Tadayuki Kotsuma

Needle applicator displacement during high-dose-rate interstitial brachytherapy for prostate cancer

PURPOSE To introduce an effective ambulatory technique in high-dose-rate interstitial brachytherapy (HDR-ISBT) for prostate cancer, we investigated the displacement distance using our novel calculation method. METHODS AND MATERIALS Sixty-four patients treated with HDR-ISBT as monotherapy were examined. Of these, 4, 17, and 43 patients were administered treatment doses of 38 Gy (3 days), 49 Gy (4 days), and 54 Gy (5 days), respectively. For dose administration, we used 776 flexible applicators with a removable template (ambulatory technique). Using CT images, we calculated the relative coordinates of the metal markers and applicators. From these coordinates, to analyze displacement during treatment, we measured the distance between the tip of the needle applicator and the center of gravity of the markers along the average applicator vector. RESULTS The median displacement distance for all applicators was 7 mm (range, -14 to 24), and that of each treatment schedule was 4, 6, and 9 mm for 38, 49, and 54 Gy, respectively. Of the 776 applicators, displacement of >10 mm was seen in 198 (26%) applicators and >15 mm in 57 (7%) applicators. Body height (p<0.0001) and anticoagulant usage (p<0.0001) were significant factors influencing displacement. CONCLUSIONS We investigated needle applicator displacement using our unique method. Additional cranial margins are necessary if there is no repositioning of the dwell position. CT scanning should be performed daily during treatment for checking the position of the applicator to detect and rectify the issue of displacement.

CORRELATION BETWEEN DOSIMETRIC PARAMETERS AND LATE RECTAL AND URINARY TOXICITIES IN PATIENTS TREATED WITH HIGH-DOSE-RATE BRACHYTHERAPY USED AS MONOTHERAPY FOR PROSTATE CANCER

PURPOSE To evaluate the correlation between dosimetric parameters and late rectal and urinary toxicities in high-dose-rate brachytherapy (HDR-BT) used as monotherapy for prostate cancer. METHODS AND MATERIALS The data of 83 patients treated with HDR-BT alone for prostate cancer from 2001 through 2005 at Osaka University Hospital were analyzed. Median follow-up time was 36 months (range, 18-70). The total prescribed dose was 54 Gy in nine fractions over 5 days. Correlation between dosimetric parameters and late toxicities was examined. RESULTS The means of V30, V40, V50, V60, V70, D1cc, D2cc, D5cc, and D10cc of the rectum were significantly higher in 18 patients who presented with late rectal toxicity (Grades 1-3 rectal bleeding) than in the other 65 patients who did not. A significant difference was observed for D1cc-10cc but not for D5-90. The statistically most significant difference was observed for V40 and D5cc. Late rectal toxicity rate was significantly higher for patients with rectal V40 >or= 8 cc than those with the rectal V40 < 8 cc (42% vs. 8%; p < 0.001), as well as for patients with rectal D5cc >or= 27 Gy compared with those with rectal D5cc < 27 Gy (50% vs. 11%; p < 0.001). Dosimetric parameters of the urethra of 15 patients with late urinary toxicity were not significantly different from the 68 patients without toxicity. CONCLUSION Rectal V40 < 8 cc and D5cc < 27 Gy may be dose-volume constraints in HDR-BT used as monotherapy for prostate cancer.

A Dose–Volume Analysis of Magnetic Resonance Imaging-Aided High-Dose-Rate Image-Based Interstitial Brachytherapy for Uterine Cervical Cancer

