 mm were required in 66.7% of 60 localizations in patients > 80 years old. Two patients in whom the anatomical positions of the esophagus were easily movable are presented. The following common characteristics of these patients were considered high risk factors: they were more than 80 years old; lesions were located in the lower esophagus; and they had T1 tumors. These findings suggested that frequent positioning and verification of treatment fields are necessary in the accurate treatment of esophageal cancers, especially those in high-risk patients.