Preliminary results of proton-beam therapy for stage III non-small-cell lung cancer.

BACKGROUND: We conducted a preliminary retrospective evaluation of the efficacy and toxicity of proton-beam therapy (pbt) for stage iii non-small-cell lung cancer. METHODS: Between January 2009 and August 2013, 27 patients (26 men, 1 woman) with stage iii non-small-cell lung cancer underwent pbt. The relative biologic effectiveness value of the proton beam was defined as 1.1. The beam energy and spread-out Bragg peak were fine-tuned such that the 90% isodose volume of the prescribed dose encompassed the planning target volume. Of the 27 patients, 11 underwent neoadjuvant chemotherapy. Cumulative survival curves were calculated using the Kaplan-Meier method. Treatment toxicities were evaluated using version 4 of the Common Terminology Criteria for Adverse Events. RESULTS: Median age of the patients was 72 years (range: 57-91 years), and median follow-up was 15.4 months (range: 7.8-36.9 months). Clinical stage was iiia in 14 patients (52%) and iiib in 13 (48%). The median dose of pbt was 77 GyE (range: 66-86.4 GyE). The overall survival rate in the cohort was 92.3% at 1 year and 51.1% at 2 years. Locoregional failure occurred in 7 patients, and distant metastasis, in 10. In 2 patients, initial failure was both locoregional and distant. The 1-year and 2-year rates of local control were 68.1% and 36.4% respectively. The 1-year and 2-year rates of progression-free survival were 39.9% and 21.4% respectively. Two patients experienced grade 3 pneumonitis. CONCLUSIONS: For patients with stage iii non-small-cell lung cancer, pbt can be an effective and safe treatment option.

Uniformity of biological effect in high-dose rate stepping source brachytherapy: an in vitro study.

In brachytherapy with a high dose rate of iridium-192, to make a flat isodose surface that covers a target volume, the dwell times of the single stepping source are computer adjusted. However, the dose rates of the irradiation vary with the positions in the volume. To examine this effect, we developed an in vitro model of stepping source brachytherapy with a 20 cm long target volume, and determined the uniformity of the biological effect in the volume on two human cancer cell lines (WiDr and A549) plated on a multi-well plate. When the source-cell distance was 10 mm, D1 (radiation dose for 1% survival) was similar in seven positions among the target volume for both cell lines. In contrast, at the 3 mm source-cell distance for one of the two cell lines (A549), D1 in the centre of the volume was significantly higher than at the periphery, suggesting a milder antitumour effect in the centre. Considering the possible decreased effect in the centre of the target volume, where most cancers clinically exhibit their maximum tumour volume, a minimum increase in radiation dose in the centre may be clinically reasonable, especially when dose reference points are set close to the source.

Radiation therapy for advanced gastric cancer.

A retrospective study of 75 patients with advanced inoperable gastric cancers, referred to the National Cancer Center Hospital between 1962 and 1982, was performed. According to the Borrmann classification based on X ray findings, Type 1 was found in 3 patients, Type 2 in 5, Type 3 in 40, and Type 4 in 15. Twelve patients could not be classified. The histological type was papillary adenocarcinoma in 7 patients, tubular adenocarcinoma in 23, mucinous carcinoma in 6, poorly differentiated adenocarcinoma in 14, signet ring cell carcinoma in 12 and others in 13. The site of remote metastasis in 19 patients was Virchow's lymph node in 8 patients, Douglas pouch in 3, liver and lung in 2 each and others in 4. All patients were treated by a either telecobalt 60 unit or a linear accelerator using 6 Mv photon and the total dose to primary lesion was 4000 cGy in 5 weeks to 7000 cGy in 8-9 weeks. Complete response (CR) was achieved in 6 patients or 8.0%, partial response (PR) in 46 or 61.3%, and no change (NC) in 23 or 30.7%. The response rate based on the sum of CR and PR was about 70%. The 50% survival period in months was 26.5, 7.3, and 3.2, respectively for patients with CR, PR, and NC. For the response of advanced gastric cancer to chemotherapy in the National Cancer Center Hospital, the combined use of UFT and Mitomycin C gave the highest rate, 46%. As for as local response is concerned, the response rate to radiation was 70%, a better result than that of chemotherapy alone.

Hyperthermic therapy of deep seated tumors: comparison of the heating efficiencies of an annular array applicator and a capacitively coupled radiofrequency system.

