T. Shimbo

Preliminary results of MRI-assisted high-dose-rate interstitial brachytherapy for uterine cervical cancer

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 D90 (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.

Sivelestat sodium hydrate reduces radiation-induced lung injury in mice by inhibiting neutrophil elastase

The aim of this study was to investigate whether sivelestat, a neutrophil elastase (NE) inhibitor, mitigates radiation-induced lung injury in mice. C57BL/6J mice were administered a dose of 20 Gy to the bilateral whole lungs. Sivelestat was administered immediately before and 1 h after irradiation in group RE2, and immediately before and 1, 3 and 6 h after irradiation in group RE4. Group R received irradiation without sivelestat injection. Mice that did not receive sivelestat injection or irradiation were used as controls. NE activity was measured 24 and 48 h after irradiation, and the mice were sacrificed 24 h, 48 h and 15 weeks after irradiation for histopathological examination. In groups RE2 and RE4, NE activity was significantly suppressed until 48 h after irradiation compared to group R. The degree of lung damage in each group was scored during histopathological examination. Results showed that the scores of groups RE2 and RE4 were significantly lower compared to those of group R 15 weeks after irradiation. In conclusion, sivelestat reduced radiation‑induced lung injury in the mice by suppressing NE activity and excessive inflammatory reactions.

A multicenter phase II study of preoperative chemoradiotherapy with S-1 plus oxaliplatin for locally advanced rectal cancer (SHOGUN trial)

PURPOSE This study was designed to evaluate the safety and efficacy of adding oxaliplatin to preoperative chemoradiotherapy (CRT) with S-1 in patients with locally advanced rectal carcinoma (LARC). PATIENTS AND METHODS This was a multicenter phase II study in patients with histologically proven clinical stage T3 or T4 (any N, M0) LARC. Patients preoperatively received oral S-1 (80 mg/m(2)/day on days 1-5, 8-12, 22-27, and 29-33) and infusional oxaliplatin (60 mg/m(2) days on 1, 8, 22, and 29) plus radiotherapy (50.4 Gy), with a chemotherapy gap in the third week of radiotherapy. Pathological complete response (pCR) was the primary endpoint. Secondary endpoints included toxicity, compliance, R0 resection rate, and downstaging rate. RESULTS A total of 45 patients were enrolled at six centers in Japan. All 45 patients received CRT, and 44 underwent operation. A pCR was achieved in 12 (27.3%) of the 44 patients who underwent surgery. Near-total tumor regression was confirmed in 47.7%. There were no grade 4 adverse events, and 11.1% of the patients had grade 3 adverse events. R0 resection was achieved in 95.5% of the patients. CONCLUSION Preoperative CRT with S-1 plus oxaliplatin had a high pCR rate and a favorable toxicity profile.

Treatment results of image-guided high-dose-rate interstitial brachytherapy for pelvic recurrence of uterine cancer

PURPOSE We analyzed clinical data to evaluate the effectiveness of image-guided high-dose-rate interstitial brachytherapy (HDR-ISBT) for pelvic recurrence of uterine cancer. METHODS AND MATERIALS 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. RESULTS 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 of <10, 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%). CONCLUSIONS 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.

Role of vaginal pallor reaction in predicting late vaginal stenosis after high-dose-rate brachytherapy in treatment-naive patients with cervical cancer

