Masaya Furuta

Limited field irradiation for medically inoperable patients with peripheral stage I non-small cell lung cancer

The outcome of limited field irradiation for medically inoperable patients with peripheral stage I non-small cell lung cancer (NSCLC) was analyzed to discuss the elective irradiation of regional lymph nodes. From 1976 through 1994, 36 patients with peripheral stage I NSCLC were treated with definitive radiation therapy (RT) alone at Gunma University hospital. The total dose ranged from 60 to 81 Gy with a 2 Gy-daily standard fractionation, although only one patient received 48 Gy. Ten patients received elective irradiation of the regional lymph nodes with a total dose of 40 Gy or more. The overall response rate was 97% with 31% complete responses. The overall survival rates at 3 and 5 years were 42 and 23%, and disease-specific survival rates were 56 and 39% at 3 and 5 years, respectively. In 26 patients without the elective regional irradiation, disease-specific survival rates at 3 and 5 years were 53 and 40%, respectively, whereas they were 64 and 39% in 10 patients with the regional nodal irradiation. The cumulative 5-year local progression rate was 28%, and the overall progression rate was 60% at 5 years. Four patients had a local recurrence as the only site of initial tumor progression. Combined local and regional progression was seen in two patients, and one patient had a local recurrence in combination with distant metastasis. Twelve patients had distant failure without evidence of local or regional progression. Only one patient without regional nodal irradiation developed an isolated regional failure. No patient had serious complications related to RT. High-dose limited field RT is justified for medically inoperable patients with peripheral stage I NSCLC. The regional nodal irradiation can be omitted in these pulmonary compromised patients because of the low regional relapse rate. Dose-escalation by a conformal RT with a small target volume can be expected to provide a better local control rate and better survival.

Outcome of radiation therapy for patients with Kasabach-Merritt syndrome

PURPOSE The efficacy of radiation therapy for Kasabach-Merritt syndrome, which is characterized by a huge hemangioma with consumption coagulopathy, remains controversial. In this study, we retrospectively investigated the treatment outcome of radiation therapy for seven neonates with Kasabach-Merritt syndrome. METHODS AND MATERIALS During the past 25 years we have seen seven children with Kasabach-Merritt syndrome who were treated with radiation therapy. Their ages ranged from 1 day to 5 months, with a median age of 1 month. The hemangioma was located in the extremities in four of seven children. Tumor sizes ranged from 70 cm to more than 150 cm in greatest diameter. Initial platelet counts were all less than 40,000/mm3 except for one patient. In principle, the total dose applied to the hemangioma was 8-10 Gy, with a daily dose of 1 Gy five times a week. RESULTS Four of seven hemangiomas responded dramatically, with a concomitant rise of the platelet count to radiation therapy. Although the remaining three hemangiomas, all of which were ill circumscribed by widespread overlying shiny, dusky purple skin, became less tense during radiation therapy. Disseminated intravascular coagulopathy was not improved, but they have responded favorably to two or three courses of radiation therapy with an extended radiation field by 1.5 years of age. As a result, all seven patients are now surviving with no evidence of hemangioma or hematological abnormalities. Shortening of the extremity was observed in three patients who received multiple courses of radiation therapy. CONCLUSIONS Radiation therapy appears to be one of the effective treatment options for Kasabach-Merritt syndrome despite the risk of growth delay and malignancy.

