Hiroshi Kiriu

Optimum fractionation for high-dose-rate endoesophageal brachytherapy following external irradiation of early stage esophageal cancer

PURPOSE To establish the optimum fractionation for high-dose-rate (HDR) endoesophageal brachytherapy (EBT) for early stage esophageal cancer from retrospective data of patients treated with different HDR schedules following external beam irradiation (EBI). METHODS AND MATERIALS The study population consisted of 35 consecutive early stage esophageal cancer patients who received EBI to the mediastinum, plus EBT, between May 1992 and November 1995 at the Hiroshima University Medical Center and Hiroshima City Hospital. All patients were treated with EBI, with doses ranging from 50 to 61 Gy. The spinal cord was spared after 44-45 Gy. HDR EBT was performed using a double-balloon applicator in conjunction with an Ir-192 remote afterloading system. One group of 10 patients was given a weekly endoesophageal boost of 4 or 5 Gy at a distance of 5 mm from the applicator surface over a period of 1-2 weeks. Another group of 25 patients was treated with 4 or 5 endoesophageal boosts with a fraction dose of either 2.5 or 2 Gy for 1 week. The linear quadratic (LQ) formula was used to calculate the biologically effective dose (BED) for tumor (Gy10) and esophageal mucosa (Gy3); Gy10 means alpha/beta equals 10 Gy, and Gy3 means alpha/beta equals 3 Gy. The Kaplan-Meier method was used to calculate the local control and late complication rates, while the Cox-Mantel test was used to evaluate statistical significance (p < 0.01). RESULTS Nine (26%) of the 35 patients recurred locally and 7 (20%) had late complications (esophageal ulcer grade by RTOG/EORTC criteria > 1). The 5-year overall survival, local control, and late complication rates were 38%, 57%, and 26%, respectively. The probability of local recurrence was not affected by the treatment parameters. Results from the LQ formula significantly correlate with data on late complications. A BED > 134 Gy3 and a fraction number = < 3 were associated with late complications (grade > 1). BED analysis showed that the fractionation dose should be decreased to 2.5 or 2.0 Gy at a distance of 5 mm from the applicator surface, and the number of doses increased to 4 or 5, respectively, to yield a satisfactory BED (< 134 Gy3). CONCLUSION A significant reduction in endoesophageal brachytherapy dose per fraction is necessary to reduce late complications. Our current treatment protocol for early-stage esophageal cancer consists of EBI of 60 Gy followed by 4 EBT doses at a fraction dose of 2.5 Gy applied over 1 week.

Interstitial brachytherapy for stage I and II squamous cell carcinoma of the oral tongue: factors influencing local control and soft tissue complications.

PURPOSE Our aim was to study the treatment parameters that influence local control and soft tissue complications (STC) in a series of 207 Stage I and II squamous cell carcinomas of the oral tongue treated by interstitial brachytherapy (BRT) alone (127 patients), or by a combination using external beam irradiation (EBI) (80 patients) between 1980 and 1993. METHODS AND MATERIALS The patient distribution was 93 T1, 72 T2a, and 42 T2b. The prescribed BRT dose at the plane 5 mm from the plane of the radioactive sources was 65-70 Gy in BRT alone, and 50-60 Gy in the combined treatment using EBI. Generally, an EBI dose of 30 Gy was used. No prophylactic neck treatment was performed. RESULTS The 5-year local recurrence-free rate for T1, T2a, and T2b was 92.9%, 81.9%, and 71.8%, respectively (p < 0.05). The lesions of endophytic appearance and those located in the posterior half of the mobile tongue had a significantly lower local control rate than those of other macroscopic appearances (p = 0.02) and those in other localizations (p < 0.01). Most local recurrences (66.7%) occurred within 2 years after treatment. However, 8 of 14 recurrences of T1 and 6 of 15 recurrences among patients treated by BRT alone occurred after 5 years. Statistical analysis showed that, in BRT alone treatment, a dose rate < = 1.0 Gy/h was related to better local control (p = 0.04). There was no significant relationship between BRT dose and local control; however, the incidence of local recurrence was lowest in a BRT dose 65-70 Gy. In the combined treatment, a total dose > 85 Gy (p = 0.01), BRT dose > 55 Gy (p = 0.04), and a dose rate < 0.55 Gy/h (p = 0.03) were significantly related to better local control. The incidence of more severe STC were 11.5% and was significantly higher in T2a (p = 0.03) and T2b (p < 0.01) than in T1. Statistical analysis revealed that a dose rate > = 0.6 Gy/h was significantly related to more STC in BRT alone (p = 0.03), and that a dose rate > = 0.55 Gy/h (p < 0.03) and a BRT dose > 70 Gy ( < 0.05) and a total dose > 100 Gy (p < 0.05) were significantly related to more STC in the combined treatment. Neck metastases occurred in 25% in T1N0, 27% in T2aN0, and 31% in T2bN0 (NS). Eighty-eight percent were found within 12 months. Thirty-three secondary cancers including 12 head and neck, 8 esophageal, and 3 gastric were found after treatment. The 5-year crude survival rate for T1, T2a, and T2b was 83.4%, 66.0%, and 70.9%, respectively. CONCLUSION To acheive better local control and fewer STC, we recommend the following relationships between dose and dose rate. In BRT alone, dose rate should be maintained at < 0.6 Gy/h with a preferable BRT dose 65-70 Gy. In the combined treatment, total dose, BRT dose and dose rate should be kept between > 85 Gy and < = 100Gy, between > 55 Gy and < = 70 Gy, and < 0.55 Gy/h, respectively. We also recommend longer follow-up periods; more than 5 years might be necessary for late local recurrences and for secondary cancers.

