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. METHODS: Sixty-eight patients with stage I (UICC T1N0M0) esophageal squamous cell carcinoma treated by definitive RT alone were analyzed. Brachytherapy was administered in 36 patients as a boost, and the prescribed doses were 10 Gy (5 Gy x 2 times) at a low dose rate (19 patients) and 9 Gy (3 Gy x 3 times) at a high dose rate (17 patients). Recurrence patterns and survival rates were assessed and the factors predisposing to recurrences after RT were statistically investigated by univariate analysis. RESULTS: The 5-year cause-specific survival rate and the locoregional control rate were 79.9% and 82.1%, respectively. No case of recurrence or disease-related death was observed in any of the patients with mucosal cancer. Among the cases with the cancer invading the submucosa, there were 12 cases with locoregional recurrence and two cases with distant metastases. In cases of submucosal esophageal cancer, the tumor length was the only statistically significant factor predicting locoregional control. The 5-year locoregional control rate in cases with a short length of the tumor (5 cm in length was 57.8% (P = 0.036). Patients treated by additional brachytherapy exhibited better cause-specific survival and locoregional control rates than those receiving external RT alone, however, the addition had no statistically significant influence on the outcome. CONCLUSIONS: RT was a successful treatment for stage I esophageal cancer, and the treatment outcome using RT was nearly comparable to that of surgery. However, it is suggested that chemo-radiation should be considered in inoperable cases of submucosal cancer when the tumor is more than 5 cm in length.

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 x 2 times) with low dose rate (8 patients) and 9 Gy (3 Gy x 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.

Treatment outcome of breast-conserving therapy in patients with positive or close resection margins: Japanese multi institute survey for radiation dose effect.

BACKGROUND: The relationship between a positive resection margin and the risk of ipsilateral breast tumor recurrence (IBTR) is controversial. To evaluate the radiation dose and other factors influencing the ipsilateral breast tumor control (IBTC) in patients with positive or close resection margins after breast conserving surgery (BCS), the Japanese Radiation Oncology Study Group (JROSG) S-99-3 study group conducted a multi-institute survey of these patients. METHODS: The patients with less than 5 mm tumor-free margins after BCS were eligible for this study. A total of 971 patients from 18 institutes were enrolled in the analysis. The final pathological margin status was classified into 3 groups. Radiation doses to the tumor bed were less than 60 Gy in 252 patients, 60 Gy in 456 patients and more than 60 Gy in 233 patients. RESULTS: IBTR was observed in 55 patients (5.8%). The IBTC rates at 5 and 10 years by the Kaplan Meier method were 95.6% and 87.3%, respectively. There was no significant difference in 10-year IBTC rates according to marginal status; 85.9% in positive margin patients, 91.0% in equal or less than 2 mm margin patients and 87.0% in 2.1-5 mm margin patients. Radiation dose to the tumor bed was a marginally significantly associated with the 10-year IBTC rate (> or = 60 Gy 90.8% vs < 60 Gy 84.2%, p = 0.057). In patients with positive margins, IBTC with radiation dose equal to or more than 60 Gy was significantly better (p = 0.039). The other factors influencing the IBTC were age (> or = 35 years vs < 35 years: p < 0.0001), menopausal status (p < 0.0001) and tumor size (p = 0.023). CONCLUSIONS: In patients with positive margins, IBTC with radiation dose equal to or more than 60 Gy was significantly better than the others. We recommend that the tumor bed be irradiated with at least 60 Gy in the patients with positive margins. Further follow-up is necessary to draw final conclusions.

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

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.

Breast-conserving surgery following radiation therapy of 50 Gy in stages I and II carcinoma of the breast: the experience at one institute in Japan.

This study evaluated the results of breast-conserving therapy experienced in one institute. A total of 217 breasts in 215 patients with clinical stages I and II breast cancer undergoing breast-conserving therapy between August 1991 and December 1999 were included. The actuarial 5-year local recurrence-free survival, disease-free survival and overall survival rates were 97.4%, 88.5% and 92.5%, respectively. Microscopic margins were negative in 176 (81.1%) of the total breasts and positive in 41 (18.9%). There were no differences in the age at operation, tumor size, clinical stage, lymph node status, estrogen receptor status, or distance from tumor to nipple between patients with positive surgical margins and with negative surgical margins. During the follow-up period, local recurrence occurred in seven patients. Local recurrence was significantly less frequent in patients with surgical margin-negative tumors than those with surgical margin-positive tumors, and also in ER-positive tumors than ER-negative or ER-unknown tumors. There was no difference in overall survival between patients with and without breast-recurrence. Using multivariate analysis, the surgical margin was determined to be an independent predictive factor for local recurrence in the conserved breast. Nodal status and ER status were independent prognostic factors, but local recurrence did not have an independent negative impact on survival. We conclude that microscopic surgical margin is the most important factor associated with local recurrence in the conserved breast among patients treated with breast-conserving surgery and radiation therapy of 50 Gy. Local recurrence however, has no adverse effect on survival of patients.