Rapid rise in FDG uptake in an irradiated human tumour xenograft

In order to investigate early changes in the glucose metabolism of irradiated tumours, tumour uptake of 2-[18F]fluoro-2-deoxy-d-glucose (18FDG) was studied in human tumour xenografts. Three human tumour lines [ependymoblastoma (NNE), small cell lung cancer (GLS), and glioblastoma (KYG)] showing different radiosensitivities and incidences of radiation-induced apoptosis were subcutaneously transplanted into nude mice, and were irradiated at a single dose of 10 Gy. Then 0.5 mCi of18FDG was intravenously administered 1 h before sacrifice. The animals were sacrificed at 2, 4 and 6 h following irradiation, and18FDG accumulation in the tumours was examined. Before irradiation, GLS and KYG tumours showed significantly higher rates of18FDG accumulation compared with NNE tumours (P <0.004 andP <0.001, respectively). NNE (the most radiosensitive tumour with the highest incidence of radiation-induced apoptosis), however, displayed a 2.3-fold higher rate of18FDG accumulation at 2 h following irradiation compared with a non-irradiated group (P <0.01), and thereafter showed a plateau up to 6 h. The accumulation did not increase significantly in the other tumours with lower radiosensitivity and much less radiation-induced apoptosis. The rapidity of the increase in18FDG accumulation in the most radiosensitive tumour line, occurring as early as 2 h following irradiation, suggests that the increase was independent of recovery phenomena following radiation damage.

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.

Definitive radiation therapy for medically inoperable patients with stage I and II non‐small cell lung cancer

The treatment results of 84 patients with clinical stage I and II non-small cell lung cancer (NSCLC) treated with definitive radiation therapy (RT) alone at Gunma University Hospital from 1976 through 1989 were retrospectively analyzed. All patients were treated with 10 MV X-rays using anteroposterior parallel opposed fields. The total dose ranged from 60 to 80 Gy, except for one patient given 90 Gy with once-daily standard fractionation. The 2-and 5-year survival rates were 74% and 31% for 28 patients with stage I disease, compared with 40% and 19% for 56 patients with stage II, respectively (P < 0.05). Fifty-three patients with tumors less than 5 cm in diameter had an in-field progression rate of 14% at 2 years, in comparison with 38% of 31 patients with tumors greater than 5 cm (P < 0.05). The difference of survival rates for these two groups was statistically significant (P < 0.005). Ten patients given a total dose of 80 Gy or over had only 17% local progression at the time of last follow-up, however, they had not been alive beyond 3 years because they developed pulmonary insufficiency due to severe stenosis of the proximal bronchus. A multivariate analysis indicated primary tumor size as the only significant prognostic factor for survival. In conclusion, the tumor size was the most important factor not only for local control but also for distant failure. It was also suggested that the optimal radiation dose for medically inoperable stage I-II NSCLC ranged from 60 to 70 Gy with once-daily standard fractionation. Radiat Oncol Invest 1996;4:165–170.

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.

Clinical implication of symptoms in patients with non-small cell lung cancer treated with definitive radiation therapy

To clarify clinical significance of symptoms presented at the beginning of treatment, we analyzed the symptoms in 240 patients with non-small cell lung cancer treated with definitive radiation therapy. Symptoms were classified into four groups: no symptom (Grade 0), cough, sputum/hemosputum and fever up (Grade 1), chest pain and breathlessness (Grade 2), appetite loss, body weight loss, SVC syndrome, hoarseness, and pain in the upper limb/shoulder (superior sulcus tumor) (Grade 3), and their therapeutic outcomes were examined. The 2- and 5-year overall actuarial survival rates for patients with squamous cell carcinoma were 38.5% and 15.4% for Grade 0, 40.5% and 20.1% for Grade 1, 17.9% and 2.6% for Grade 2, and 15.8% and 5.3% for Grade 3. A statistical difference was noted in survival between Grades 0-1 and Grades 2-3 (P < 0.01), but was not seen between Grades 0 and 1, or between Grades 2 and 3. As for patients with stage III disease alone, the difference in survival was still significant between Grades 0-1 and 2-3 (P < 0.05). In patients with adenocarcinoma/large cell carcinoma, however, no obvious relationship was found between symptoms and prognosis, except for body weight/appetite loss. In conclusion, though the symptoms closely related to clinical stage and performance status and not an independent prognostic factor, chest pain and breathlessness correlated with poor therapeutic outcome as well as body weight loss and T3-4 related symptoms, while cough, sputum (hemosputum), and fever were favorable symptoms in patients with squamous cell carcinoma who received definitive radiation therapy.

