Applicability of a mobile accelerator for intraoperative radiation therapy to colorectal cancer.

PURPOSE: Intraoperative radiation therapy is reportedly effective for local control and pain relief in colorectal cancer. However, this treatment requires a large number of medical personnel, which hinders expanded use of this method. A mobile electron linear accelerator for intraoperative radiation therapy has been developed and is now commercially available. This report analyzes the applicability of this accelerator to colorectal cancer. The applicability of the mobile accelerator is analyzed based on its specifications by simulating the intraoperative radiation therapy delivered to these patients with a conventional intraoperative radiation therapy unit. METHODS: From 1987 to 1999, 49 colorectal cancer patients underwent 54 surgical resections and received intraoperative radiation therapy to 75 sites. RESULTS: The mean intraoperative radiation therapy dose for colorectal cancer with the conventional unit was 22 (range, 10-30) Gy. The mean electron energy level was 10 (range, 3-30) MEV. Applicator size ranged from 4 to 10 cm in diameter. The mobile accelerator can achieve a dose rate of 10 Gy/min and an applicator unit size range of 3 to 10 cm in diameter, facilitating intraoperative radiation therapy for colorectal cancer. The electron energy limitation (12 MEV at maximum) suggests that the indications for this machine are limited. In our experience, 30 percent of patients received intraoperative radiation therapy with electron energy levels exceeding 12 MEV. Of these cases, 81 percent had macroscopic residual tumor and 69 percent had pain. CONCLUSION: An intraoperative radiation therapy mobile accelerator can cover 72 percent of the irradiation sites covered using our conventional unit. This accelerator is useful for intraoperative radiation therapy with curative intent for patients with no or slight residual tumor. Patients with gross residual tumor and pain may not be suitable.

Intraoperative irradiation after surgery for locally recurrent rectal cancer.

PURPOSE: This study retrospectively evaluated the effects of intraoperative electron beam irradiation on patients with locally recurrent (pelvic) rectal cancer. METHODS: From November 1, 1975, to December 31, 1997, 51 patients underwent surgery for locally recurrent rectal or rectosigmoid cancer, and 27 patients received intraoperative electron beam irradiation. The intraoperative electron beam irradiation dose was 15 to 30 Gy. Kaplan-Meier survival estimates at three and five years were analyzed for the 47 patients who recovered postoperatively. RESULTS: Statistically significant factors related to survival included intraoperative electron beam irradiation vs. no intraoperative electron beam irradiation (P=0.0007), amount of residual tumor (slight vs. gross; P=0.0022), and symptom status (P=0.0024). Factors not associated with survival included distant metastases at reoperation, type of surgery for the recurrent tumor, external beam irradiation, pathologic grade, age, and gender. Surgical resection without intraoperative electron beam irradiation resulted in three-year and five-year survival rates of 5 and 0 percent, respectively. For patients who received intraoperative electron beam irradiation, the three-year survival rate was 43 percent and five-year survival rate was 21 percent. Intraoperative electron beam irradiation was a statistically significant factor related to survival in patients with and without distant metastasis (P=0.04 and P=0.0035, respectively), with slight residual tumor (P=0.0003), or with palliative surgery (P=0.0276). CONCLUSION: The trends seen in resection with intraoperative electron beam irradiation are encouraging with regard to improvements in survival as compared with studies not using intraoperative electron beam irradiation treatment.

[Method for determining optimal intracavitary radiotherapy conditions for carcinoma of the uterine cervix with tumor infiltration of the vaginal wall].

Stage III carcinoma of the uterine cervix is occasionally accompanied by tumor infiltration of the vaginal wall. Currently, the vaginal wall has to be irradiated in the same manner as the uterine cervix. The authors have developed a system for determining the optimal irradiation conditions for treating the two regions, uterine cervix and vaginal wall, at the same time. A comparison of two methods is shown in simulation, and then a clinical case is reported. The first method consists of two treatment plans, one for the uterine cervix without tumor infiltration of the vaginal wall, and the other for the vaginal wall without carcinoma of the uterine cervix. The second, newly developed method considers the two regions together. Irradiation times of ovoid sources obtained with the second method are 15-25% less than those of the first method. Isodose curves obtained with the two methods are very different, and thus the uterine cervix and vaginal wall must be considered together in order to determine irradiation conditions.

[Clinical evaluation of intra-operative radiotherapy combined with subtotal cystectomy for invasive bladder carcinoma].