PURPOSE To investigate the feasibility of our novel image-based high-dose-rate interstitial brachytherapy (HDR-ISBT) for uterine cervical cancer, we evaluated the dose-volume histogram (DVH) according to the recommendations of the Gynecological GEC-ESTRO Working Group for image-based intracavitary brachytherapy (ICBT). METHODS AND MATERIALS Between June 2005 and June 2007, 18 previously untreated cervical cancer patients were enrolled. We implanted magnetic resonance imaging (MRI)-available plastic applicators by our unique ambulatory technique. Total treatment doses were 30-36 Gy (6 Gy per fraction) combined with external beam radiotherapy (EBRT). Treatment plans were created based on planning computed tomography with MRI as a reference. DVHs of the high-risk clinical target volume (HR CTV), intermediate-risk CTV (IR CTV), and the bladder and rectum were calculated. Dose values were biologically normalized to equivalent doses in 2-Gy fractions (EQD(2)). RESULTS The median D90 (HR CTV) and D90 (IR CTV) per fraction were 6.8 Gy (range, 5.5-7.5) and 5.4 Gy (range, 4.2-6.3), respectively. The median V100 (HR CTV) and V100 (IR CTV) were 98.4% (range, 83-100) and 81.8% (range, 64-93.8), respectively. When the dose of EBRT was added, the median D90 and D100 of HR CTV were 80.6 Gy (range, 65.5-96.6) and 62.4 Gy (range, 49-83.2). The D(2cc) of the bladder was 62 Gy (range, 51.4-89) and of the rectum was 65.9 Gy (range, 48.9-76). CONCLUSIONS Although the targets were advanced and difficult to treat effectively by ICBT, MRI-aided image-based ISBT showed favorable results for CTV and organs at risk compared with previously reported image-based ICBT results.

Quantitative assessment of inter-observer variability in target volume delineation on stereotactic radiotherapy treatment for pituitary adenoma and meningioma near optic tract

BackgroundTo assess inter-observer variability in delineating target volume and organs at risk in benign tumor adjacent to optic tract as a quality assurance exercise.MethodsWe quantitatively analyzed 21 plans made by 11 clinicians in seven CyberKnife centers. The clinicians were provided with a raw data set (pituitary adenoma and meningioma) including clinical information, and were asked to delineate the lesions and create a treatment plan. Their contouring and plans (10 adenoma and 11 meningioma plans), were then compared. In addition, we estimated the influence of differences in contouring by superimposing the respective contours onto a default plan.ResultsThe median planning target volume (PTV) and the ratio of the largest to the smallest contoured volume were 9.22 cm3 (range, 7.17 - 14.3 cm3) and 1.99 for pituitary adenoma, and 6.86 cm3 (range 6.05 - 14.6 cm3) and 2.41 for meningioma. PTV volume was 10.1 ± 1.74 cm3 for group 1 with a margin of 1 -2 mm around the CTV (n = 3) and 9.28 ± 1.8 cm3(p = 0.51) for group 2 with no margin (n = 7) in pituitary adenoma. In meningioma, group 1 showed larger PTV volume (10.1 ± 3.26 cm3) than group 2 (6.91 ± 0.7 cm3, p = 0.03). All submitted plan keep the irradiated dose to optic tract within the range of 50 Gy (equivalent total doses in 2 Gy fractionation). However, contours superimposed onto the dose distribution of the default plan indicated that an excessive dose 23.64 Gy (up to 268% of the default plan) in pituitary adenoma and 24.84 Gy (131% of the default plan) in meningioma to the optic nerve in the contours from different contouring.ConclusionQuality assurance revealed inter-observer variability in contour delineation and their influences on planning for pituitary adenoma and meningioma near optic tract.

Frequency, outcome and prognostic factors of carotid blowout syndrome after hypofractionated re-irradiation of head and neck cancer using CyberKnife: A multi-institutional study

PURPOSE Re-irradiation has attracted attention as a potential therapy for recurrent head and neck tumors. However, carotid blowout syndrome (CBS) has become a serious complication of re-irradiation because of the associated life-threatening toxicity. Determining of the characteristics of CBS is important. We conducted a multi-institutional study. METHODS AND PATIENTS Head and neck carcinoma patients (n=381) were treated with 484 re-irradiation sessions at 7 Japanese CyberKnife institutions between 2000 and 2010. RESULTS Of these, 32 (8.4%) developed CBS, which proved fatal that median survival time after CBS onset was 0.1 month, and the 1-year survival rate was 37.5%. The median duration between re-irradiation and CBS onset was 5 months (range, 0-69 months). Elder age, skin invasion, and necrosis/infection were identified as statistically significant risk factors after CBS by univariate analysis. The presence of skin invasion at the time of treatment found only in postoperative case, is identified as only statistically significant prognostic factor after CBS in multivariate analysis. The 1-year survival rate for the group without skin invasion was 42%, whereas no patient with skin invasion survived more than 4 months (0% at 1 year, p=0.0049). CONCLUSIONS Careful attention should be paid to the occurrence of CBS if the tumor is located adjacent to the carotid artery. The presence of skin invasion at CBS onset is ominous sign of lethal consequences.

