Michitaka Yamakawa

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.

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.

Analysis of recurrence of squamous cell carcinoma of the uterine cervix after definitive radiation therapy alone: patterns of recurrence, latent periods, and prognosis

PURPOSE A retrospective analysis was performed with emphasis on the patterns of recurrence, latent period, and prognosis in patients with cervical squamous cell carcinoma of the uterus treated with definitive radiation therapy alone. Late recurrence, which was observed more than 5 years after the initial radiation therapy, was finally focused on and discussed. MATERIALS AND METHODS Between 1976 and 1994, 256 patients with squamous cell carcinoma of the uterine cervix without hematogenous metastasis were treated with definitive radiation therapy alone. The patients were staged as follows according to the FIGO classification: 26 in Stage I, 56 in Stage II, 124 in Stage III, 28 in Stage IVa, and 22 in Stage IVb. All the patients were treated with external beam irradiation and low-dose-rate intracavitary brachytherapy. RESULTS A total of 74 patients had recurrence. The recurrence appeared in 67 cases (90.5%) within 5 years. Metastasis to para-aortic and/or supraclavicular nodes developed later than other types of recurrence. Among patients with lymphogenous metastasis, there were more 5-year survivors after recurrence than with other types of recurrence. Patients with early recurrence, within 2 years of the initial therapy, had a worse prognosis than those with recurrence more than 2 years after treatment. Seven patients (2.7%) in all developed late recurrence more than 5 years after the treatment. The first site of recurrence was an abdominal para-aortic or supraclavicular node in all patients, excluding one patient who developed intrapelvic lymph node metastasis. Six patients had pelvic node metastasis detected with lymphangiography at the initial treatment. Median survival after late recurrence was 16.0 months. Two of 7 patients survived more than 3 years after secondary radiation therapy, and the remainder died of recurrent disease. CONCLUSION Patients with para-aortic and/or supraclavicular node metastasis that developed late after the initial treatment are more likely to survive due to secondary radiation therapy. Careful follow-up is emphasized for long-term survivors.

Treatment of superficial esophageal cancer by external radiation therapy alone: results of a multi-institutional experience

PURPOSE To assess the effectiveness and toxicity of external radiation therapy for superficial esophageal cancer. METHODS AND MATERIALS During the period from March 1979 to November 1996, 78 patients with superficial esophageal cancer received radiation therapy without intracavitary irradiation at nine radiotherapy institutions in Japan. All patients had histologically-proven squamous cell carcinoma. Endoscopic ultrasonography was performed in 34 patients to discriminate mucosal from submucosal cancer. Most of the patients had received radiation therapy using conventional fractionation at an average dose of 65.5 Gy. RESULTS The survival rates at 1, 2, and 5 years were 88%, 73%, and 45%, respectively. The local control rates at 1, 2, and 5 years were 85%, 79%, and 66%, respectively. Although the difference was not significant, the survival rate of cancer patients with a tumor invading the submucosa was lower than that of the other patients. In 6 mucosal cancer patients, local recurrence was observed in 1 patient with extensive cancer. Regional lymph node recurrence and distant failure were not observed in mucosal cancer patients, while in 28 submucosal cancer patients, the 5-year survival rate and relapse free rate were only 49% and 43%, respectively. Univariate and multivariate analysis identified age as the only significant prognostic factor. Severe late injury, such as esophageal ulcer, perforation, and bleeding, was not observed. CONCLUSION External radiation therapy is effective for mucosal cancer. However, further investigation is needed to establish a better standard treatment protocol for submucosal cancer.

Clinical outcomes and prognostic factors for patients with early esophageal squamous cell carcinoma treated with definitive radiation therapy alone.

Goals and Background: There are great differences between treatment methods for early-stage esophageal cancer in institutions. Radiation therapy has been considered to be an effective modality as organ-preserving treatment of the disease. The aim of this study is to assess the effect and limitation of radiation therapy on patients with early esophageal cancer. Study: The subjects were 38 patients with stage I (T1N0M0) squamous cell carcinoma of the esophagus who had received definitive radiation therapy alone. Eleven tumors were assessed within the mucosal layer, whereas 27 tumors showed submucosal invasion by examination using endoscopic ultrasound. All patients were treated with more than 60 Gy using a conventional daily fractionation dose at 2 Gy. An additional boost with brachytherapy was performed for 20 patients, and the prescribed doses were 10 Gy (5 Gy × 2 times) with low dose rate (8 patients) and 9 Gy (3 Gy × 3 times) with high dose rate (12 patients). Outcomes and prognostic factors, including the efficacy of intraluminal brachytherapy, were investigated. Results: The cause-specific survival rate and the local control rate at 5 years were 82.6% and 86.3%, respectively. Recurrences were noted in 8 patients with submucosal cancer, but no recurrence was observed in patients with mucosal cancer. In the present study, tumor length was a statistically significant prognostic factor for cause-specific survival (P = 0.018) and tumor depth tended toward statistical significance (P = 0.073). In 27 patients with submucosal cancer, the tumor length was also statistically significant for the survival (P = 0.032). The 5-year cause-specific survival rates for the short tumor group and the long tumor group were 85.7% and 55.6%, respectively. On the other hand, the use of intraluminal brachytherapy had no significant effect on patient survival. Conclusion: Radiation therapy is very effective for early esophageal squamous cell carcinoma with tumor length less than 5 cm, but other treatment modalities, including chemoradiotherapy especially for inoperable patients, should be considered for submucosal cancer with a tumor length of 5 cm or more.