Among 82 cases of deep seated tumors treated by hyperthermia with an annular array applicator (AA) and/or a capacitively coupled 8 mHz system (CCS) combined with radiation therapy, 13 cases were treated by both devices. The efficiencies of tumor heating were compared in terms of the time required to attain 42 degrees C, the duration of heating time and the thermal dose as determined by a biological iso-effect formula for equivalent minutes at 42.5 degrees C. Temperature profiles and percent of temperature levels greater than 42 degrees C were better in the cases treated by the AA, but higher thermal doses were obtained with the CCS because longer treatment times were tolerated with the CCS than with the AA. Methods are necessary to prevent excess elevation of body temperature in the case of the AA, and to reduce superficial pain where the applicators contact the skin in the case of the CCS.

Dose equivalence for high-dose-rate to low-dose-rate intracavitary irradiation in the treatment of cancer of the uterine cervix.

By comparing the incidence of major radiation injury, we estimated doses clinically equivalent for high-dose-rate (HDR) to conventional low-dose-rate (LDR) intracavitary irradiation in patients with Stages IIb and IIIb cancer of the uterine cervix. We reviewed a total of 300 patients who were treated with external beam therapy to the pelvis (50 Gy in 5 weeks) followed either by low-dose-rate (253 patients) or high-dose-rate (47 patients) intracavitary treatment. The high-dose-rate intracavitary treatment was given 5 Gy per session to point A, 4 fractions in 2 weeks, with a total dose of 20 Gy. The low-dose-rate treatment was given with one or two application(s) delivering 11-52 Gy to the point A. The local control rates were similar in both groups. The incidence of major radiation injury requiring surgical intervention were 5.1% (13/253) and 4.3% (2/47) for low-dose-rate and high-dose-rate groups, respectively. The 4.3% incidence corresponded to 29.8 Gy with low-dose-rate irradiation, thus, it was concluded that the clinically equivalent dose for high-dose-rate irradiation was approximately 2/3 (20/29.8) of the dose used in low-dose-rate therapy.

High-dose-rate intracavitary irradiation in the treatment of carcinoma of the uterine cervix: early experience with 84 patients.

Eighty-four patients with previously untreated invasive carcinoma of the uterine cervix were treated by high-dose-rate intracavitary irradiation using a remotely controlled afterloading system (Ralstron) with or without external irradiation at the National Cancer Center Hospital, Tokyo, between 1977 and 1981. Survival rates and local control rates were comparable to those for 372 patients treated by low-dose-rate intracavitary irradiation with or without external irradiation from 1972 to 1981 at the hospital. The incidence of major complications was 5.1 and 2.4% for the patients treated by low-dose-rate intracavitary irradiation and by high-dose-rate irradiation, respectively. The results are comparable to those reported by other institutions. We have abandoned the conventional low-dose-rate intracavitary irradiation with the impression that the high-dose-rate remotely controlled afterloading system is a good alternative to the conventional one.

Carcinoma of the uterine cervix treated with external irradiation alone.

One hundred and four out of 2701 patients with carcinoma of the uterine cervix were treated with a curative intent by external irradiation alone at the National Cancer Center Hospital from 1962 to 1979. All patients were judged inappropriate for the combined treatment of intracavitary and external irradiation, which was the treatment of choice for patients with advanced carcinoma of the uterine cervix in the hospital. The 5-year survival rate was 17% overall and 36, 17, and 5% for patients with Stage II, III, and IV disease, respectively. The local control rate was 20%, at 2 years, for all patients. Major complications were observed in five patients. There were no major complications in patients given a total dose of less than 115 in the Time Dose Fractionation factor (TDF). External irradiation combined with interstitial irradiation and/or hyperthermia is being considered to improve the results.

Radiotherapy of T1 glottic cancer with 6 MeV X rays.

We treated 154 patients with T1 glottic carcinoma with 6 MeV X rays through 16 cm2 parallel-opposing open fields on a free set-up delivering a median dose of 67 Gy in 6 2/3 weeks. Observed and relative 5-year survival rates for all patients were 87% and 100%, respectively. The local control rate at 5 years was 89%. Of 18 patients who clinically had local recurrence, 17 were salvaged by a secondary treatment. There were no complications requiring medical or surgical attention. A tendency toward increasing local control rates with increasing total doses was observed in the range between 57.5 Gy and 72.5. No significant correlation was found between local control rates and field size, daily dose, or the technique used. A tendency toward a lower local control rate was noted for patients whose anterior commissures were grossly involved; however, it is not known if this could be attributed to the use of 6 MeV X rays. The results are comparable to those obtained with 60Co as reported in the literature. It is concluded that 6 MeV X rays on a free set-up delivering 65-70 Gy in 6 1/2-7 weeks can be used satisfactorily for the treatment of early glottic carcinoma.