From 1981 to 1994, intra-operative radiotherapy after subtotal cystectomy was performed on 22 patients with invasive bladder carcinoma on whom radical cystectomy could not be recommended because of old age or condition. All the patients received 25 to 30 Gy of radiotherapy focused on trigonum and internal urethral orifice after subtotal cystectomy with uretero-cutaneostomy. Of 22 patients, 15 patients died. Five patients died of bladder cancer, one died of gastric cancer, one died of rectal cancer and the others died of pneumonia, heart failure, sepsis and senility. The five-year survival rate was 41% and the cause-specific five-year survival rate was 75%. Local recurrence was seen only in one patients, who received second intra-operative radiotherapy and recovered well in complete remission. We believe that intra-operative radiotherapy after subtotal cystectomy is useful for patients with invasive bladder carcinoma on whom radical cystectomy could not be recommended because of old age or condition.

[Techniques for determining position from more than two radiographs intersecting at arbitrary angles in brachytherapy].

The least squares method and geometrical solution for calculating position were used in the two-projection method. Five coordinate systems were defined as a normal system, image system on film intersecting the beam central axes at an arbitrary angle and the projection, virtual coordinate and virtual image coordinate systems with beam central axis as one of the three coordinate axes to determine the geometrical relationship between a point and image on the film. Normal coordinates of the point were calculated by six geometrical solution sets and two forms of the least squares method using the rotation matrixes of the coordinate systems. One least squares method solves simultaneous nonlinear equations, and the other derives a strict solution from simultaneous linear equations. The latter least squares method has little physical meaning and is not as useful as the former. Although the former has physical meaning, the iterative approximation method should be used to determine position since a strict solution cannot be obtained directly. By these least squares methods, position is determined with less error using the projections at more than two focal spots.

Hyperfractionated and hypofractionated radiation therapy for human malignant glioma xenograft in nude mice.

Xenografts of a human malignant glioma subcutaneously transplanted into nude mice were irradiated with graded single doses (2, 5, 10 or 20 Gy) or five types of fractionation schedules in two weeks: conventional [20 Gy in 10 fractions (fr)], hyperfractionated [24 Gy in 20 fr (two fractions per day)], and hypofractionated-1, 2, 3 [20 Gy, 18 Gy, 16 Gy in 4 fr]. All of the fractionated irradiation groups showed tumor regression. The hypofractionation-1 group (20 Gy in 4 fr) demonstrated the most prominent tumor regression, while the hyperfractionation group (24 Gy in 20 fr) showed the least effect. The hypofractionation-2 group (18 Gy in 4 fr) showed similar regression to the conventional fractionation group (20 Gy in 10 fr). Histologically, tumors in the control groups consisted of a homogenous population of small anaplastic cells, and only a small number of tumor cells were glial fibrillary acidic protein (GFAP)-positive. Following irradiation, the population of small anaplastic cells decreased and the percentage of GFAP-positive cells increased. Cellular pleomorphism became much more prominent after irradiation in all of the fractionated irradiation groups as compared with the graded single dose irradiation groups. In this study, hyperfractionation was not effective against human glioma xenografts compared with conventional fractionation and hypofractionation. This indicates that care is needed in applying hyperfractionation regimens to human malignant gliomas.

[Determination of source position for four radiography systems with orthogonal projections in brachytherapy].

Four configurations of two X-ray tube positions are available for determining the position of a point using two orthogonal films. For each configuration, there are many formulas for calculating the coordinate of a point: the least squares methods with and without physical meaning, such as six sets of geometrical solutions, an approximation method with constant magnifications and so on. It is troublesome for a person in charge of treatment planning to directly derive a formula or select an appropriate formula from numerous ones for the four configurations. Thus, a method to easily apply the published formula for a configuration to the other three configurations is described in simulations and a clinical case using rotation matrixes of the right-handed coordinate system. Each diagonal element of the rotation matrixes is 1 or -1, and the other elements are 0.

[Determination of the point position for brachytherapy from the shift-projection method using the least squares method and geometrical solutions].

We have derived formulas by the least squares method and six sets of geometrical solutions for calculating the position for brachytherapy from shift-projection images on one or two films. There are four types of expression for each coordinate in both methods, the shift-film technique with double exposures on a film and the stereo-shift technique with two films. Some geometrical solutions for the shift-film technique are equal to well-known conventional formulas. In the case of the stereo-shift technique, each conventional formula for the two coordinates is equal to the mean of the two geometrical solutions of each coordinate, and the one for the other coordinate is equal to one of the geometrical solutions. Formulas for the shift-film technique can be easily reduced to those for the stereo-shift technique. The error of the position calculated by the least squares method was the smallest among all the formulas for the shift-film technique in simulation.