An analysis of mandibular bone complications in radiotherapy for T1 and T2 carcinoma of the oral tongue

PURPOSE To examine the incidence of mandibular bone complication in patients who underwent radiotherapy for T1 and T2 carcinomas of the oral tongue and to analyze the factors contributing to its occurrence. METHODS AND MATERIALS The clinical records of 148 patients with T1 and T2 carcinoma of the oral tongue treated with radiotherapy alone between 1978 and 1989 were examined retrospectively. Interstitial brachytherapy, used as the major treatment modality, was performed using cobalt needles, radium needles, or iridium hairpins. The prescribed dose at the plane 5 mm from the plane of the radioactive sources was 65-70 Gy in interstitial brachytherapy alone, and 50-60 Gy in the combined treatment with external irradiation. An external irradiation dose of 30 Gy was usually used. RESULTS Eleven of the patients showed radiation-induced mandibular bone complication. Two (1 T1, 1 T2) had been treated with interstitial brachytherapy alone, and nine (2 T1, 7 T2) with the combination of external irradiation and interstitial brachytherapy. The incidence of radiation complication of bone was significantly higher in the patients with T2 tumors (p = 0.04) and in those who received the combined treatment (p < 0.01). Multivariate analysis revealed that the total dose (p = 0.04) and dose rate of interstitial brachytherapy (p = 0.03) were significant factors contributing to radiation bone complication. A significant difference in the incidence of bone complication was also seen between patients who received a total dose of 90 Gy or more and those who received less than 90 Gy (p < 0.01), as well as between patients who were treated with 0.55 Gy/h or higher and those who were treated with less than 0.55 Gy/h (p = 0.03). CONCLUSION A significant increase in the incidence of bone complication was found at the total dose of 90 Gy or more and at the dose rate of 0.55 Gy/h or higher. In combined treatment with external irradiation and interstitial brachytherapy, the interstitial brachytherapy dose of 60 Gy appears to be the threshold at which mandibular bone complication is induced when the external irradiation dose is 30 Gy.

Treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy for prostate cancer.

BackgroundThe indications for and the efficacy of radiation therapy after radical operation for patients with prostate cancer are not clear. We analyzed the treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy.MethodsBetween September 1997 and November 2004, 57 patients received adjuvant radiotherapy or salvage radiotherapy after radical prostatectomy. Fifteen patients received radiation therapy because of positive margins and/or extracapsular invasion in surgical specimens (adjuvant group). Forty-two patients received radiation therapy because of rising prostate-specific antigen (PSA) during follow-up (salvage group). Radiation therapy was delivered to the fossa of the prostate ± seminal vesicles by a three-dimensional (3-D) conformal technique to a total dose of 60–66 Gy (median, 60 Gy). Biochemical control was defined as the maintenance of a PSA level of less than 0.2 ng/ml.ResultsThe median follow-up period after radiation therapy was 33 months (range, 12–98 months). Three-year biochemical control rates were 87% for the adjuvant group and 61% for the salvage group. For patients in the salvage group treated without hormone therapy, the preradiation PSA value was the most significant factor for the biochemical control rate. The 3-year biochemical control rate was 93% in patients whose preradiation PSA was 0.5 ng/ml or less and 29% in patients whose preradiation PSA was more than 0.5 ng/ml. No severe adverse effects (equal to or more than grade 3) were seen in treated patients.ConclusionRadiation therapy after radical prostatectomy seemed to be effective for adjuvant therapy and for salvage therapy in patients with a preradiation PSA of 0.5 ng/ml or less. Also, radiation to the fossa of the prostate ± seminal vesicles, to a total dose of 60–66 Gy, using a three-dimensional (3-D) conformal technique, seemed to be safe.