Linac-based small-field radiotherapy for brain tumors.

Small-field radiotherapy based on a 6-MeV linac and a conventional head mold is investigated as an alternative to radiosurgery with stereotactic frames. The system requires no additional device and allows fractionated treatment. The dose distributions obtained are comparable to those reported with a Gamma Unit. Overall positioning errors are within 2 mm. Using this approach, seven patients with brain tumors who could not have been treated otherwise, underwent fractionated radiotherapy with total accumulated doses ranging from 70 to 108 Gy. The treatment was tolerated well with no acute toxicity or adverse effect encountered during the follow-up period of 8-14 months. All of the patients remained free from disease progression in the treated volumes. Although the follow-up is brief, the preliminary results suggest that this is a simple and inexpensive but effective system for the treatment of small intracranial malignancies.

Stage I-II carcinoma of the anterior two-thirds of the tongue treated with different modalities: a retrospective analysis of 244 patients.

Treatment results of 244 patients with stage I-II cancer of the mobile tongue were analyzed according to the modalities employed (implantation, surgery, cryosurgery and intraoral irradiation). Overall local control rates at three years were 90 +/- 3% for implant, 89 +/- 7% for cryosurgery, and 84 +/- 9% for surgery. Local control rates in stage II patients treated with intraoral electron irradiation, however, were only 50 +/- 13%. Five-year survival rates were 72 +/- 3% with no significant differences observed in patients with either stage I or stage II regardless of treatment modality. Sixty percent (29/48) of the patients with local recurrences were salvaged by the second treatment. Since the local control and survival achieved by these modalities were similar, with the exception of patients with stage II treated by intraoral electron irradiation, we recommend interstitial implantation with iridium, intraoral electron irradiation or surgery for patients with T1 tumors, and iridium implantation or surgery for patients with T2 tumors. For those with superficial lesions measuring 5 mm or less in thickness, cryosurgery is being offered as an alternative. The patient can choose the treatment modality taking into account his/her age, sex and profession.

Radiation therapy for roentogenographically occult lung cancer by external beam irradiation and endobronchial high dose rate brachytherapy.

PURPOSE: We investigated the clinical usefulness of radiation therapy by external beam irradiation and endobronchial brachytherapy for the treatment of roentogenographically occult lung cancer. PATIENTS AND METHODS: From 1995 to 1996, five patients were treated with radiation therapy. We analyzed their treatment outcomes. The follow-up period varied from 3.0 to 3.8 years or until death. External beam radiation (40 Gy/20 fractions/4 weeks) was delivered to the tumor site alone, and not prophylactically given to the mediastinum. Endobronchial brachytherapy using high dose rate iridium (Ir)-192 was concurrently administered principally to a total dose of 18 Gy on the bronchial mucosa in three weekly fractions of 6 Gy each. RESULTS: Complete remission was obtained in all patients. Two patients died of intercurrent diseases at 12 and 21 months without any evidence of recurrence. The disease has been also controlled in the other three cases. With the above doses, three small tumors < 1 cm were controlled without adverse effect. In two tumors, the dose reference points were set 2-7 mm beneath the mucosa, and larger doses were administered by brachytherapy. An applicator acting as a spacer was not used in these cases. The tumors were controlled, although the irradiated bronchi showed severe stenosis in 6 months following the treatment. However, the patients were asymptomatic and did not need further intervention. CONCLUSION: External beam irradiation combined with endobronchial brachytherapy was useful for the treatment of roentogenographically occult lung cancer as an alternative to surgery. Further investigation is needed to determine the optimal doses of radiation therapy.

Endobronchial brachytherapy for recurrent thymoma showing endobronchial polypoid growth.

