High-dose radiation therapy for inoperable non-small cell lung cancer without mediastinal involvement (clinical stage N0, N1).

PURPOSE: To evaluate the usefulness of radiation therapy alternative to surgery for clinical N0-N1 non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: From 1976 through 1989, 116 patients with NSCLC without mediastinal involvement were treated with definitive radiation therapy alone at Gunma University Hospital. All patients were treated with once-daily standard fractionation using 10 MV X-rays. The total dose ranged from 60 Gy to 80 Gy. RESULTS: The actuarial 2- and 5-year survival rates of the entire group were 43% and 20%, respectively with a median survival time of 19 months. The survival of 76 patients with stage T2 tumors was significantly better than that of 28 patients with T3 tumors (mean survival time 21 versus 15.5 months; p < 0.05). Sixty-two patients with tumors less than 5 cm in diameter had a 2-year progression rate of 20%, in comparison with 39% of 54 patients with tumors greater than 5 cm. The difference of survivals for these 2 groups was statistically significant. Twelve patients given a total dose of 80 Gy or more had only 17% local progression at the time of last follow-up, however, 5 of them developed severe stenosis of proximal bronchus after 6 to 15 months. CONCLUSIONS: These results should provide support for definitive radiation therapy using 60 to 70 Gy to manage the patients with medically inoperable NSCLC without mediastinal involvement.

Enhanced cytotoxicity in combination of low dose-rate irradiation with hyperthermia in vitro.

We have pursued an in vitro investigation using a rodent cell line to characterize the interaction of simultaneous low dose-rate irradiation (LDRI) and hyperthermia and to determine the role of LDRI in the development of thermotolerance in a fractionated hyperthermia schedule. Yoshida sarcoma cells growing in vitro were used in this study. Cell survivals were estimated by the Courteney soft agar clonogenic assay. A treatment device for LDRI treatment, which held eight 137Cs sources and agar plus containing the cells, gave an irradiation dose of 51.8 cGy/h to the cells. In the experiment of simultaneous LDRI and hyperthermia, the LDRI cytotoxicities were enhanced by hyperthermia over a non-lethal temperature range. High synergistic effects were observed in a lower temperature range (40, 41 and 41.5 degrees C) in contrast to higher temperature (42, 43 and 44 degrees C). In the experiment of alternate LDRI and hyperthermia, thermotolerance induced by initial heating was well developed during the LDR exposure but less expressed in comparison with the cells which had no LDRI exposure. The treatment of LDRI for 8 h may have affected the thermotolerance development in our experimental condition.

Gallium-67 scintigraphy in evaluation of malignant lymphoma of the thyroid gland.

During the period from 1982 to 1994, a total of 45 67Ga scintigrams were performed in 12 patients with malignant lymphoma of the thyroid gland. Eight scintigrams were performed before treatment, 12 during the course of radiation therapy, and 25 after treatment. Scintigrams before treatment showed intense uptake in the thyroid masses irrespective of their size. Two of four scintigrams revealed no accumulation in the clinically remaining masses that were given a radiation dose of less than 20 Gy. No accumulation or thyroid masses were observed in cervical regions that received an irradiation dose of 20 Gy or more. Distant involvement in the upper half of the body could be detected by 67Ga scintigraphy in all cases, while there were two false negative lesions in the abdominal or pelvic cavity. Abdominopelvic lesions involving the gastrointestinal tract were observed in four cases, including two autopsied cases. 67Ga scintigraphy is useful for the evaluation of malignant lymphoma of the thyroid gland, but other examinations are recommended when 67Ga uptake is observed in the abdominal or pelvic cavity.

Prognostic factors for loco-regional control and outcome of re-irradiation for patients with poorly-differentiated squamous cell carcinoma of the nasopharynx.

