Experimental iodine-125 seed irradiation of intracerebral brain tumors in nude mice

<p>Abstract</p> <p>Background</p> <p>High-dose radiotherapy is standard treatment for patients with brain cancer. However, in preclinical research external beam radiotherapy is limited to heterotopic murine models– high-dose radiotherapy to the murine head is fatal due to radiation toxicity. Therefore, we developed a stereotactic brachytherapy mouse model for high-dose focal irradiation of experimental intracerebral (orthotopic) brain tumors.</p> <p>Methods</p> <p>Twenty-one nude mice received a hollow guide-screw implanted in the skull. After three weeks, 5 × 10⁵U251-NG2 human glioblastoma cells were injected. Five days later, a 2 mCi iodine-125 brachytherapy seed was inserted through the guide-screw in 11 randomly selected mice; 10 mice received a sham seed. Mice were euthanized when severe neurological or physical symptoms occurred. The cumulative irradiation dose 5 mm below the active iodine-125 seeds was 23.0 Gy after 13 weeks (BED_tumor= 30.6 Gy).</p> <p>Results</p> <p>In the sham group, 9/10 animals (90%) showed signs of lethal tumor progression within 6 weeks. In the experimental group, 2/11 mice (18%) died of tumor progression within 13 weeks. Acute side effects in terms of weight loss or neurological symptoms were not observed in the irradiated animals.</p> <p>Conclusion</p> <p>The intracerebral implantation of an iodine-125 brachytherapy seed through a stereotactic guide-screw in the skull of mice with implanted brain tumors resulted in a significantly prolonged survival, caused by high-dose irradiation of the brain tumor that is biologically comparable to high-dose fractionated radiotherapy– without fatal irradiation toxicity. This is an excellent mouse model for testing orthotopic brain tumor therapies in combination with radiation therapy.</p

Potential benefits of the use of sympathomimetics for asthmatic disease, on semen quality in men of subfertile couples

Research question: Is there an association between the use of sympathomimetics for asthmatic disease and semen quality in humans? Design: Between 2007 and 2012 a prospective cohort study was conducted among couples visiting the preconception counselling clinic at a tertiary hospital in the Netherlands. The study included 882 men of subfertile couples and information on medication use was obtained from self-administered questionnaires. Moreover, data on semen parameters were retrieved from medical records. Results: The study population of men revealed a mean (± SD) age of 34 ± 4 years with a mean body mass index (BMI) of 26.1 ± 2.3 kg/m2, and sympathomimetic use was reported by 3.6%. The use of sympathomimetics was positively associated with a 10% higher sperm motility (beta 10.265; 95% confidence interval [CI] 3.258–17.272) after adjustment for smoking, alcohol use, age, geographic background, BMI, folic acid supplement use, the four astronomical seasons and asthma/bronchitis. Subgroup analysis between men with total motile sperm count (TMSC) < or ≥10 million showed that this association remained (P ≤ 0.001) after adjustment for these confounders. After adjustment for confounders the sperm concentration was also positively associated with the use of sympathomimetics, but only in men with TMSC ≥10 million (beta 0.300; 95% CI 0.032–0.568). Conclusions: These preliminary data show the potential benefits of the use of sympathomimetics to improve sperm motility in men of subfertile couples, which needs further investigation

Accelerated high-dose radiotherapy alone or combined with either concomitant or sequential chemotherapy; treatments of choice in patients with Non-Small Cell Lung Cancer