Daily computed tomography measurement of needle applicator displacement during high-dose-rate interstitial brachytherapy for previously untreated uterine cervical cancer

PURPOSE We investigated daily needle applicator displacement during high-dose-rate interstitial brachytherapy. METHODS AND MATERIALS Ten patients with previously untreated uterine cervical cancer received 30Gy in five fractions during 3 days of high-dose-rate interstitial brachytherapy combined with external beam radiotherapy using our unique ambulatory technique. To analyze displacement, we obtained daily computed tomography (CT) images for 147 flexible needle applicators at 21 and 45h after implantation. The distance was defined as the length between the center of gravity of titanium markers and the needle applicator tips along the daily CT axis. We adapted dwell positions of the treatment source to cover clinical target volume with a 15-mm cranial margin. RESULTS The median displacement was 1mm (range, -6 to 12mm) at 21h and 2mm (range, -9 to 14mm) at 45h, respectively. Statistically significant caudal displacement was observed only between the displacement at 0 and 21h (p<0.0001), and not between the displacement at 21 and 45h (p=0.1). In cases with displacement of 3mm or more, we changed dwell positions to correct the treatment plan. We corrected 45 applicators (31%) at 21h and 67 (46%) at 45h. CONCLUSIONS We investigated needle applicator displacement in our ambulatory technique using daily CT examination and considered that a 15-mm cranial margin was sufficient to cover clinical target volume.

High-dose-rate interstitial brachytherapy for previously untreated cervical carcinoma

PURPOSE The aim of the study was to evaluate the results of high-dose-rate interstitial brachytherapy (HDR-ISBT) for patients with advanced cervical carcinoma in which intracavitary radiation therapy may result in a suboptimal dose distribution. METHODS AND MATERIALS Between 1995 and 2005, 25 patients of median age 64 years were treated with external beam radiation therapy and HDR-ISBT. The International Federation of Gynecology and Obstetrics stages of the patients were I (4%), II (16%), III (68%), and IVA (12%). Whole pelvic irradiation of 30Gy/15 fractions was followed by HDR-ISBT of 30Gy/5 fractions/3 days. Subsequently, additional pelvic external beam radiation therapy of 20Gy/10 fractions was delivered with a midline block. The median followup period was 55 months. RESULTS The actuarial 5-year progression-free survival and overall survival rates for all cases were 42% and 54%, respectively. For the 17 patients with a Stage III tumor, the 5-year local control and overall survival rates were 73% and 51%, respectively. Two patients (8%) developed late toxicities of Grade 3. CONCLUSIONS A high rate of pelvic control and survival with acceptable level of late toxicities were obtained for patients with advanced cervical carcinoma treated with HDR-ISBT.

Carotid blowout syndrome in pharyngeal cancer patients treated by hypofractionated stereotactic re-irradiation using CyberKnife: A multi-institutional matched-cohort analysis

BACKGROUND AND PURPOSE Although reirradiation has attracted attention as a potential therapy for recurrent head and neck tumors with the advent of modern radiotherapy, severe rate toxicity such as carotid blowout syndrome (CBOS) limits its potential. The aim of this study was to identify the risk factors of CBOS after hypofractionated stereotactic radiotherapy (SBRT). METHODS AND PATIENTS We conducted a matched-pair design examination of pharyngeal cancer patients treated by CyberKnife reirradiation in four institutes. Twelve cases with CBOS were observed per 60 cases without CBOS cases. Prognostic factors for CBOS were analyzed and a risk classification model was constructed. RESULTS The median prescribed radiation dose was 30 Gy in 5 fractions with CyberKnife SBRT after 60 Gy/30 fractions of previous radiotherapy. The median duration between reirradiation and CBOS onset was 5 months (range, 0-69 months). CBOS cases showed a median survival time of 5.5 months compared to 22.8 months for non-CBOS cases (1-year survival rate, 36% vs.72%; p=0.003). Univariate analysis identified an angle of carotid invasion of >180°, the presence of ulceration, planning treatment volume, and irradiation to lymph node areas as statistically significant predisposing factors for CBOS. Only patients with carotid invasion of >180° developed CBOS (12/50, 24%), whereas no patient with tumor involvement less than a half semicircle around the carotid artery developed CBOS (0/22, 0%, p=0.03). Multivariate Cox hazard model analysis revealed that the presence of ulceration and irradiation to lymph nodes were statistically significant predisposing factors. Thus, we constructed a CBOS risk classification system: CBOS index=(summation of risk factors; carotid invasion >180°, presence of ulceration, lymph node area irradiation). This system sufficiently separated the risk groups. CONCLUSION The presence of ulceration and lymph node irradiation are risk factors of CBOS. The CBOS index, including carotid invasion of >180°, is useful in classifying the risk factors and determining the indications for reirradiation.