Radioimmunodetection of lung cancer with IMACIS-1, I-131 labeled monoclonal antibodies to CEA and CA19-9. Comparison of accumulations in irradiated and non-irradiated site.

IMACIS-1 is a radiopharmaceutical containing a mixture of Iodine-131 labeled monoclonal antibodies to CEA and CA19-9. IMACIS-1 immunoscintigraphy was evaluated for tumor detection in 7 primary lung cancer and 2 metastatic lung cancer patients who received radiotherapy. No adverse side effects due to IMACIS-1 were observed in this study. Positive detection was achieved in 5 of 9 patients (55.6%). It was less, but nearly the same as the detection rate obtained with Gallium-67 citrate (67Ga-citrate) in these patients. There was no clear correlation between IMACIS-1 accumulation and the CEA or CA19-9 serum levels. The IMACIS-1 positive detection rate decreased in many of the irradiated lesions. We considered that the decreased number of tumor cells and changes in blood perfusion are some of the factors controlling accumulation in tumors.

[Experimental studies on the combined effect of radiation and UFT: 2. fractionated treatments combining UFT and X ray radiation].

The combined effects of fractionated radiation and UFT, which is a mixture of tegafur (FT) and uracil, have been studied using C3H mouse mammary carcinoma. The tumor was implanted in the right hind legs of and irradiated with 300R daily for either 10 or 15 days. UFT (FT 15mg/kg + uracil 33.6mg/kg) was intra-gastrically administered 2 hr. before irradiation. Dose modifying factor (DMF) of UFT obtained from the tumor growth delay assay was 1.52 for 10 fractions (3,000R) and 1.27 for 15 fractions (4,500R). The continuous administrations of UFT for one month after combination treatment suppressed the tumor regrowth. It is suggested that UFT is a useful radiosensitizer for concurrent fractionated radiation and useful adjuvant agent after radiation therapy.

[Experimental study of tumor detection using 131I-labeled F (ab)2 fragments of monoclonal antibodies to CA 19-9 and CEA (IMACIS-1)].

To determine if IMACIS-1 might have the capability of specifically pinpointing an adenocarcinoma in the human lung, xenografts of adenocarcinomatous nude mice that were injected with IMACIS-1 have been evaluated by scintigraphy, and the IMACIS-1 biodistribution in the tissue measured after sacrifice. Results have revealed that scintigraphic images obtained twenty-four hours after the IMACIS-1 injection showed some activity in the area of the tumor. At seventy-two hours after the IMACIS-1 injection, tumoral radioactivity was only seen in mice with a large tumor. At ninety-two hours after injection, the animals were sacrificed and a biodistribution study was performed. The IMACIS-1 uptake was expressed in counts per minute per gram of tissue. The tissue-to-blood uptake ratio in mice with a large tumor was 8.4 in the viable part of the tumor, 27.2 in the necrotic part of the tumor, 3.0 in the liver, and 1.5 in the spleen, respectively. In contrast, the ratio in mice with a small tumor was 3.4 in the viable part and 18.3 in the necrotic part. Immunoperoxidase staining with either the anti CEA or the anti CA 19-9 antibody was strongly visible in the necrotic part of the tumor.

[Experimental studies on the combined effect of radiation and UFT 1. Radiosensitizing effect of UFT under single X-ray exposure].

The combined effects of X-ray and UFT, which is a mixture of tegafur (FT) and uracil, were studied using C3H mouse mammary carcinoma. Tumors were irradiated with a single dose of 1,000 R, 2,000 R one week after intramuscular transplantation. UFT (FT 15mg/kg+Uracil 33.6mg/kg) was intragastrically administered 2 hours before irradiation. In the group treated by combination of UFT and 1,000 R, the dose modifying factor (DMF) of UFT was 1.28 on the tumor growth delay and 1.64 on the survival time. A decrease in pulmonary metastases was found in the group treated by combination of UFT and radiation. It is suggested that UFT is a useful oral drug for combined treatment with radiation.

[Radiation therapy of intracranial germ cell tumors].

The results of radiation therapy in 31 patients with intracranial germ cell tumors have been analyzed. The five-year survival rates were 70.1% for germinomas and 38.1% for teratomas. Three patients with germinoma have since died of spinal seeding. The prophylactic irradiation of the spinal canal has been found effective in protecting spinal seeding, since no relapse of germinoma has been observed in cases that received entire neuraxis irradiation, whereas teratomas and marker (AFP, HCG) positive tumors did not respond favorably to radiation therapy, and the cause of death in these patients has been local failure. Long-term survivors over 3 years after radiation therapy have been determined as having a good quality of life.