Radiation therapy for stage III non-small cell lung cancer invading chest wall.

The treatment outcome and prognostic factors for Stage III non-small cell lung cancer (NSCLC) invading the chest wall and treated with definitive radiation therapy alone were investigated. From 1976 to 1990, 40 consecutive patients with Stage III NSCLC invading the chest wall underwent radiation therapy alone. There were 31 with Stage IIIA and nine with Stage IIIB. Squamous cell carcinoma was present in 30 patients (75%). All the patients underwent radiation therapy at a total dose of 60-80 Gy at 2 Gy per fraction. Local pain completely disappeared in 11/13 (85%) and decreased in the remainder after treatment. The 5-year survival rate was 8% for all patients, 10% for Stage IIIA and 0% for IIIB (P = 0.02), 11% for lesions invading the parietal pleura and 0% for those invading the ribs or spine (P = 0.2). Good performance status, Stage IIIA, metastases of lymph nodes less than N3 and small tumor size were better prognostic factors by univariate analysis. By multivariate analysis, performance status (P = 0.01) and Stage (P = 0.03) were the important prognostic factors. Five-year local progression-free survival rates were 51% for patients with lesions invading the parietal pleura and 0% for those invading the ribs or spine (P = 0.009). Good pain relief was achieved in patients with lesions invading the ribs or spine by radiation therapy. Tumors invading the parietal pleura were fairly well controlled by radiation therapy alone.

Malignant neuroendocrine tumor presenting a huge mediastinal mass controlled with radiation therapy

A case of malignant neuroendocrine tumor presenting a huge mediastinal mass controlled with radiation therapy is reported. A thoracotomy was performed on a 57-year-old male and a mass was found to invade the trachea, main bronchus, and left atrium. The tumor was unresectable. Subsequently, cisplatin was administered, but the tumor grew in size and radiation therapy was recommended. The tumor responded well to thoracic irradiation (56 Gy) and disappeared. Three months later, lymph nodes metastases were noted in the retrocrural and upper abdominal paraaortic regions, but these were controlled again with palliative irradiation. Without further treatment, he survived free of disease for over 5 years. Specimens obtained during the thoracotomy showed that the tumor consisted mainly of small round cells with a rosette formation. Immunohistochemically the tumor was positive to NSE and slightly positive to keratin, but negative to LCA, L26, UCLH-1, EMA, Leu7, and chromogranin, suggesting a malignant tumor derived from neuroendocrine tissue.

The role of radiation therapy for stage IIIB non-small cell lung cancer: Impact of clinical nodal stage on survival

BackgroundFrom 1976 through 1989, 46 patients with stage IIIB non-small cell lung cancer (NSCLC) without malignant effusion were treated with definitive radiation therapy (RT) at Gunma University Hospital.MethodsAll patients were treated with 10 MV x-rays using antero posterior parallel opposed fields. The total dose ranged from 60 Gy to 70 Gy (mean dose; 66 Gy) with once daily standard fractionation.ResultsThe actuarial two and five-year survival rates of the entire group were 22% and 10% respectively with a median survival time (MST) of 10 months. The survival of 18 patients with stage NO-2 disease was significantly better than the 28 patients with stage N3 disease (MST 21 versus 9 months;P<0.05). There were no significant differences in survival based on age and sex. However, there was a borderline difference in survival rates between patients with a performance status of 0–1 and those with a status of 2–3 (P=0.06). Three patients with squamous cell carcinoma were alive after 5 years and were without disease progression. No patients with non-squamous cell carcinoma were free of disease after 5 years.ConclusionThese results provide support for the use of definitive RT to manage those patients with limited stage IIIB squamous cell carcinoma not extending to N3 stage.