The authors report a case of recurrent thymoma displaying endobronchial polypoid growth. Initially, the patient had invasive thymoma with intracaval growth into the right atrium. He was treated with multimodality therapy consisting of chemotherapy, surgical resection, and radiotherapy (50.4 Gy). Both 3 years and 6 years after the initial treatment, the tumor recurred outside the reconstructed superior vena cava. The patient was treated with repeated radiotherapy (50.4 Gy and 40 Gy), and remission was achieved. Eight years after the first therapy, an endobronchial polypoid lesion was detected in the right upper lobe bronchus and was histologically found to be thymoma. Endobronchial high-dose rate brachytherapy (20 Gy at 3 mm/5 fractions) was carried out for palliation because the recurrent tumor occurred outside of the superior vena cava area, which had been reirradiated. After the treatment, the endobronchial tumor shrunk remarkably in size without adverse effects. No tumor regrowth has been noted after a follow-up of 10 months.

Hyperthermia for bone and soft tissue sarcoma: relationship between computerized tomographic and histological findings.

Between 1983 and 1992, 38 patients with 44 tumors of bone and soft tissue sarcoma were treated by hyperthermia combined with radiotherapy or chemotherapy. The overall response rate in this series was 48% (21/44). The average time for heating to 42 degrees C and the average maximum temperature did not correlate with the local effect. The percentage of the low density area on CT images and the average maximum temperature were well correlated. When 100% necrosis was evaluated as CR and up to 50% necrosis as PR, the local response rate was elevated from 42% to > 65%. Bone and soft tissue sarcomas are good targets for hyperthermia combined with radiotherapy and chemotherapy. Some tumors indicated for this study were too large to heat with the present heating apparatus. Percent low density and percent necrosis were correlated to some degree, but adoption of this phenomenon as a criterion for evaluation should be considered carefully.

Ir-192 brachytherapy by an afterloading technique: initial experience at the National Cancer Center Hospital, Tokyo.

Twenty-nine patients with various tumors treated by 192Ir brachytherapy at the National Cancer Center Hospital from 1977 to 1984 were reviewed. Of 10 patients with carcinoma of the extrahepatic bile duct, three with carcinoma of the urinary bladder, and three others with various tumors, none showed locally controlled disease. Two of six patients with recurrent brain tumor, three of five with skin tumor and two with carcinoma of the female genital tract showed locally controlled disease. Although the effectiveness of this mode of treatment needs to be more clearly demonstrated, it is easily applied to clinical practice and is at least as effective as radium 262 implantation.

Local effect of hyperthermia for superficial and shallow-seated tumors.

In approximately seven years, 134 patients with 161 tumors were treated by hyperthermia combined with radiation or chemotherapy at our department. The primary tumors were breast cancer, head and neck cancer, and soft tissue tumors in most patients. Adenocarcinoma was the most frequent, followed by squamous cell carcinoma and soft tissue sarcoma. The local response rates for primary inoperable advanced, metastatic, and local recurrence of breast cancer were 88% (7/8), 50% (10/15), and 86% (18/21), respectively. The local response rate of 39 tumors of neck lymph nodes was 49% (19/39). A total of 26 tumors of bone and soft tissue were treated. Five tumors showed CR and six PR, for a total response rate of 42%. Among 20 patients with malignant melanoma, CR and PR were 25% (5/20) and 30% (6/20), respectively. The local response rate for all patients with superficial and shallow-seated tumors was 58% (94/161). In some tumors classified as showing NR, complete disappearance of tumor cells was demonstrated by a post-treatment histological examination. The efficacy of hyperthermia, when evaluated solely on the basis of tumor size, is likely to be underestimated.

Suppression of bony growth of the orbit after radiotherapy for retinoblastoma.

Suppression of the growth of orbit and skull in 13 retinoblastoma patients treated by radiotherapy was investigated. The age of patients at the time of treatment ranged from 1 month to 6 years and 11 months. They were examined after three to 18 years. Suppression of the growth in involved areas and other parts of the skull within the beam of radiation were estimated by inspection, X-ray findings, and X-CT examinations. The involved orbit received more than 32 Gy, and the suppression of bone growth was prominent. At the opposite temporal bone, suppression of growth was prominent in eight cases out of 11, in these cases, the radiation dose was at least 14 Gy. Two cases, in whom the radiation dose was less than 12.6 Gy, have not shown any suppression of bony growth. Results were also obtained for a nominal single dose (ret). In all cases of more than 1,000 ret, suppression was prominent, but at less than 1,000 ret, four out of nine cases, and at less than 600 ret, two out of four cases showed suppression of bony growth. If the safety dose to avoid the suppression of bony growth is 400 ret, this is equivalent to three times the radiation dose of 200 cGy. In conclusion, the suppression of bony growth of the orbit and temporal area of the skull of young patients is caused by very small doses of radiation.

