Norihiko Kamikonya

Radiotherapy of esophageal carcinoma: Role of high-dose-rate intracavitary irradiation

A total of 119 patients with squamous cell carcinoma of the esophagus who were seen during a 10-year period were analyzed retrospectively in terms of survival rate and local control rate in relation to treatment method and disease stage. All patients were treated with radiotherapy alone: 43 patients were treated with external irradiation plus high-dose-rate intracavitary irradiation (Group 1), 46 with external irradiation only, to 50 Gy or more (Group 2), and 30 with external irradiation to less than 50 Gy (Group 3). All patients of Group 3 died within 8 months (mean 3.5 months) after the initiation of radiotherapy. In Group 1, the 2-year survival rate was 27.9% for the patients in all disease stages and 44.0% for those in Stage 1 and Stage 2 in contrast to Group 2, with a 2-year survival rate of 4.3% for the patients in all stages and 9.1% for those in Stage 1 and 2. The local control rate was 62.8% in Group 1, significantly higher than 19.6% in Group 2. It is concluded that high-dose-rate intracavitary irradiation following external irradiation is an effective treatment modality for esophageal carcinoma, especially in a limited stage.

High-dose-rate intraluminal brachytherapy for esophageal cancer: 10 years experience in Hyogo College of Medicine☆

From May 1980 through December 1989, 148 patients with thoracic esophageal cancer were treated with high-dose-rate intraluminal brachytherapy (HDRIBT) following external radiotherapy (ERT). The standard treatment protocol was 60 Gy/6 weeks of ERT and 12 Gy/1 week of HDRIBT. The patients were divided into two groups according to disease stage. Sixty-six patients had limited disease (LD), and 82 patients had extensive disease (ED). The 2-year survival rate was 37% in LD group, and 7% in ED group. The 5-year survival rate of LD group was 18%. The 1- and 2-year actuarial local control rate was 66% and 64% in LD group, and 49% and 45% in ED group, respectively. In the total patients, ulceration, stricture, and fistula were found in 42 (28%), 15 (10%) and 6 (4%) patients, respectively; however, major complication defined as one resulting in a second hospitalization or requiring surgical intervention was 3 of the 42 patients with ulceration, 1 of the 15 patients with stricture, and all of the six patients with fistula. As to cause of death, local failure, local failure with distant metastasis, distant metastasis, intercurrent disease, and unknown reason was 14, 6, 15, 16 and 0 in LD group, and 13, 24, 30, 9 and 1 in ED group, respectively. The technique and method of combined treatment are described in detail.

Angiosarcoma treated with radiotherapy: impact of tumor type and size on outcome

PURPOSE Angiosarcoma is a rare and highly malignant vascular neoplasm. The purpose of this study was to elucidate the tumor characteristics and evaluate the efficacy of radiotherapy (RT) for angiosarcoma. MATERIALS AND METHODS Thirty patients with angiosarcoma (20 males and 10 females, age range 4-89 years, median 66) who received RT from 1986 to 1999 were enrolled in the study. Twenty-four patients had angiosarcoma of the face and scalp (AFS), and 6 patients had angiosarcomas at other sites. AFS was classified into two categories (according to the macroscopic features): nodular AFS (14 patients) and endophytic AFS (10 patients). The median prescribed irradiation dose was 68 Gy. Surgery had been previously performed in 9 patients, and adjuvant immunotherapy using recombinant interleukin-2 (rIL-2) was combined during and after RT in 20 patients. Univariate analyses and calculation of survival by Kaplan-Meier methods were performed. RESULTS Local tumor control was obtained in 17 patients (57%). However, 7 (47%) of them developed distant metastases. The median survival time for all patients was 8 months (7 months for AFS), and the 13-year overall survival rate was 25% (20% for AFS). Twenty-one patients died of angiosarcoma, with the cause of death local failure in 7 patients, distant failure in 7, and both in 7. Tumor type and size were found to be significant prognostic factors (p = 0.004 and p = 0.007, respectively), and age, total amount of rIL-2, gender, radiation dose, and surgery were not. Six patients (4 with nodular AFS and 2 with angiosarcoma in other parts) survived >2 years. No patient with endophytic AFS survived >2 years. Ten patients (33%) died of respiratory failure secondary to pulmonary metastases. High-dose rIL-2 administration suppressed the occurrence of distant metastases (p = 0.006). Two patients developed radiation dermatitis (Radiation Therapy Oncology Group Grade 4). CONCLUSION RT, combined with complete resection or adjuvant rIL-2 immunotherapy, could be a promising treatment strategy, leading to prolonged survival in patients with angiosarcoma.