Breast-conserving therapy versus modified radical mastectomy in the treatment of early breast cancer in Japan.

BACKGROUND: Breast-conserving therapy has been widely utilized as a treatment option for women with early breast cancer. However, no randomized study comparing modified radical mastectomy and breast-conserving therapy has been conducted in Japan. METHODS: Two hundred and twenty-eight Japanese women with early breast cancer enrolled in the Gunma Breast Conserving Therapy Study between 1991 and 1994 were examined to determine whether there is any difference in disease-free survival or overall survival between radical mastectomy and breast-conserving therapy. After informed consent was obtained, a total of 119 patients underwent breast-conserving therapy and 109 underwent mastectomy. RESULTS: Mastectomy was a more frequently utilized treatment than breast-conserving therapy in patients with clinical stage II lesions, older age, larger tumor size or shorter distance between tumor and nipple. The mean follow-up period for all patients was 81 months (median 86 months). There was no significant difference in overall survival or disease-free survival between breast-conserving therapy and mastectomy even after adjusting for the clinical stage of the disease. A multivariate analysis of tumor size, lymph node status, estrogen receptor status and operation method using the Cox proportion hazard model confirmed that only lymph node status was an independent prognostic factor. CONCLUSION: Breast-conserving therapy is comparable to modified radical mastectomy in overall survival and disease-free survival.

Relationship between cyclin D1 expression and poor radioresponse of murine carcinomas.

PURPOSE: We recently reported that overexpression of epidermal growth factor receptor (EGFR) positively correlated with radioresistance of murine carcinomas. Because cyclin D1 is a downstream sensor of EGFR activation, the present study investigated whether a relationship exists between the extent of cyclin D1 expression and in vivo radiocurability of murine tumors. We further investigated the influence of radiation on cyclin D1 expression and the expression of p27, an inhibitor of the cyclin D1 downstream pathway, as well as the relationship of these molecular determinants to cell proliferation and induced apoptosis in tumors exposed to radiation. METHODS AND MATERIALS: Cyclin D1 expression was assayed in nine carcinomas syngeneic to C3Hf/Kam mice using Western blot analysis. These tumors greatly differed in their radioresponse as assessed by TCD(50). The expression of cyclin D1 and p27 proteins was determined by Western blotting. Cell proliferative activity in tumors was determined by proliferating cell nuclear antigen (PCNA) immunochemistry. The effect of irradiation on the expression of cyclin D1 or p27 proteins and on PCNA positivity was determined in the radiosensitive OCa-I and in the radioresistant SCC-VII tumors. RESULTS: Cyclin D1 expression varied among tumors by 40-fold, and its magnitude positively correlated with poorer tumor radioresponse (higher TCD(50) values). The level of cyclin D1 expression paralleled that of EGFR. A 15-Gy dose reduced constitutive expression of cyclin D1 in the radiosensitive OCa-I tumors, but had no influence on expression of cyclin D1 in the radioresistant SCC-VII tumors. In contrast, 15 Gy increased the expression of p27 in radiosensitive tumors and reduced it in radioresistant tumors. Radiation induced no significant apoptosis or change in the percentage of PCNA-positive (proliferating) cells in SCC-VII tumors with high cyclin D1 levels, but it induced significant apoptosis and a decrease in the percentage of proliferating cells in OCa-I tumors with low cyclin D1 expression. CONCLUSION: Our findings show a positive correlation between cyclin D1 expression and tumor radioresistance. The expression of cyclin D1 and p27 was modified by radiation and was associated with cellular response to radiation, but this depended on the pretreatment level of cyclin D1 expression. These findings may have important clinical implications: The pretreatment assessment of cyclin D1 expression could serve as a useful predictor of radiotherapy outcome and assist in selecting an effective treatment modality.