Objective To assess actual rates of late vaginal stenosis and identify predisposing factors for complications among patients with previously untreated cervical cancer following high-dose-rate brachytherapy. Methods We performed longitudinal analyses of 57 patients using the modified Dische score at 6, 12, 18, 24, 36, and 60 months after treatment, which consisted of 15 interstitial brachytherapys and 42 conventional intracavitary brachytherapys, with a median follow-up time of 36 months (range, 6 to 144 months). Results More than half of the patients developed grade 1 (mild) vaginal stenosis within the first year of follow-up, and grade 2 (97.5%, moderate) to grade 3 (severe) stenosis gradually increased with time. Actual stenosis rates for grade 1, 2, and 3 were 97.5% (95% confidence interval [CI], 92.7 to 97.5), 60.7% (95% CI, 42.2 to 79.3), and 7.4% (95% CI, 0 to 18.4) at 3 years after treatment. Pallor reaction grade 2-3 at 6 months was only a statistically significant predisposing factor for grade 2-3 late vaginal stenosis 3 years or later with a hazard ratio of 3.48 (95% CI, 1.32 to 9.19; p=0.018) by a multivariate Cox proportional hazard model. Patients with grade 0-1 pallor reaction at 6 months showed a grade ≥2 vaginal stenosis rate of 53%, whereas the grade 2-3 pallor reaction group achieved a grade ≥2 vaginal stenosis rate at 3 years at 100% (p=0.001). Conclusion High-dose-rate brachytherapy was associated with high incidence of late vaginal stenosis. Pallor reaction grade 2-3 at 6 months was predictive of late grade 2-3 vaginal stenosis at 3 years after treatment. These findings should prove helpful for patient counseling and preventive intervention.

Three-dimensional image-based high-dose-rate interstitial brachytherapy for mobile tongue cancer

To investigate the influence of a 3D image-based treatment-planning method for high-dose-rate interstitial brachytherapy (HDR-ISBT) for mobile tongue cancer, we analyzed dose–volume histogram results for the clinical target volume (CTV) and the mandible. Between October 2010 and November 2011, one and four patients having T2 and T3 tumors, respectively, were treated with HDR-ISBT. Multiplane implantation using 9–15 treatment applicators was performed. Lugols iodine staining, metal markers, ultrasonography, and magnetic resonance imaging were used to identify the contours of the gross tumor volume (defined as the CTV). The results of the image-based treatment plan were compared with those of the conventional simulated plan on the basis of a reference point 5 mm from the applicator position. The mean D90(CTV) and V100(CTV) were 112% of the prescribed dose (PD) and 98.1%PD, respectively, for the image-based plan, and 113%PD and 97.2%PD, respectively, for the conventional plan. The median CTVref/Vref was 0.23 for the image-based plan and 0.16 for the conventional plan (P = 0.01). The mean D0.1 cm3 (mandible), D1 cm3 (mandible), and D2 cm3 (mandible) were 80.1%PD, 62.5%PD, and 55.7%PD, respectively, for the image-based plan, and 109.1%PD (P = 0.02), 82.4%PD (P = 0.005), and 74%PD (P = 0.004), respectively, for the conventional plan). Image-based treatment planning may achieve high-conformity radiotherapy for the CTV and decrease irradiated doses to the mandible.

Edema worsens target coverage in high-dose-rate interstitial brachytherapy of mobile tongue cancer: a report of two cases.

Purpose We report our study on two patients to highlight the risk of underdosage of the clinical target volume (CTV) due to edema during high-dose-rate interstitial brachytherapy (HDR-ISBT) of mobile tongue cancer. Material and methods To treat the lateral side of the CTV, flexible applicator tubes were implanted on the mouth floor. Two-dimensional planning was performed using X-ray images for Case 1, and three-dimensional (3D) planning was performed using computed tomography (CT) for Case 2. Prescribed doses for both cases were 54 Gy in nine fractions. Case reports Case 1 was treated for cancer of the right lateral border of the tongue in 2005. Tongue edema occurred after implantation, and part of the lateral border of the tongue protruded between the applicator tubes. Acute mucosal reaction abated in the protruded area earlier than in the other parts of the CTV. In this case, the tumor recurred in this area 5 months after the treatment. Case 2 was treated for cancer of the left lateral border of the tongue. Because tongue edema occurred in this case also, plastic splints were inserted between the applicator tubes to push the edematous region into the irradiated area. The mucosal surface of the CTV was covered by the 70% isodose, and 100% isodose line for before and after splint insertion. Local control of the tumor was achieved 4 years after treatment. Discussion and conclusions To ensure sufficient target coverage, 3D image-based planning using CT should be performed, followed by re-planning using repeated CT as needed. Also, the development of devices to prevent protrusion of the edematous tissue outside the target area will help to ensure the full dosing of CTV.

