Kimishige Shimizutani

Phase III trial of high- vs. low-dose-rate interstitial radiotherapy for early mobile tongue cancer.

PURPOSE Oral tongue carcinomas are highly curable with radiotherapy. In the past, patients with tongue carcinoma have usually been treated with low dose rate (LDR) interstitial radiation. This Phase III study was designed to compare the treatment results obtained with LDR with those obtained with high dose rate (HDR) interstitial radiotherapy for tongue carcinoma. METHODS AND MATERIALS The criteria for patient selection for the Phase III study were: (a) presence of a T1T2N0 tumor that could be treated with single-plane implantation, (b) localization of tumor at the lateral tongue border, (c) tumor thickness of 10 mm or less, (d) performance status between O and 3, and (e) absence of any severe concurrent disease. From April 1992 through December 1993, 15 patients in the LDR group (70 Gy/4 to 9 days) and 14 patients in the HDR group (60 Gy/10 fractions/6 days) were accrued. The time interval between two fractions of the HDR brachytherapy was more than 6 h. RESULTS Local recurrence occurred in two patients treated with LDR brachytherapy but in none of the patients treated with HDR. One- and 2-year local control rates for patients in the LDR group were both 86%, compared with 100% in the HDR group (p = 0.157). There were four patients with nodal metastasis in the LDR group and three in the HDR group. Local recurrence occurred in two of the four patients with nodal metastases in the LDR group. One- and 2-year nodal control rates for patients in the LDR group are were 85%, compared with 79% in the HDR group. CONCLUSION HDR fractionated interstitial brachytherapy can be an alternative to traditional LDR brachytherapy for early tongue cancer and eliminate the radiation exposure for medical staffs.

Results of low- and high-dose-rate interstitial brachytherapy for T3 mobile tongue cancer

PURPOSE To evaluate the treatment results of low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy (ISBT) for T3 mobile tongue cancer. MATERIAL AND METHODS Between 1974 and 1992, 61 patients with T3 mobile tongue cancer were treated with LDR ISBT using (192)Ir hairpins with or without single pins. In addition, between 1991 and 1999, 14 patients were treated with HDR ISBT. For nine patients treated with ISBT alone, the total dose was 59-94 Gy (median 72 Gy) within one week in LDR ISBT and 60 Gy/10 fractions/5 days in HDR ISBT. For 66 patients treated with a combination therapy of external beam radiotherapy (EBRT) and ISBT, the total dose was 12.5-60 Gy (median 30 Gy) of EBRT and 50-112 Gy (median 68 Gy) within 1 week in LDR ISBT or 32-60 Gy (median 48 Gy)/8-10 fractions/5-7 days in HDR ISBT. RESULTS The 2- and 3-year local control rates of all patients were both 68%. The 2- and 3-year local control rates of patients treated with LDR ISBT were both 67%, and those with HDR ISBT were both 71%. The local control rate of patients treated with HDR ISBT was similar to those with LDR ISBT. CONCLUSIONS ISBT for T3 mobile tongue cancer is effective and acceptable. The treatment result of HDR ISBT is almost similar to that of LDR ISBT for T3 mobile tongue cancer.

LYMPH NODE METASTASIS OF EARLY ORAL TONGUE CANCER AFTER INTERSTITIAL RADIOTHERAPY

PURPOSE To examine the prognostic factors for lymph node metastasis after brachytherapy for early (T1-T2N0M0) oral tongue cancer. METHODS AND MATERIALS We reviewed the records of 571 patients (500 low dose rate and 71 high dose rate) treated at Osaka University Hospital between 1967 and 1999. RESULTS Patients with lymph node metastasis had tumor with an average diameter of 26 +/- 8 mm and a thickness of 9 +/- 5 mm; for patients without lymph node metastasis, the corresponding dimensions were 23 +/- 8 mm and 7.5 +/- 4 mm (p = 0.0004 and 0.001, respectively). After 5 years, the ulcerative (48%) and indurative/infiltrative (39%) types showed a higher ratio of nodal involvement than the exophytic (31%) and superficial (19%) types (p <0.0001). Multivariate analysis showed ulceration (p = 0.006) and a thickness of <or =6 mm (p = 0.04) to be statistically significant predisposing factors for lymph node metastasis. The lymph node control rate was 68% in 1967-1979, 71% in 1980-1990, and 66% in 1990-1999; the corresponding successful salvage rates for lymph node metastasis were 43%, 33%, and 58% (p = 0.04). CONCLUSION The appearance of the tumor, especially the presence or absence of ulceration and the diameter and thickness, are useful prognostic indicators for lymph node metastasis. Although the rates of lymph node metastasis did not change, the salvage outcome for recurrence after interstitial radiotherapy has recently improved.

