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This study presents multi-institutional individual data of reirradiation (ReRT) for head and neck cancer using brachytherapy (ReRT-BT) collected by national surveillance in Japan.We distributed an e-mail-based questionnaire to 153 institutions equipped with high-dose-rate (HDR) brachytherapy facilities and received responses from 76 institutions (49.7%). Of these 76 institutions, only four (5.2%) performed ReRT-BT for head and neck cancers, and three provided individual patient's data.Six ReRT-BT cases of patients with recurrent head and neck cancer, treated with HDR brachytherapy in seven ReRT sessions, were identified from three institutions. Three patients (two cases of lips and one case of gingiva) who underwent curative-intent treatment achieved complete response at the treated area. Three patients who received palliative treatment (one case of tongue and two cases of maxillary sinus) had sustained tumor growth at the treated site, but with improvement in symptoms. No grade ≥3 toxicity was found after HDR ReRT-BT.ReRT-BT for head and neck cancer using HDR brachytherapy is a safe and useful approach to treat recurrent cancer after initial radiotherapy with curative and palliative intent. However, the scarce availability of ReRT-BT is a barrier to the wider utility of this effective procedure.

Purpose The purpose of this study was to examine the influence of transitioning treatment planning techniques in high-dose-rate interstitial brachytherapy monotherapy for localized prostate cancer. Methods and Materials We compared 113 patients treated with initial two-dimensional treatment planning (2D: 74% received 54 Gy/nine fractions) to 240 patients treated with three-dimensional planning (3D: 70 CT image-guided 3D [CT-3D]: 84% 45.5 Gy/seven fractions and 170 MRI image-guided [MRI-3D]: 87% received 49 Gy/nine fractions). Results The actuarial 5-year biochemical failure-free survival rates for 2D and 3D planning were 88.4% and 95.1% (p = 0.0285 between 2D and 3D) (89.4% in CT-3D and 97.5% in MRI-3D), respectively; the rates for 2D and 3D planning were not available and 100% in the low-risk group (100% and 100%), 97.7% and 94.5% (p = 0.7626) (85.1% and 100%) in the intermediate-risk group, and 82.5% and 94.4% (p = 0.0507) (93.8% and 94.7%) for the high-risk group. Late gastrointestinal (GI) toxicity Grade 1, Grade 2, and Grade 3 was found in 13%, 4%, and 1% in 2D, whereas 8%, 2%, and 0% in 3D group (p = 0.0699), respectively. 3D decreased GI toxicity Grade 2 ≤ than 2D (19% and 10%, p = 0.0169). Late genitourinary toxicity Grade 1, Grade 2, and Grade 3 was 21%, 12%, and 3% for 2D and 32%, 18%, and 3% for 3D, respectively (p = 0.0217). Conclusions The 3D technique has the potential to reduce GI toxicity and improve biochemical control rate compared to 2D planning, whereas 3D resulted in increased mild genitourinary toxicity.