Clinical implications of preoperative chemoradiotherapy prior to laparoscopic surgery for locally advanced low rectal cancer

The present study aimed to evaluate whether preoperative chemoradiotherapy (CRT) has any adverse effects on laparoscopic surgery (LS) for locally advanced low rectal cancer (LARC). The study was performed at the Osaka Medical College Hospital, and included patients who were operated on between July 2006 and December 2013. The short-term outcomes in 156 patients who underwent surgery for LARC following CRT were evaluated, of whom 152 underwent LS. Among the patients who were followed for >40 months, 77 patients (the CRT group) were compared with 39 patients who underwent LS without CRT (the surgery-alone group) for long-term outcomes. The total number of patients who received sphincter-preserving surgery was 74%. No positive longitudinal resection margins were identified, and only 1.3% had identifiable positive circumferential resection margins. The complication rate was 14%, and no serious complications occurred. There were no significant differences between the CRT and the surgery-alone groups in terms of the 5-year relapse-free survival rate (70.1 vs. 61.5%; P=0.81) or the 5-year overall survival rate (88.3 vs. 69.2%; P=0.06). However, the 5-year local recurrence-free survival rate was significantly improved in the CRT group patients (96.1 vs. 79.5%; P=0.009). In conclusion, our results have demonstrated that LS with preoperative CRT appears to be feasible and safe, and may have beneficial effects on local recurrence.

EP-1969: High-dose-rate image-guided interstitial brachytherapy for recurrent cervical adenocarcinoma

Results: Total doses from 3 fractions for the D5 v median 48.7Gy (range 31.4 76.6Gy), D2 v median 64.0Gy (range: 43.2 112Gy) and RV median dose 16.3Gy (range: 11.6 – 25.3Gy) The RV point exhibited a weak correlation with D2 v (r=0.56; p=0.0001) and D5 v (r = 0.55; p=0.0001) respectively. A moderate correlation was observed between the HRCTV volume and the D2 v (r = 0.69; p=0.0001), the HRCTV volume and D5 v (r = 0.73; p=0.0001) and a weak correlation with the HRCTV volume and the RV Point (r=0.57; p=0.0001). The slope correlated with D2 v (r= -0.96; p=0.0001) and D5 v (r=0.87; p=0.0001) and a weak correlation with the RV point (r=0.52; p=0.0002). No correlation was found between the HRCTV D90 and the D2v (r=-0.20; p=0.1826), the D5v (r=0.24; p=0.1082), or the RV Point (r=0.02; p=0.8431).

PO-0964: High-dose-rate interstitial brachytherapy as monotherapy for locally limited mobile tongue cancer

Material and Methods: We investigated 29 locally limited mobile tongue cancer treated by HDR-ISBT as monotherapy at National Hospital Organization Osaka National Hospital between February 2001 and August 2012. The median age of the patients was 60 years (range: 34–84 years). All patients had histologically confirmed squamous cell carcinoma. According to the UICC classification of 2007, 3 T1, 18 T2 and 8 T3 were classified, respectively. The median tumor thickness of the patients was 10 mm (range: 2–45 mm). Ten (34%) medically poor risk patients (more than 80 years of age or severe intercurrent disease) were included. One patient had previous irradiation history. All but one patients received 54 Gy in 9 fractions. The other patient reduced his treatment doses (48 Gy in 8 fractions) because of previous irradiation history. We used three-dimensional planning for later 7 patients and delivered the prescribed doses to CTV (clinical target volume). Gross tumor volume (GTV) was defined with metal markers positions, applicator positions, intraoral ultrasonography and CT image. The GTV was equal to the CTV.