High dose rate versus low dose rate interstitial radiotherapy for carcinoma of the floor of mouth

PURPOSE Patients with cancer of the floor of mouth are treated with radiation because of functional and cosmetic reasons. We evaluate the treatment results of high dose rate (HDR) and low dose rate (LDR) interstitial radiation for cancer of the floor of mouth. METHODS AND MATERIALS From January 1980 through March 1996, 41 patients with cancer of the floor of mouth were treated with LDR interstitial radiation using 198Au grains, and from April 1992 through March 1996 16 patients with HDR interstitial radiation. There were 26 T1 tumors, 30 T2 tumors, and 1 T3 tumor. For 21 patients treated with interstitial radiation alone, a total radiation dose of interstitial therapy was 60 Gy/10 fractions/6-7 days in HDR and 85 Gy within 1 week in LDR. For 36 patients treated with a combination therapy, a total dose of 30 to 40 Gy of external radiation and a total dose of 48 Gy/8 fractions/5-6 days in HDR or 65 Gy within 1 week in LDR were delivered. RESULTS Two- and 5-year local control rates of patients treated with HDR interstitial radiation were 94% and 94%, and those with LDR were 75% and 69%, respectively. Local control rate of patients treated with HDR brachytherapy was slightly higher than that with 198Au grains (p = 0.113). For late complication, bone exposure or ulcer occurred in 6 of 16 (38%) patients treated with HDR and 13 of 41 (32%) patients treated with LDR. CONCLUSION HDR fractionated interstitial brachytherapy can be an alternative to LDR brachytherapy for cancer of the floor of mouth and eliminate radiation exposure for the medical staff.

Radiotherapy of early tongue cancer in patients less than 40 years old

PURPOSE To evaluate the results of treatment for early mobile tongue cancer in patients less than 40 years. METHODS AND MATERIALS Between January 1967 and September 1992, 70 patients less than 40 years old (young age group) with early tongue cancer (T1-2N0M0) were treated with low-dose-rate (LDR) interstitial radiotherapy at the Osaka University Hospital (OUH). All patients had a minimum 2-year follow-up (median: 13 years). External radiotherapy (median: 30 Gy) was combined in 25 cases. The treatment results were compared with those for two older age groups (middle age: 40-64 years old; old age: 65 years old or more). RESULTS The 5-year probability of cause-specific survival (CSS) rate for the young age group was 80%, which was not significantly different from the two older groups: 81% for middle age and 71% for old age. However, male patients of young age showed significantly worse rates than those of middle and old age (p = 0.02). The 5-year local control rate for the young age group was 78%. It was not significantly different from the two older groups: 81% for middle age and 70% for old age. The incidence of regional lymph node metastasis was 32% for T1, 48% for T2, 56% for males, and 24% for females. The regional failure rate of young males was significantly higher than those of the two older groups: 32% for middle and 22% for old age (p = 0.001). CONCLUSION The overall treatment results for patients with early tongue cancer less than 40 years old were not worse than those of older age groups. However, male gender was a risk factor for lymph node metastasis and CSS.

High dose rate brachytherapy for oral cancer

Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer.

Influence of age on the results of brachytherapy for early tongue cancer

PURPOSE To determine the influence of elder age on the results of brachytherapy for early (T1-2 N0 M0) oral tongue cancer and examine the compatibility of low-dose rate (LDR) with high-dose rate (HDR) brachytherapy. METHODS AND MATERIALS We analyzed 591 patients treated at Osaka University Hospital between 1967 and 1999. We compared the results of radiotherapy for 156 elderly patients (137 LDR and 19 HDR) 65 years of age or older and 435 patients (383 LDR and 52 HDR) less than 65 years of age. RESULTS HDR brachytherapy showed the same local control rate as LDR brachytherapy (81% at 3 years). Elderly patients showed a poorer local control rate (75% at 3 years) than the younger group (83% at 3 years)(p = 0.002). Multivariate analysis identified age as the only prognostic factor for local control (p = 0.002). CONCLUSIONS HDR brachytherapy achieved the same result as LDR brachytherapy. However, the elderly patient showed a higher rate of local recurrence after brachytherapy.