Background To compare the outcome of high-dose-rate interstitial brachytherapy (HDR-BT) monotherapy and low-dose-rate brachytherapy (LDR-BT) with or without external beam radiotherapy (EBRT) for localized prostate cancer. Methods and materials We compared 352 patients treated with HDR-BT as monotherapy (median follow-up time 84 months, NCCN risk classification; low: intermediate: high = 28:145:179) and 486 patients with LDR-BT with or without EBRT (90 months, 194:254:38). HDR-BT treated advanced disease with more hormonal therapy than LDR-BT. LDR-BT excluded patients with T3b–T4 tumor and initial PSA >50 ng/ml. Inverse probability of treatment weighting (IPTW) involving propensity scores was used to reduce background selection bias. Results The actuarial 5-year biochemical failure-free survival rates (bNED) were 92.9% and 95.6% (p = 0.25) in the HDR-BT and LDR-BT groups, respectively, and it was 100% and 97.3% (p = 0.99) in the low-risk, 95.6% and 94.3% (p = 0.19) in the intermediate, 89.6% and 94.9% (p = 0.26) in the high-risk groups, and 93.1% and 94.9% (p = 0.98) in selected high-risk group excluding T3b-4 and initial PSA ≥50. IPTW correction also indicated no difference in bNED between LDR-BT and HDR-BT groups. LDR-BT showed a higher incidence of genitourinary (GU) toxicity grade ≥2 than that of HDR-BT in the acute phase and grade 1 toxicity in late phase. Acute GU toxicity grade ≥1 predicted late GU toxicity grade ≥2. External beam radiotherapy plus LDR-BT elevated GI toxicity than LDR-BT only group. Accumulated incidence of late grade ≥2 GU and GU toxicity was equivalent between HDR-BT and LDR-BT. No grade 4 or 5 toxicities were detected in either modality. Conclusion HDR-BT monotherapy showed an equivalent outcome to that of LDR-BT with or without EBRT for low-, intermediate- and selected high-risk patients. LDR-BT showed equivalent incidence of grade ≥2 late GI and GU toxicities and higher grade ≥2 acute GU toxicity as that of HDR-BT as a monotherapy.

Background Herein, we report the outcomes of 3 schedules of high-dose-rate interstitial brachytherapy (HDR-BT) monotherapy for localized prostate cancer. Patients and methods A total of 347 patients were treated with 45.5 Gy/7 fractions (n = 86; 45.5 Gy arm, median follow-up time 131 months), 49 Gy/7 fractions (n = 149; 49 Gy arm, 75.9 months), and 54 Gy/9 fractions (n = 112; 54 Gy arm, 68 months). Results The actuarial 5-year biochemical failure-free survival rates were 86.8%, 94.1%, and 88.5% (p = 0.2023) for the 45.5 Gy, 49 Gy, and 54 Gy arms in the high-risk group; 90.4%, 100%, and 97.4% (p = 0.0818) in the intermediate-risk group; and not available, 100%, and 100% in the low-risk group, respectively. The 5-year distant metastasis-free (and overall) survival rates were 94.4%, 98.2%, and 96.3% (100%, 92.8%, and 99.1%) for the 45.5 Gy, 49 Gy, and 54 Gy arms (p = 0.5454 and p = 0.0028), respectively. At 5 years, accumulated incidence of grade ≥2 gastrointestinal toxicity was 1.2%, 2.7%, and 3.4% for the 45.5 Gy, 49 Gy, and 54 Gy arms (p = 0.5605), respectively. For genitourinary toxicity, the 49 Gy arm showed a higher grade ≥2 toxicity of 20.5% than those observed in the 45.5 Gy (2.4%) and 54 Gy arms (10.1%). No grade 4 or 5 of either type of toxicity was detected. Conclusions The 3 schedules showed equivocal outcomes in each risk group, with different toxicity profiles. HDR-BT monotherapy with these schedules is an acceptable treatment option for localized prostate cancer.

Purpose To choose the optimal brachytherapeutic modality for uterine cervical cancer, we performed simulation analysis. Methods and Materials For each high-risk clinical target volume (HR CTV), we compared four modalities [classical conventional intracavitary brachytherapy ( Conv ICBT), Image-guided ICBT (IGICBT), intracavitary/interstitial brachytherapy (ICISBT), and interstitial brachytherapy (ISBT) with perineal approach] using dose-volume histograms using eight sizes of HR CTV (2 × 2 × 2 cm to 7 × 4 × 4 cm) and organs at risk model. Results In Conv ICBT, the doses covered 90% of the HR CTV [ D 90 (HR CTV)] decreased from 197% prescribed dose (PD) for the HR CTV size (2 × 2 × 2 cm) to 73% PD for 5 × 4 × 4 cm, whereas the other three modalities could achieve 100% PD for all HR CTV sizes. The minimum doses received by the maximally irradiated 2-cm 3 volumes for organs at risks of IGICBT demonstrated lower values than those of Conv ICBT for the HR CTV size of 4 × 3 × 3 cm or smaller. ICISBT demonstrated lower values than those of IGICBT for 4 × 3 × 3 cm or larger. ISBT demonstrated lowest values for 5 × 4 × 4 cm or larger. Conclusions HR CTV size of 4 × 3 × 3 cm seems to be a threshold volume in this simulation analysis, and IGICBT is a better choice for smaller HR CTV than the threshold volume. On larger HR CTV, ICISBT or ISBT is the better choice.