Retrospective analysis was performed to evaluate the prognostic factors for loco-regional control and the results of re-irradiation for 28 patients with recurrent, poorly-differentiated squamous cell carcinoma (PDSCC) of the nasopharynx. Twenty-four of them received re-irradiation. Local, local plus regional and regional recurrences were observed in 19, five and four patients, respectively. Except for three patients, all had Stage IV disease at the initial diagnosis. The only parameters influencing loco-regional recurrence were T and N stage categories. The median latent period from initial treatment to recurrence was 18.5 (range, 2-100) months. There was no difference in latent period by first recurrence site, although recurrent tumors confined to the nasopharynx or those only regionally developed had a longer latent period. Only four patients developed secondary distant bone metastases with a median latency of three months from loco-regional relapse. The patients with local recurrent tumors confined to the nasopharynx, and those with regional recurrences only, could be salvaged by re-irradiation, with five-year survival rates of 44 and 100%, respectively. Five of 28 patients (18%) developed severe chronic radiation sequelae: cerebrospinal complications in four patients, bilateral neck fibrosis in one. We conclude that recurrent PDSCC of the nasopharynx can be controlled by re-irradiation with some success. Radiation therapy techniques must, however, be carefully planned in order to avoid the severe late post re-irradiation sequelae. For patients with advanced non-curable local recurrences, palliative care should be recommended instead of agressive re-irradiation.

Prognostic factors of poorly-differentiated squamous cell carcinoma of the nasopharynx.

Retrospective analysis was performed with intent to evaluate prognostic factors in radiation therapy for 72 patients with histologically confirmed poorly-differentiated squamous cell carcinoma of the nasopharynx. The 10-year overall actuarial and cause specific survival rates were 36 and 40%, respectively. The median survival time was 43 months. Sixteen patients survived for more than 10 years (maximum 297 months). The five- and 10-year cause specific survival rates for Stages I, II, III and IV disease were 100 and 100%, 80 and 27%, 83 and 83%, and 38 and 31%, respectively. Two patients with Stage II disease died of a re-recurrent tumor more than seven years after their initial treatment. There was a significant difference between the survival curve for Stage I or III disease and that for Stage IV disease (P < 0.05). The patients with a T1-3 tumor had a statistically better survival rate than those with a T4 tumor (T1:T4, P < 0.001, T2 or T3:T4, P < 0.05). The patients with N0 had statistically better survival rates than those with N3 (P < 0.01). Twenty-eight patients developed loco-regional recurrence. Twenty-one patients developed distant bone metastases, most of which occurred within a year of the initiation of radiation therapy. The survival for the patients with loco-regional recurrence was nearly the same as that for the patients without loco-regional recurrence. The 10-year survival rates for patients with and without distant bone metastases were 0 and 48%, respectively (P < 0.001). Multivariate analysis revealed that the parameters influencing cause specific survival were stage categories of T and N, and adjuvant chemotherapy, whereas those influencing loco-regional recurrence were only stage categories of T and N. The only parameter to influence distant bone metastases was sex. We concluded the most important cause of failure for the patients with poorly-differentiated squamous cell carcinoma of the nasopharynx to be distant bone metastases.

[Radiation therapy in brain metastases].

From 1980 to 1985, 126 patients with a brain metastases from various malignant tumors were treated by hypervoltage irradiation with conventional fractionation at the Department of Radiotherapy at the Cancer Institute Hospital. The patients without an extracranial metastases or without neurological symptoms had a longer survival than did the other patients. Radiotherapy of more than 30 Gy improved the neurological functions and reduced the risk of death from the brain metastases. For long-term local control of brain metastases, whole brain irradiation with boost therapy for localized lesions may be a better treatment than other radiation methods and the total radiation dose required may be more than 50 Gy.

[Histopathological changes in the brain after radiotherapy of brain metastasis].

This is the histopathological analysis of 18 post-irradiated brains with metastases of breast cancers. There was no evidence of radiation necrosis, except for one with demyelinization and one with degeneration of nerve cells. There was no radiation damage in re-irradiated group. Whole brain irradiation of about 40 Gy may be safe, but that of 60 Gy or more may be not so safe. It may be more useful for preventing of radiation damage to take split-course-method or shrinking-technique at doses of 40 Gy or more. The combination of chemotherapy and radiation therapy seems to aggravate the course of radiation damage.

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.