<p>Abstract</p> <p>Background</p> <p>Results of high-dose chemo-radiotherapy (CRT), using the treatment schedules of EORTC study 08972/22973 or radiotherapy (RT) alone were analyzed among all patients (pts) with Non Small Cell Lung Cancer (NSCLC) treated with curative intent in our department from 1995–2004.</p> <p>Material</p> <p>Included are 131 pts with medically inoperable or with irresectable NSCLC (TNM stage I:15 pts, IIB:15 pts, IIIA:57 pts, IIIB:43 pts, X:1 pt).</p> <p>Treatment</p> <p>Group I: Concomitant CRT: 66 Gy/2.75 Gy/24 fractions (fx)/33 days combined with daily administration of cisplatin 6 mg/m²: 56 pts (standard).</p> <p>Group II: Sequential CRT: two courses of a 21-day schedule of chemotherapy (gemcitabin 1250 mg/m²d1, cisplatin 75 mg/m2 d2) followed by 66 Gy/2.75 Gy/24 fx/33 days without daily cisplatin: 26 pts.</p> <p>Group III: RT: 66 Gy/2.75 Gy/24 fx/33 days or 60 Gy/3 Gy/20 fx/26 days: 49 pts.</p> <p>Results</p> <p>The 1, 2, and 5 year actuarial overall survival (OS) were 46%, 24%, and 15%, respectively.</p> <p>At multivariate analysis the only factor with a significantly positive influence on OS was treatment with chemo-radiation (P = 0.024) (1-, 2-, and 5-yr OS 56%, 30% and 22% respectively). The incidence of local recurrence was 36%, the incidence of distant metastases 46%.</p> <p>Late complications grade 3 were seen in 21 pts and grade 4 in 4 patients. One patient had a lethal complication (oesophageal). For 32 patients insufficient data were available to assess late complications.</p> <p>Conclusion</p> <p>In this study we were able to reproduce the results of EORTC trial 08972/22973 in a non-selected patient population outside of the setting of a randomised trial. Radiotherapy (66 Gy/24 fx/33 days) combined with either concomitant daily low dose cisplatin or with two neo-adjuvant courses of gemcitabin and cisplatin are effective treatments for patients with locally advanced Non-Small Cell Lung Cancer. The concomitant schedule is also suitable for elderly people with co-morbidity.</p

Dose warping uncertainties for the accumulated rectal wall dose in cervical cancer brachytherapy

Purpose: Structure-based deformable image registration (DIR) can be used to calculate accumulated dose volume histogram parameters for cervical cancer brachytherapy (BT). The purpose of this study is to investigate dose warping uncertainties for the accumulated dose to the 2 cm3 receiving the highest dose (D2cm3 ) in the rectal wall, using a physically realistic model (PRM) describing rectal wall deformation. Methods and materials: For 10 patients, treated with MRI-guided pulsed dose rate BT (two times 24 × 0.75 Gy, given in two applications BT1 and BT2), the planning images were registered with structure-based DIR. The resulting transformation vectors were used to accumulate the total rectum dose from BT. To investigate the dose warping uncertainty, a PRM describing rectal deformation was used. For point pairs on rectumBT1 and rectumBT2 that were at the same location according to the PRM, the dose for BT1 and BT2 was added (DPRM) and compared to the DIR-accumulated dose (DDIR) in the BT2 point. The remaining distance after DIR between corresponding point pairs, defined as the residual distance, was calculated. Results: For points within the D2cm3 volume, more than 75% was part of the D2cm3 volume according to both PRM and DIR. The absolute dose difference was <7.3 GyEQD2, and the median (95th percentile) of the residual distance was 8.7 (22) mm. Conclusions: DIR corresponded with the PRM for on average 75% of the D2cm3 volume. Local absolute dose differences and residual distances were large. Care should therefore be taken with DIR for dose-warping purposes in BT

Role of deformable image registration for delivered dose accumulation of adaptive external beam radiation therapy and brachytherapy in cervical cancer

Purpose: Deformable image registration (DIR) can be used to accumulate the absorbed dose distribution of daily image-guided adaptive external beam radiation treatment (EBRT) and brachytherapy (BT). Since dose-volume parameter addition assumes a uniform delivered EBRT dose around the planned BT boost, the added value of DIR over direct addition was investigated for dose accumulation in bladder and rectum. Material and methods: For 10 patients (EBRT 46/46.2 Gy EQD2 , EBRT + BT: D 90 85-90 Gy EQD2 , in equivalent dose in 2 Gy fractions), the actually delivered dose from adaptive volumetric-modulated arc therapy (VMAT)/intensity-modulated radiotherapy (IMRT) EBRT was calculated using the daily anatomy from the cone-beam computed tomography (CBCT) scans acquired prior to irradiation. The CBCT of the first EBRT fraction and the BT planning MRI were registered using DIR. The cumulative dose to the 2 cm 3 with the highest dose (D 2cm 3) from EBRT and BT to the bladder and rectum was calculated and compared to direct addition assuming a uniform EBRT dose (UD). Results: Differences (DIR-UD) in the total EBRT + BT dose ranged between –0.2-3.9 Gy EQD2 (bladder) and –1.0-3.7 Gy EQD2 (rectum). The total EBRT + BT dose calculated with DIR was at most 104% of the dose calculated with the UD method. Conclusions: Differences between UD and DIR were small (< 3.9 Gy EQD2 ). The dose delivered with adaptive VMAT/IMRT EBRT to bladder and rectum near the planned BT boost can be considered uniform for the evaluation of bladder/rectum D 2cm 3