We analyzed clinical data to evaluate the effectiveness of image-guided high-dose-rate interstitial brachytherapy (HDR-ISBT) for pelvic recurrence of uterine cancer.Between 2003 and 2011, 56 patients were treated with HDR-ISBT with or without external beam radiotherapy (EBRT). The median followup time was 33 months (range, 1-109 months). Pre-ISBT treatments included radical hysterectomy for 35 patients (Group A), radical hysterectomy with postoperative radiotherapy for 8 patients (Group B), and radical radiotherapy for 13 patients (Group C). We initiated MRI-assisted CT-based planning for the last 49 patients. The median ISBT single fraction dose was 6 Gy. The median total doses were 30 and 54 Gy with and without EBRT (range, 30-50 Gy) for Group A, respectively and 48 Gy without EBRT for Groups B and C.The 3-year local control (LC) rates were 85%, 75%, and 46% for Groups A, B, and C, respectively (p = 0.017). The 3-year LC rates were 84%, 73%, and 33% for clinical target volume at the time of HDR-ISBT of10, 10-29, and ≥30 cc, respectively (p = 0.005). The 3-year LC results tended to be higher for patients whose D100 (clinical target volume) was equal or higher than 67.1 Gy (p = 0.098). A total of 13 late complications of Grades 3-5 occurred in 11 patients (20%).Our image-guided HDR-ISBT for pelvic recurrence of uterine cancer provided good treatment outcomes. The treatment results for patients who underwent radical surgery with or without postoperative radiotherapy are better than those for patients who underwent radical radiotherapy.

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 30Gy in 5 fractions with CyberKnife SBRT after 60Gy/30 fractions of previous radiotherapy. The median duration between reirradiation and CBOS onset was 5months (range, 0–69months). CBOS cases showed a median survival time of 5.5months compared to 22.8months 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.

Purpose To investigate the effectiveness of our novel MRI-assisted high-dose-rate interstitial brachytherapy for uterine cervical cancer. Methods and Materials Between June 2005 and June 2009, 29 previously untreated patients with cervical cancer were enrolled (2 T2b, 2 T3a, 19 T3b, and 6 T4 tumors). We implanted MRI-compatible plastic catheters using our unique ambulatory technique. The total treatment doses were 30–36 Gy (6 Gy per fraction) combined with external beam radiotherapy. Results The median D 90 (high-risk clinical target volume), D 2 cc (bladder), and D 2 cc (rectum) per fraction were 6.9, 5, and 4.6 Gy, respectively. The 3-year local control rates were 100%, 95%, and 83% for T2, T3, and T4 tumors, respectively. Grade 3 or 4 late complications occurred in 4 patients. Conclusions Our preliminary evaluation of image-based high-dose-rate interstitial brachytherapy showed favorable local treatment results with an acceptable complication rate.

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. 2013 Published by Elsevier Ireland Ltd. Radiotherapy and Oncology 107 (2013) 305–309

We investigated daily needle applicator displacement during high-dose-rate interstitial brachytherapy.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.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 (p0.0001), 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.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.

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

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.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.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 V40or= 8 cc than those with the rectal V408 cc (42% vs. 8%; p0.001), as well as for patients with rectal D5ccor= 27 Gy compared with those with rectal D5cc27 Gy (50% vs. 11%; p0.001). Dosimetric parameters of the urethra of 15 patients with late urinary toxicity were not significantly different from the 68 patients without toxicity.Rectal V408 cc and D5cc27 Gy may be dose-volume constraints in HDR-BT used as monotherapy for prostate cancer.