Susumu Katano

High-dose radiation therapy for elderly patients with inoperable or unresectable non-small cell lung cancer

PURPOSE To evaluate definitive radiation therapy delivering doses in excess of 60 Gy for elderly patients aged 75 years or over with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS The treatment results for 97 patients aged 75 years or older (mean age 78 years; elderly group) with inoperable or unresectable NSCLC were retrospectively analyzed and compared with those for 206 patients younger than 75 year old (mean age 64 years; younger group). The elderly patients were classified into two groups; 67 patients aged 75-79 years (the elderly A) and 30 patients aged 80 years or older (the elderly B). Most of all patients were treated with a total dose of 60 Gy or more in 2 Gy daily standard fractionation. RESULTS The overall 2 and 5 year survival rates were 32 and 13% for the elderly A group, and 28 and 4% for the elderly B group, respectively, compared with 36 and 12% for the younger group. There was not a statistically significant difference in survival rates among three groups. In stage I-II NSCLC patients there was also no significant difference in survival curves among the three groups. In patients with stage III disease, however, the survival curve of the elderly B was inferior to those of the younger group and the elderly A group, although the difference was not statistically significant. After the treatment the deterioration rate of the performance status was only 5% in the younger group and 8% in the elderly group. Only three younger and two elderly patients died of late pulmonary insufficiency associated with high-dose irradiation to the proximal bronchus. No other treatment-related event was observed except for mild acceptable acute complications in the elderly groups. CONCLUSIONS Definitive radiation therapy is recommended to the elderly aged 75 years or older with inoperable or unresectable NSCLC, especially early stage disease, as an acceptable choice of treatment.

Severe complications in advanced esophageal cancer treated with radiotherapy after intubation of esophageal stents: a questionnaire survey of the Japanese Society for Esophageal Diseases.

PURPOSE A questionnaire survey was performed to evaluate the complications and prognosis of esophageal cancer treated with esophageal intubation before or during radiotherapy. METHODS AND MATERIALS Clinical data were accumulated on a total of 47 patients treated at 17 institutions in Japan. Five patients had Stage II, 30 Stage III, and 11 Stage IV, and the stage was unknown in 1 patient. Covered expandable metallic stents were inserted in 30 patients, uncovered expandable metallic stents in 13, plastic or silicon prosthesis in 3, and an unknown type in 1 patient. Esophageal stenting was performed before the start of RT for 23 patients and during the course of RT for 24 patients. The reasons for the stenting were severe stricture in 32 patients (Group 1) and esophageal fistula in 15 patients (Group 2). RESULTS The most frequent toxicity was formation or worsening of esophageal fistulas in 13 patients (28%), followed by massive hematemesis or GI bleeding in 10 patients (21%). In total, 24 patients (51%), including 10 patients with possible treatment-related deaths (Grade 5), had nonhematologic toxicities of Grade 3-5. The interval from the start of RT to the nonhematologic toxicity ranged from 16 to 312 days (median 78). The incidence of toxicities was higher for Group 1 (59%) than for Group 2 (33%), although the difference was not statistically significant. The median survival time for those with Stage II-III and Stage IV was 5 and 3.5 months, respectively. CONCLUSIONS Patients with esophageal intubation before or during RT have a high risk of life-threatening complications, especially for those with severe esophageal stricture. Because long survival is expected for a substantial proportion of patients with locally advanced esophageal cancer after chemoradiotherapy, palliative intubation should be delayed until radiotherapy or chemoradiotherapy appears to have failed.

