Proton beam therapy has high potential for substantial improvements in the efficacy of radiation therapy due to the physical characteristics of the beams. Namely, the range of the protons is finite and is dependent on the particle energy. This permits the design of beams which penetrate just sufficient to irradiate the target tissues but to give no dose to the deeper non-target tissues. As a consequence, there can be important reductions of treatment volumes for some anatomic sites. The benefit from the smaller treatment volumes is that patient tolerance is increased and accordingly, dose to the target is raised with a resultant higher tumor control probability. As lesser volumes of normal tissues will be irradiated, the frequency and severity of radiation injury will be cut. An important truism is that radiation damage never appears in unirradiated tissues.
Clinical applications of proton beam therapy have yielded clinical gains in situations where smaller treatment volumes and higher doses to the targets have been realized. These are discussed. Results of proton therapy for 2800 patients with uveal melanoma treated by 70 CGE/5 fractions or 60 CGE/4 fractions from 3 centers show local control within the globe and survival rates to be 96% and 80% respectively. The local control rate for the high dose area was>99%. For chondrosarcoma and chordoma of the skull base and cervical spine, the 5 year actuarial local control rates were 76% and 67% respectively [176 and 39 patients respectively] in the series at the MGH/HCL. Quite promising results are being obtained for smaller groups of cancer patients with tumors at other sites. Also, the experience in the treatment of patients with AVMs by proton/helium ion beams are good and competitive with those from “Gamma Knife” and “Stereotactic Linear Accelerators”.
The design of clinical evaluations of proton radiation therapy is discussed. The two main points of attention in such studies are: 1] selection of the appropriate tumor targets; and 2] definition of the control treatment. For the latter, the highest feasible technology photon arm is considered a must. The challenge is not merely to achieve results superior to the medical standard of today but rather that of the end of the decade when the photon therapy in major centers will be based upon systems featuring 3 D planning, optimization software, on-line portal imaging, multileaf collimation etc. The choice of target tumors is recommended to concentrate on those with tumor control probabilities in the range of 0.2-0.6 for the high tech photon therapy, viz on the steep portion of the dose response curve for local control. This is so in order that the numbers of patient required to demonstrate the gain from an increment in dose of ≈10-15% be reasonably easy to obtain.

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To estimate the merits of conformation therapy we made a treatment planning comparison and analyzed the quantitative dose advantage of conformation therapy over conventional treatment using a dose-volume histogram (DVH) of the critical organs. The DVHs of the critical organs were calculated and compared using the same average target dose. By using the Histogram Reduction Method, the equivalent dose to the full organ (ED) and the complication probability of the critical organs were both calculated. Assuming that the complication probabilities of each organ were independent, the entire complication probability was calculated by multiplying the uncomplicated probabilities of each organ and subtracting the product from 1. Dose response curves were then drawn and the TD₅₀'s and/ or TD₁₀'s of both techniques were determined and compared. The selected tumor sites were the brain, lung, bile duct, periaortic lymphnodes, cervix, prostate, and rectum. In every site, conformation therapy was advantageous over conventional treatment by 4 Gy to 41 Gy (6% to 82%) of the administered dose. The difference was much greater than that of the integral dose. Conformation therapy was especially promising in abdominal and pelvic tumors, but not in chest tumors because of the radiosensitivity of the lung. From this study we concluded that conformation therapy, theoretically at least, is promising. However, this advantage will have to be tested clinically in the future with dose escalation studies.

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An attempt was made to form a theoretical radiation done-equivalent heat distributions to compare with a sample of calculated temperature distribution of hyperthermia by a radio-frequency (RF) generator, mediated by biological effects. Physical dose distributions for 10 MV X-rays were calculated by computer for treatment planning.F our-portals were used to focus the radiation on the tumor. A CT view of an ovarian tumor was used as a model. The radiation dose distribution was converted to radiation dose equivalent heat-treatment time distribution at 43°C. The obtained heat-treatment time at 43°C was further converted to temperature with a fixed treatment time of 60 minutes by a thermal dose equation. From these conversions, temperature distributions were constructed for the dose-distribution of four-portal irradiation. A feasible temperature distribution pattern was obtained by computing RF capacitive heating for the same CT view. This was compared with the temperature distribution derived from four-portal irradiation. The feasible temperature-distribution pattern for RF heating indicated a similar but better distribution in the tumor center and in the surrounding normal tissue, except at the tumor edge. Th ese results indicate need of biological consideration for dose distribution of different modalities. Additional relevant studies of thermal sensitivity of human cells, and normal andt umor tissue are encouraged to determine sensitivity and obtain possible predictive thermal doses for which the biological effects should be taken into account.