High-dose-rate intraluminal brachytherapy (HDRIBT) for esophageal cancer☆

High-dose-rate intraluminal brachytherapy (HDRIBT) for patients with esophageal cancer has been performed with and without external radiotherapy (ERT) in our department since May 1980. From May 1980 through December 1986, 92 patients with esophageal squamous cell carcinoma were treated with HDRIBT following ERT. These patients were divided into a limited disease (LD) group and an extensive disease (ED) group. Complete response and partial response rates after treatment were 48% and 38% in the LD group, and 9% and 65% in the ED group, respectively. The median survival time and 2-year survival rate was 13 months and 39% in the LD group, and 8.5 months and 7% in the ED group, respectively. The 5-year survival was 17% in the LD group. HDRIBT without ERT was used to treat six patients with small, superficial esophageal squamous cell carcinoma from August 1987 through July 1988. No patients were candidates for surgery because of coexisting medical problems. Each patient received 6 Gy per treatment, twice weekly with a total of 24 Gy; five of the six patients were treated on an outpatient basis. The tumor had disappeared completely in all six patients at the time of first follow-up endoscopic study less than 1 month after treatment, and no local recurrence had occurred after 11 to 22 months in five of the six patients. Five of the six patients were alive after 11 to 22 months, and one died with mediastinal metastasis at 15 months.

Japanese Structure Survey of Radiation Oncology in 2005 Based on Institutional Stratification of Patterns of Care Study

PURPOSE To evaluate the structure of radiation oncology in Japan in terms of equipment, personnel, patient load, and geographic distribution to identify and improve any deficiencies. METHODS AND MATERIALS A questionnaire-based national structure survey was conducted between March 2006 and February 2007 by the Japanese Society of Therapeutic Radiology and Oncology. These data were analyzed in terms of the institutional stratification of the Patterns of Care Study. RESULTS The total numbers of new cancer patients and total cancer patients (new and repeat) treated with radiotherapy in 2005 were estimated at approximately 162,000 and 198,000, respectively. In actual use were 765 linear accelerators, 11 telecobalt machines, 48 GammaKnife machines, 64 60Co remote-controlled after-loading systems, and 119 192Ir remote-controlled after-loading systems. The linear accelerator systems used dual-energy function in 498 systems (65%), three-dimensional conformal radiotherapy in 462 (60%), and intensity-modulated radiotherapy in 170 (22%). There were 426 Japanese Society of Therapeutic Radiology and Oncology-certified radiation oncologists, 774 full-time equivalent radiation oncologists, 117 medical physicists, and 1,635 radiation therapists. Geographically, a significant variation was found in the use of radiotherapy, from 0.9 to 2.1 patients/1,000 population. The annual patient load/FTE radiation oncologist was 247, exceeding the Blue Book guidelines level. Patterns of Care Study stratification can clearly discriminate the maturity of structures according to their academic nature and caseload. CONCLUSIONS The Japanese structure has clearly improved during the past 15 years in terms of equipment and its use, although the shortage of manpower and variations in maturity disclosed by this Patterns of Care Study stratification remain problematic. These constitute the targets for nationwide improvement in quality assurance and quality control.

External beam radiotherapy alone or combined with high-dose-rate intracavitary irradiation in the treatment of cancer of the esophagus: Autopsy findings in 35 cases

Autopsy findings of 35 patients, treated with radiotherapy for an esophageal carcinoma, were reviewed. A residual tumor was seen at autopsy in 7 of 16 patients treated with high-dose-rate intracavitary irradiation following external irradiation, in 13 of 14 patients treated with external irradiation of 50 Gy or more, and in all 5 patients treated with external irradiation of less than 50 Gy. Incidence on lymph node metastasis, at autopsy, did not differ between the combined radiotherapy group and the external irradiation groups. However, it correlated with disease stage. It was observed in 11 of 17 patients with Stage 1 and Stage 2 disease, compared to 17 of 18 patients with Stage 3 and Stage 4 disease. Distant organ metastasis, at autopsy, also did not differ between the combined radiotherapy group and the external irradiation groups, and was also correlated with disease stage. It was found in 8 of 17 patients of the patients with Stage 1 and Stage 2 disease, compared to all 18 patients with Stage 3 and Stage 4 disease. Mean (average) survival was different between the patients treated by high-dose-rate intracavitary irradiation following external irradiation and those treated by external irradiation alone; 11.3 months in the 16 patients treated with combined therapy, as compared to 6.9 months in the 14 patients who received external irradiation of 50 Gy or more, and 3.6 months in the 5 patients who received external irradiation of less than 50 Gy.

Radiotherapy for carcinoma of the esophagus in patients aged eighty or older

Between 1980 and 1988, 206 patients with esophageal cancer were treated initially with radiotherapy. The patients were classified into three groups according to age. Ninety-four patients aged 43-69 years comprised Group A, 83 patients aged 70-79 years comprised Group B, and 29 patients aged 80-86 years comprised Group C. There were no statistically significant differences in background factors between Groups A, B, and C, except for the sex ratio. The male:female ratio was 7.5:1 in Group A, 3.9:1 in Group B, and 1.9:1 in Group C, with the difference between Groups A and C being statistically significant (p less than 0.05). High-dose-rate intracavitary irradiation (HDRII) with or without external irradiation (EI) was performed in 64%, 69%, and 83% of the patients from Groups A, B, and C, respectively. Patients in Groups A, B, and C achieved CR in 23%, 24%, and 34% of cases following radiotherapy. Two- and 5-year survival rates were 16.7% and 6.7% in Group A, 17.2% and 6.0% in Group B, and 27.1% and 20.3% in Group C. No significant differences were found in the patterns of failure and in the radiation-induced injuries between the three groups. Our data suggested that radiotherapy was the treatment of first choice for patients 80 years old and older.