A comparison of swine abdominal temperature distribution after heating with BSD-1000, an annular phased array system (APAS), and Thermotron RF-8.

External hyperthermia for deep-seated tumors is still a difficult problem. We compared the abdominal temperature distribution in a pig after heating with BSD-1000, an annular phased array system (APAS), and Thermotron RF-8. Thirty elastic tubes were inserted into the upper abdomen of the pig and a thermocouple was inserted into each of the tubes. After heating, these thermocouples were moved at 1-cm intervals and the three-dimensional temperature distribution was obtained. The temperature distribution after heating with APAS and Thermotron RF-8 was compared by using the distribution on the longitudinal center line of each sagittal plane at 1-cm intervals from the center. The temperature was much higher and its distribution more homogeneous with APAS than Thermotron RF-8.

Treatment of metastatic gastric cancer by combined radiation and hyperthermia (report of two cases).

Two patients with metastatic carcinoma of the stomach on the abdominal wall were treated by radiotherapy using cobalt-60 gamma-ray or megavoltage electrons combined with hyperthermia induced with a Thermotron (8 MHz). The total dosage was 44 Gy fractionated into 11 doses (twice a week), by cobalt-60 gamma-ray and 10 hyperthermia treatments for patient 1, and 32 Gy fractionated into eight doses (twice a week) given by megavoltage electrons and five hyperthermia treatments for patient 2. In patient 1, the shrinkage of the tumor was more than 50%. No tumor cells were observed histologically at the end of treatment. In patient 2, the tumors completely disappeared. These results encourage us in the use of radiotherapy combined with hyperthermia for rather radioresistant adenocarcinoma.

Classification of the 16,471 patients treated by radiation therapy from 1962 to 1986, and crude five-year survival rates of patients in each category of radiotherapy treatment from 1962 to 1978 in the National Cancer Center Hospital.

The summation and classification of patients registered for planned radiation therapy in the 24-year period from 1962 to 1986, in the Department of Radiation Therapy, National Cancer Center Hospital, are reported. Patients numbered 16,471, and total sessions of treatment were 26,175. The ratio of the two figures, 1.58, is the average number of treatment sessions per patient. Peak age was 61-65 years' old and 56-60 years old, respectively for males and females. The most frequent primary site of disease for radiation therapy was the head and neck, followed by trachea, bronchus and lung, crevix uteri, breast, and esophagus. Frequency of squamous cell carcinoma was 38.0%; that of adenocarcinoma was 20.9%. Radical treatment was performed in 32.0% of patients in the first session, but this figure decreased to 24.7% for all sessions. There were many cases of secondary and primary palliative treatment, i.e., 31.8%. Radiotherapy was done in 70% of patients by megavoltage X-ray, with 9.4% treated by electron beam. Crude 5-year survival rates for each classification of malignant disease respective to the category of treatment policy from 1962 to 1978 were obtained. Among the radical treatment group, head and neck tumors, skin cancer, and Hodgkin's disease showed 5-year survival rates greater than 50%.

[Hyperthermia in bone and soft tissue tumors].

Local response of hyperthermia for soft tissue and bone tumors was investigated. Ten tumors were superficial tumors and 16 were deep seated tumors; 9 tumors were malignant fibrous histiocytoma, 5 were liposarcoma, 4 were neurogenic and 3 were myogenic sarcoma. The other five tumors were an angiosarcoma, a malignant mesenchymoma, an Ewing's sarcoma, a chordoma and an osteosarcoma. Some 23 tumors were heated in combination with radiation therapy, and 3 were combined with arterial infusion of ADR. Four of 10 superficial tumors disappeared (CR), and, 2 of 10 signified PR. Only one of 16 deep seated tumors showed CR, 3 were PR and 12 showed no response. But 4 of 12 tumors without regression in tumor volume indicated coagulation necrosis owing to histological examinations, and 5 of 12 were regarded as the same response from hypodensity area with CT examination after hyperthermia. Local response rate of of superficial tumors was 60% and that of deep-seated tumors was 81.4%.