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Cell nuclear DNA ploidy patterns were determined by flow cytometricanalysis in 19 patients with esophageal carcinoma. Aneuploid DNA patterns were observed in 13 patients. Seventeen of the patients were treated by external radiotherapy of 50 Gy or more. Intraluminal brachytherapy was also performed in 15 of these patients and their local response to radiation was estimated by barium esophagograpy one month after completion of the radiotherapy. We investigated relations among the DNA ploidy patterns, clinical chara cteristics, and local radiation response. Four patients with lymph node metastasis were judged to have aneuploid DNA patterns. These patients with aneuploid pattern showed a favorable local response to treatment one month after radiotherapy. It is possible that the ploidy pattern of esophageal carcinoma could be a valuable predictor of the early local response to radiotherapy.

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We evaluated the clinical significance of postoperative radiation therapy following inadvertent simple hysterectomy for carcinoma of the uterine cervix. From September of 1975 through July of 1985, 21 patients with squamous cell carcinoma of the uterine cervix received radiation therapy after simple total hysterectomy. The figures of FIGO staging were Ib “occ” in 16 patients, stage Ib in 4 and stage IIb in 1. Eight patients were treated with external beam therapy (40-50 Gy/16-25 fractions/4-6 weeks) alone and 13 patients were treated with a combination of external beam therapy and high dose-rate intracavitary irradiation (20-30 Gy/4-6 f/2-3 w). Both the 5-and 10-year disease free survival rates were 89.8%. Seven patients (33.3%) developed complications, but these complications were transient and needed no medication. Our favorable result indicates that postoperative radiation therapy offers an opportunity for the cure of early cases of cervical carcinoma, such as stage Ib “occ”, which received an inadvertent simple total hysterectomy.

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Of 125 patients with primary malignant bone tumor referred to us for radiotherapy from 1959 to 1989, 4 had previously untreated giant cell tumors of bone. To evaluate the usefullness of radiotherapy in giant cell tumors of bone, we investigated histology, type of surgery, radiation dosage, pain relief, reossification, and clinical course in these patients. Patients were all female, with ages ranging from 16 to 21 years (mean, 19 years). In 3 patients, the primary tumor sites were weight-bearing bone. Histopathologically, the tumors were grade I in 2 patients, and II or III in each of the other patients. Two patients were treated with radiation alone, and the others were irradiated pre-or post-operatively. Radiation doses ranged from 40 to 69 Gy. Pain relief was achieved in 3 patients, and subjective relief was obtained with a dose of less than 20 Gy. Reossification of affected bonewas recognized 3 to 5 months after completion of radiotherapy. Local control was obtained in 3 patients, although there was no significant relation between local control and tumor size. Follow-up periods ranged from 2 years and 2 months to 17 years, and all patients are still alive. Three show no evidence of disease, and 2 who had been diagnosed with histological grade I giant cell tumor have survived for long periods (17 and 15 years). At present, all local lesions are well controlled, and we have encountered no malignant transformation that might be attributable to radiation therapy. We conclude that radiation therapy is the treatment of first choice for inoperable giant cell tumor with primary lesion in the weightbearing bones, and that it is a curative alternative which preserves motor function.