The oncoprotein and stem cell renewal factor BMI1 associates with poor clinical outcome in oesophageal cancer patients undergoing preoperative chemoradiotherapy

BackgroundThe polycomb group (PcG) family BMI1, acting downstream of the hedgehog (Hh) pathway, plays an essential role in the self-renewal of haematopoietic, neural, and intestinal stem cells, and is dysregulated in many types of cancer. Our recent report has demonstrated that Hh signalling activation can predict very earlier relapse of oesophageal cancers. As data were not available on the clinical role of BMI1 expression in oesophageal cancers after chemoradiotherapy (CRT), we analysed whether it could be also used to predict disease progression and prognosis in oesophageal cancer patients undergoing trimodality therapy of preoperative CRT and oesophagectomy.MethodsExpressions of BMI1 and p16INK4A, a downstream target of PcG, were analysed in 78 patients with histologically confirmed oesophageal squamous cell carcinoma (ESCC) after preoperative CRT by immunohistochemical staining. The association of BMI1 and p16INK4A expression with clinicopathologic characteristics was analysed by χ2-test. Survival analysis was carried out by the log-rank test using Kaplan-Meier method.ResultsAmong 78 ESCC patients, 24 patients (30.8%) showed BMI1 positivity, mainly localised in the nuclei of tumour cells. Patients harbouring BMI1-positive tumour cells showed significantly poorer prognoses than those without such cells or residual tumours (mean disease-free survival (DFS) time 16.8 vs 71.2 months; 3-yr DFS 13.3% vs 49.9%, P=0.002; mean OS time 21.8 vs 76.6 months; 3-yr OS 16.2% vs 54.9%, P=0.0005). There was no significant correlation between p16INK4A expression and BMI1 expression.ConclusionsOur study shows that BMI1 expression is a predictor of early relapse and poor prognosis in ESCC after CRT. These findings suggest that BMI1 signal activation might be involved in promoting cancer regrowth and progression after CRT, and might be indicative of emergence of ‘more aggressive’ cancer progenitor cells.

Japanese structure survey of radiation oncology in 2009 based on institutional stratification of the Patterns of Care Study

The ongoing structure of radiation oncology in Japan in terms of equipment, personnel, patient load and geographic distribution was evaluated in order to radiation identify and improve any deficiencies. A questionnaire-based national structure survey was conducted from March 2010 to January 2011 by the Japanese Society for Therapeutic Radiology and Oncology (JASTRO). These data were analyzed in terms of the institutional stratification of the Patterns of Care Study (PCS). The total numbers of new cancer patients and total of cancer patients (new and repeat) treated with radiation in 2009 were estimated at 201,000 and 240,000, respectively. The type and numbers of systems in actual use consisted of Linac (816), telecobalt (9), Gamma Knife (46), 60Co remote afterloading system (RALS) (29) and 192Ir RALS systems (130). The Linac systems used dual energy function for 586 (71.8%), 3DCRT for 663 (81.3%) and IMRT for 337 units (41.3%). There were 529 JASTRO-certified radiation oncologists (ROs), 939.4 full-time equivalent (FTE) ROs, 113.1 FTE medical physicists and 1836 FTE radiation therapists. The frequency of interstitial radiation therapy use for prostate and of intensity-modulated radiotherapy increased significantly. PCS stratification can clearly identify the maturity of structures based on their academic nature and caseload. Geographically, the more JASTRO-certified physicians there were in a given area, the more radiation therapy tended to be used for cancer patients. In conclusion, the Japanese structure has clearly improved during the past 19 years in terms of equipment and its use, although a shortage of manpower and variations in maturity disclosed by PCS stratification remained problematic in 2009.

A Feasibility Study of Induction Pemetrexed Plus Cisplatin Followed by Extrapleural Pneumonectomy and Postoperative Hemithoracic Radiation for Malignant Pleural Mesothelioma

A prospective multi-institutional study has been commenced in Japan to evaluate the feasibility of induction chemotherapy using pemetrexed plus cisplatin, followed by extrapleural pneumonectomy (EPP) and postoperative hemithoracic radiation in patients with resectable malignant pleural mesothelioma. The study was initiated on May 2008 and 40 patients will be recruited over 3 years. Primary endpoints are macroscopic complete resection rate by EPP and treatment-related mortality for trimodality therapy. Secondary endpoints include treatment completion rate, adverse events, response rate by chemotherapy and 2-year overall and relapse-free survival.