Hypofractionated Stereotactic Radiation Therapy in Three to Five Fractions for Vestibular Schwannoma

OBJECTIVE To retrospectively examine the outcomes of hypofractionated stereotactic radiation therapy in three to five fractions for vestibular schwannomas. METHODS Twenty-five patients with 26 vestibular schwannomas were treated with hypofractionated stereotactic radiation therapy using a CyberKnife. The vestibular schwannomas of 5 patients were associated with type II neurofibromatosis. The median follow-up time was 80 months (range: 6-167); the median planning target volume was 2.6 cm(3) (0.3-15.4); and the median prescribed dose (≥D90) was 21 Gy in three fractions (18-25 Gy in three to five fractions). Progression was defined as ≥2 mm 3-dimensional post-treatment tumor enlargement excluding transient expansion. Progression or any death was counted as an event in progression-free survival rates, whereas only progression was counted in progression-free rates. RESULTS The 7-year progression-free survival and progression-free rates were 78 and 95%, respectively. Late adverse events (≥3 months) with grades based on Common Terminology Criteria for Adverse Events, v4.03 were observed in 6 patients: Grade 3 hydrocephalus in one patient, Grade 2 facial nerve disorders in two and Grade 1-2 tinnitus in three. In total, 12 out of 25 patients maintained pure tone averages ≤50 dB before hypofractionated stereotactic radiation therapy, and 6 of these 12 patients (50%) maintained pure tone averages at this level at the final audiometric follow-up after hypofractionated stereotactic radiation therapy. However, gradient deterioration of pure tone average was observed in 11 of these 12 patients. The mean pure tone averages before hypofractionated stereotactic radiation therapy and at the final follow-up for the aforementioned 12 patients were 29.8 and 57.1 dB, respectively. CONCLUSIONS Treating vestibular schwannomas with hypofractionated stereotactic radiation therapy in three to five fractions may prevent tumor progression with tolerable toxicity. However, gradient deterioration of pure tone average was observed.

Significance of Tumor Volume Related to Peritumoral Edema in Intracranial Meningioma Treated with Extreme Hypofractionated Stereotactic Radiation Therapy in Three to Five Fractions

BACKGROUND To investigate the treatment results of intracranial meningiomas treated with hypofractionated stereotactic radiation therapy in three to five fractions. METHODS Thirty-one patients (32 lesions) with intracranial meningioma were treated with hypofractionated stereotactic radiation therapy in three to five fractions using CyberKnife. Fifteen lesions were diagnosed as Grade I (World Health Organization classification) by surgical resection and 17 lesions were diagnosed as meningioma based on radiological findings. The median follow-up time was 48 months. The median planning target volume was 6.3 cm(3) (range, 1.4-27.1), and the prescribed dose (D90≤) ranged from 21 to 36 Gy (median, 27.8) administrated in three to five fractions. RESULTS Five-year overall and progression-free survival rate of all 31 patients with intracranial meningioma was 86 and 83%, respectively. Five-year progression-free rate of all 32 lesions was 87%. Six of the 31 patients (19%) developed marked peritumoral edema, three of whom were asymptomatic and three symptomatic, the latter with late adverse effects of more than or equal to Grade 3. The mean planning target volume of the six lesions with marked peritumoral edema was 15.6 cm(3), and for the remaining 26 lesions without marked peritumoral edema was 7.1 cm(3) (P = 0.004). The threshold diameter of 2.56 cm for meningioma was calculated from the planning target volume (11 cm(3)) and was used as marker of developing peritumoral edema (P = 0.003). CONCLUSIONS Tumor volume is a significant indicative factor for peritumoral edema in intracranial meningioma treated with hypofractionated stereotactic radiation therapy in three to five factions.