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The effect of radiation therapy on bone metastasis was studied by MR imaging. The present series included Groups I and II, Group I consisted of 32 patients with bone metastasis from lung cancer, breast cancer, renal cell carcinoma and various other malignancies that were evaluated by MR imaging before and after radiation therapy, Group II included 3 patients with preexising bone metastasis of breast cancer who were free from recurrence for more than five years after the radiation therapy. The signal intensities were standardized in 5 degrees;(I) iso-intense to normal bone marrow within the radiation field, (L) iso-intense to the muscles, (LL) hypointense to the muscles, (H) iso-intense to subctaneous fat, (HH) hyperintense to the fat.
Before radiation therapy, most bone metastasis was (L) on T1-weighted images, or (H) on T2-weighted images with enhancement by Gd-DTPA. Changes of MR images of Group I within or after 2 years had 5 variations in T1-/T2-weighted images; LL/HH (31%) as Type I, I/I (13%) as Type II, LL/LL (9%) as Type III, mixed changes as Type IV, and unchanged as NC. Gd-DTPA enhanced images before radiotherapy were mostly solid pattern in 23 of 27 patients. After radiation, the enhancement showed some decrease in 18 of these 23 patients with the following 3 patterns; mottled in 7, ring-shaped in 4 and lacking in 7. At this stage, we conclude that the decrease in enhancement was caused by radiation. Tumor size reduction on MR images was noted in 12 of 35 patients, also by radiotherapy. The 3 patients of Group II had Type III change (without enhancement).
These radiation-induced changes, in addition to past literature, reflect the pathologic features; Type I as liquefying tumor tissue, Type II as fatty change, and Type III as osteosclerosis or fibrosis. In this respect, the therapeutic effect of bone metastasis can be evaluated by the following parameters;(1) change of intensity on T1-and T2-weighted images, (2) Gd-DTPA enhancement and (3) size of tumor. Of 27 patients who showed good response to radiotherapy, 20 (74.1%) were estimated to be in the earlier stage; 5 were already in therapy and the other 15 were within 2 months after the completion of radiation therapy.
Bone metastasis has been diagnosed by X-ray films, radionuclide study and CT in the pre-MR era, however, MR imaging can be a promising diagnostic tool and a means of following up the effects of radiation therapy. Problems on precise pathologic-MR correlation should be solved in the future.

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High-dose-rate intraluminal irradiation with a ⁶⁰Co remote afterloading system, using our newly developed applicator, was performed in 15 cases of advanced biliary tract cancer (2 gallbladder cancers, 13 cholangiocarcinomas). The applicator which was thin with an outer diameter of 14 Fr had a double lumen which included of a small lumen for a guide wire for easy exchange to a drainage tube. Therefore, the irradiation procedure could be easily finished in a short time with in little distress to the patient. The tumor marker CA1 19-9 was useful in asessing the therapeutic effect and follow-up observation after treatment. The average tube-free period and survival time were 5.9 months and 8.3 months, respectively. Histopathological examination of the cases autopsied showed that the combination of intraluminal (30 Gy) and external (30 Gy) irradiation offered good local control of the cancer that was within 1cm from the source. Cholangiocarcinoma with relatively short length of obstruction, stage III or stage IV when the cancer infiltration was localized around the bile duct, achieved a comparatively long survival time. It was suggested that the combined use of high-dose-rate intraluminal radiotherapy, with precisely delivered radical radiation to tumors localized in the bile duct wall, and external radiotherapy delivered as additional radiation to the surrounding bile duct would provide radiotherapeutic advantage and contribute to survival after treatment for advanced biliary tract cancer.

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A megavoltage CT scanner using a 4 MV and a 6 MV radiotherapy beam has been developed. A detector system composed of 120 pairs of Cadmium. Tungustate scintillators and photo-diodes is attached to the treatment unit at the distance of 160 cm from the beam source. image reconstruction is performed at an engineering work-station with a standard filtered back projection algorithm. Scanning time and reconstruction time for a slice are approximately 35 seconds and 60 seconds, respectively. Although spatial resolution is as much as 4 mm the megavoltage CT has sufficient image quality to be applied for treatment planning and verification. Doses delivered to a patient with 4 MV and 6 MV are about 1.4 cGy and 2.8 cGy, respectively. These doses within or close to radiation fields are thought to be acceptable in the patients receiving radiation therapy. The megavoltage CT provides an accurate and quantitative means for detecting patient set-up errors. In addition when it is used for radiation therapy treatment planning, the positioning errors will be highly reduced since the deviations caused by transferring the patient from a CT couch to a treatment couch are minimized. CT numbers of this megavoltage CT can be directly used to calculate electron density for dose distribution calculation.

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