Results of combined external irradiation and chemotherapy of bleomycin or peplomycin for squamous cell carcinomas of the lower gingiva

PURPOSE In Japan, the role of radiotherapy for gingival carcinomas has not been considered as a radical treatment, but only a pre and/or postoperative treatment. This study was aimed to discuss a possibility of radiotherapy for a radical treatment. In this study, radiotherapy was given as an initial treatment for squamous cell carcinomas of the lower gingiva in simultaneous combination with chemotherapy of bleomycin or peplomycin (Tokyo, Japan). METHODS AND MATERIALS When complete regression of the tumor was obtained, subsequent surgery was postponed with or without a booster of radiotherapy of about 30 Gy until a recurrent lesion was confirmed. RESULTS Sixty-seven percent of 100 patients with T1 or T2 had complete regression, while only 22 (35.5%) of 62 patients with T3 or T4 had complete regression. The 5-year local control rate by T classification, including the results of secondary treatments (surgery and/or radiotherapy and/or chemotherapy) for recurrent lesions, was 91% for T1, 89% for T2, 76% for T3 and 61% for T4. The 5-year local control rate according to treatment methods was 95% in the group without surgery and 86% in the group with surgery for T1 and T2 patients. The rates were 54% and 71%, respectively for T3 and T4 patients. The cause specific 5-year survival rate by stage was 75% for Stage I, 87% for Stage II, 71% for Stage III, 51% for Stage IV and 70% overall. CONCLUSION The combination of radiotherapy and chemotherapy could be a conservative radical treatment for T1 and T2 patients with lower gingival carcinoma.

Dose reduction trial from 60 Gy in 10 fractions to 54 Gy in 9 fractions schedule in high-dose-rate interstitial brachytherapy for early oral tongue cancer

To compare the effects of 60 Gy/10 fractions (twice a day) with those of 54 Gy/9 fractions in high-dose-rate interstitial brachytherapy (HDR-ISBT) for early tongue cancer, we performed a matched-pair analysis of patients with early tongue cancer (T1-2N0M0), who were treated with 60 or 54 Gy of radiation between 1996 and 2004. Seventeen patients treated with 54 Gy and 34 matched-pair patients treated with 60 Gy were extracted and analyzed. Local recurrence occurred in two patients in the 54-Gy arm and five patients in the 60-Gy arm. The 2-year local control rates were 88% for both the 54-Gy arm and 60-Gy arm (not significant). The 2-year overall survival rates were 88% in the 60-Gy arm and 82% in the 54-Gy arm. Two-year actuarial complication-free rates were 91% in the 60-Gy arm and 83% in the 54-Gy arm (not significant), respectively. There was no significant association between the total dose and local control rate and late complications. The outcome of 54 Gy/ 9 fractions was similar to that of 60 Gy/ 10 fractions in patients with early tongue cancer.

Age is not a limiting factor for brachytherapy for carcinoma of the node negative oral tongue in patients aged eighty or older

BackgroundTo examine the role of brachytherapy for aged patients 80 or more in the trend of rapidly increasing number.MethodsWe examined the outcomes for elderly patients with node negative oral tongue cancer (T1-3N0M0) treated with brachytherapy. The 21 patients (2 T1, 14 T2, and 5 T3 cases) ranged in age from 80 to 89 years (median 81), and their cancer was pathologically confirmed. All patients underwent definitive radiation therapy, with low dose rate (LDR) Ra-226 brachytherapy (n = 4; median 70Gy), with Ir-192 (n = 12; 70Gy), with Au-198 (n = 1) or with high dose rate (HDR) Ir-192 brachytherapy (n = 4; 60 Gy). Eight patients also underwent external radiotherapy (median 30 Gy). The period of observation ranged from 13 months to 14 years (median 2.5 years). We selected 226 population matched younger counterpart from our medical chart.ResultsDefinitive radiation therapy was completed for all 21 patients (100%), and acute grade 2-3 mucositis related to the therapy was tolerable. Local control (initial complete response) was attained in 19 of 21 patients (90%). The 2-year and 5-year local control rates were 91%, (100% for T1, 83% for T2 and 80% for T3 tumors after 2 years). These figures was not inferior to that of younger counterpart (82% at 5-year, n.s.). The cause-specific survival rate was 83% and the regional control rate 84% at the 2-years follow-up. However, 12 patients died because of intercurrent diseases or senility, resulting in overall survival rates of 55% at 2 years and 34% at 5 years.ConclusionAge is not a limiting factor for brachytherapy for appropriately selected elderly patients, and brachytherapy achieved good local control with acceptable morbidity.