Radiation therapy for Stage I–III epidermoid carcinoma of the lung

From 1976 through 1985, 142 patients with Stage I–III epidermoid carcinoma of the lung received radiation therapy (RT) with total doses of 60–80 Gy at Gunma University Hospital. Patients with performance status (PS) 0–1 had an actuarial survival of 47% and 24% at 2 and 5 years, compared with 27% and 7% in those with PS 2, and 10% in PS 3 (p < 0.01). The actuarial survival rates for stage I, II, IIIA and IIIB were 75%, 44%, 32% and 19% at two years, and 31%, 22%, 13% and 10% at five years, repectively (p < 0.05). At five years, 26% of the patients with tumors less than 5 cm in diameter had survived, in contrast to 11% in those with tumors greater than 5 cm in diamter (p < 0.001). Patients given a total dose of 80 Gy or over had a lower long-term survival rate than those given a total dose of 60–79 Gy. Four patients irradiated over 80 Gy at the proximal portion of bronchi developed severe bronchial stenotic changes resulting in pulmonary insufficiency and died of intercurrent pulmonary disease without evidence of recurrence of the carcinoma at one or three years after RT. Patients with the primary tumors located in the upper lobes or the superior segment of the lower lobes had an excellent prognosis (p < 0.05). Stage N3 disease or malignant effusion revealed unfavorable prognostic factors. For age, sex and histologic subtypes, there were no significant differences in survival. For the five year survivors, the total irradiated doses were 60–70 Gy, and the size of the radiation field given over dose of 40 Gy was mostly 100 cm2 or less. In our results, the patients with epidermoid carcinoma of the lung without distant metastasis or malignant effusion were expected to be offered a realistic probability of long-term survival by RT alone.

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.

Stereotactic radiotherapy for locally recurrent nasopharyngeal carcinoma.

Objective: To determine the efficacy of stereotactic radiotherapy (SRT) in the treatment of recurrent nasopharyngeal carcinoma. Study Design: A retrospective review of the outcome of SRT for patients with recurrent nasopharyngeal carcinomas following definitive conventional radiation therapy. Methods: Five patients were treated with daily static multiportal irradiation. Two Gy was administered with eight isocentric portals in a single plane 5 days a week, and the plane was changed for every 20 to 30 Gy. Of these patients, three had poorly differentiated squamous cell carcinoma. Tumor sizes ranged from 1 to 15 cm 3 , with a median size 3.2 cm 3 . Median follow‐up time from SRT was 34 months (range, 4–61 mo). Results: Four of five recurrent tumors responded well and achieved complete regression. Three patients have survived without evidence of local recurrence with a median follow‐up time of 34 months. Marginal recurrence was observed at the posterosuperior wall in a patient with adenoid cystic carcinoma at 30 months after SRT. One patient who received SRT after the two complete courses of radiation therapy died 6 months after SRT as a result of rupture of a branch of the left carotid artery, but autopsy revealed no local residual tumor. Conclusions: Stereotactic radiotherapy with isocentric multiportals in one plane, which is changed at every 20 to 30 Gy, can provide local control with acceptable toxicity in patients with recurrent nasopharyngeal carcinoma, but increased clinical experience and longer follow‐up will be necessary to evaluate the overall role of this technique in nasopharyngeal carcinoma.

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.

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.

Salvage 125I Seed Implantation for Prostate Cancer with Postradiation Local Recurrence

Introduction: Although radiotherapy has been important in the therapy for localized prostate cancer, prostate-specific antigen failure may occur. This study evaluated the effects and side effects of 125I low-dose-rate brachytherapy for patients with postradiation local failure. Patients and Methods: 15 patients who received salvage brachytherapy were analyzed. A prescribed dose of 144 Gy was selected. Median follow-up calculated from the date of salvage brachytherapy was 33.0 months (range 6-51). Results: 5 patients (33.3%) developed prostate-specific antigen failure. The biochemical relapse-free survival rate was 100% at 1 year, 91.7% at 2 years, and 60.2% at 3 years. All acute genitourinary and gastrointestinal adverse events were in grade 1-2 according to Common Terminology Criteria for Adverse Events version 3. As for late adverse events, 1 patient (6.7%) developed grade 3 hematuria at 17 months postsalvage. Conclusions: Although careful patient selection is needed, salvage 125I prostate brachytherapy appears to provide good prostate cancer control with an acceptable rate of complications for patients with local recurrence of prostate cancer after initial radiotherapy.

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.