Radiation therapy for esophageal cancer in patients over 80 years old

PURPOSE A retrospective analysis was performed to investigate the treatment outcome and the significance of radiation therapy for esophageal cancer in patients over 80 years old. METHODS AND MATERIALS Between 1971 and 1990, 257 patients with squamous cell carcinoma of the esophagus were treated by radiation therapy. Of these, 40 patients over eighty years old were investigated. The reasons for radiation therapy were advanced age alone in 22 patients, Stage IV disease in 13, and medical problems in 5. Of these, 33 patients (83%) could be irradiated over 60 Gy. The cases with Stage I to III disease who received 60 Gy or more were defined as the curative radiation therapy group, and the others were defined as the palliative radiation therapy group. Actuarial survival rates were determined by the Kaplan-Meier method. RESULTS The 5-year disease-specific survival rate for the curative radiation therapy group (n = 25) was 34% with three intercurrent deaths. None of the patients in the palliative radiation therapy group (n = 15), including 13 cases with Stage IV and two given-up cases, survived over 2 years. No severe radiation damage was observed in either group. The 5-year disease-specific survival rate was 64% for complete response cases of local response, and 8% for partial response and no change cases (p < 0.01). The 5-year disease-specific survival rate was 64% for the patients with tumors less than 5 cm in length, and 8% for the patients with tumors over 5 cm in length (p < 0.001). No significant survival differences were found in regard to sex and tumor location. The patients with superficial spreading type and polypoid type tumors according to the radiologic findings had better prognoses than the patients with ulcerative type and circumferential type tumors. CONCLUSIONS Radiation therapy is a safe and effective treatment for esophageal cancer in patients over 80 years old.

Radiation therapy alone for stage I (UICC T1N0M0) squamous cell carcinoma of the esophagus: Indications for surgery or combined chemoradiotherapy

Background and Aim:  The aim of this study was to clarify the efficacy and limitations of radiation therapy (RT) for superficial esophageal carcinoma, and to explore the indications for more aggressive therapy, such as combined chemo‐radiotherapy.

Mucosa-associated lymphoid tissue lymphoma of the esophagus: a case report.

&NA; Carcinomas are the most common malignancies of the esophagus. Primary malignant lymphoma involving the esophagus is rare, with only a few cases of mucosa‐associated lymphoid tissue (MALT) lymphoma of the esophagus having been reported. We report the case of a 74‐year‐old man who was diagnosed with an esophageal MALT lymphoma. Generally, MALT lymphomas are indolent and tend to disseminate slowly; however, the behavior of this disease is not known clearly, and a standard treatment has not been established because of its rarity. Although complete response was confirmed with 36‐Gy irradiation, careful follow‐up is necessary for the patient.

EVALUATION OF EXTERNAL BEAM THERAPY AND THREE BRACHYTHERAPY FRACTIONS FOR CARCINOMA OF THE UTERINE CERVIX

PURPOSE A retrospective analysis was performed to evaluate external beam therapy and three brachytherapy fractions for patients with squamous cell carcinoma of the uterine cervix, compared with those with other histological types. METHODS AND MATERIALS Three hundred and twenty-two patients with carcinoma of the uterine cervix received external pelvic irradiation combined with three sessions of low dose rate intracavitary irradiation within 6 weeks. Two hundred and ninety-three patients had squamous cell carcinoma (SCC), whereas 29 patients had nonsquamous cell histology (N-SCC): 18 had adenocarcinoma, 5 had undifferentiated carcinoma, 4 had adenosquamous carcinoma, and 2 had adenoacanthoma. Survival rates, patterns of failure, local control rates, and complications in the patients with SCC were compared with those in the patients with N-SCC. RESULTS The 5-year overall actuarial survival rates for the patients with SCC and for those with N-SCC were: 84% and 100% in Stage I disease, 72% and 38% in Stage II disease, 52% and 17% in Stage III disease, and 29% and 0% in Stage IV disease, respectively. The 5-year cause specific survival rates for the patients with SCC in Stages I to IV disease were 100%, 87%, 72%, and 39%. Corresponding rates for the patients with N-SCC were 100%, 43%, 25%, and 0%. There was a statistically significant difference between the survival curves for two histological types in Stage II B, III B, and IV A diseases. The local control for the patients with N-SCC was worse than in the patients with SCC. The crude moderate and severe rectal complication rates (Grades 3 and 4) for the patients with SCC and for the patients with N-SCC were 7.5% and 3.4%, respectively. Only one patient with SCC developed chronic small intestinal injury in this series. We observed four patients with SCC who developed Grade 2 and four with Grade 4 urinary bladder complications. CONCLUSIONS Three sessions of intracavitary brachytherapy were a safe and effective procedure for the patients with SCC and the outcome of radiation therapy in the patients with SCC was satisfactory even in advanced cases. However, local control of N-SCC is difficult to achieve by this method and the prognosis for patients with N-SCC was significantly worse than that for patients with SCC.

A case of pulmonary ossified adenocarcinoma with marked osteoplastic bone metastasis

We report the case of a 53-year-old man suffering from a pulmonary adenocarcinoma with ossification and diffuse metastatic osteoplastic lesions throughout the skeletal system. This is a rare condition in lung carcinomas. Radiographs of the chest and bones demonstrated mineral densities in the primary tumor and multiple expansive osseous lesions with a diffuse sclerotic pattern resembling multiple bone metastases from prostatic carcinoma.