SU‐E‐T‐326: Repeated CT‐Scans in Pulsed Doserate Prostate Brachytherapy: Assessment of Deviations from the Treatment Plan

Purpose: Estimation of deviations between planned and delivered dose in Pulsed Doserate (PDR) brachytherapy for prostate cancer. Methods: A boost of 28.8 Gy is given with PDR brachytherapy in addition to 46 Gy delivered with External Beam RT. Brachytherapy is given in 24 pulses of 120 cGy, with an interpulse period time of 2.0 hours, resulting in a treatment time of over 46 hours. For 31 patients, additional CT‐scans were made apart from the Treatment Planning CT, i.e., one at 24 hours after start of PDR treatment and one shortly before finishing PDR treatment. On the second and third CT, the brachytherapy catheters were newly reconstructed and the treating physician delineated the PTV and organs at risk. Dwell positions and dwell times as used for the original Treatment Plan were imported into the newly reconstructed catheters and the dose distribution was recalculated. Plan comparison parameters were prostate V100 and D90 and rectum and bladder D2cc. Results: Averaged over 3 CT scans and all patients, the prostate V100 decreased 1.2% and D90 decreased 2.7%. For rectum, D2cc was within the tolerance dose (96 cGy/pulse) for all patients on the planning CT, but exceeded the tolerance dose on scan #2 in 7/31 patients with maximally 46% and in scan #3 in 5/25 patients with maximally 29%. Also for bladder D2cc was within the tolerance dose (120 cGy/pulse) for all patients on the planning CT. Here, the tolerance dose was exceeded on scan #2 in 2/31 patients with maximally 14% and in scan #3 in 3/25 patients with maximally 28%. Conclusions: In PDR prostate brachytherapy the relatively long treatment time has no clinically relevant deteriorating effect on the dosimetric quality of the treatment. PTV dose hardly deviates from planned dose, while OAR tolerance doses are rarely exceeded and only in small volumes. © 2012, American Association of Physicists in Medicine. All rights reserved

Postoperative single-dose interstitial high-dose-rate brachytherapy in therapy-resistant keloids

Patients with keloids complain of the cosmetic aspect, pain, and pruritus. Many different therapies are being used for keloids. The aim of this study was to evaluate the recurrence rate and outcome after resection followed by a single-dose brachytherapy. Patients treated by resection of the keloid plus a single dose of 13 Gy high-dose-rate brachytherapy were evaluated at least 1 year after treatment. Clinical response and cosmesis were assessed by a plastic surgeon and by the patients using the Patient and Observer Scar Assessment Scale. Only 24 of the 61 invited patients responded to participate with the study; 29 keloids were evaluated. The recurrence rate was 24.1% after a median followup of 53 months (19-95 months). Patients scored on average 24.3 for their total Patient and Observer Scar Assessment Scale score (range 6-52), whereas the observer scored on average 14.6 (range 6-42). This treatment has a higher recurrence rate than that reported in most other studies. This may be explained by differences in recurrence definition, differences in followup time among studies, and selection bias because of not contributing to the study. The cosmetic outcome for evaluated patients is relatively good. This treatment policy has the advantage that patients are treated in a single da

A comparison of inverse optimization algorithms for HDR/PDR prostate brachytherapy treatment planning

PURPOSE: Graphical optimization (GrO) is a common method for high-dose-rate/pulsed-dose-rate (PDR) prostate brachytherapy treatment planning. New methods performing inverse optimization of the dose distribution have been developed over the past years. The purpose is to compare GrO and two established inverse methods, inverse planning simulated annealing (IPSA) and hybrid inverse treatment planning and optimization (HIPO), and one new method, enhanced geometric optimization-interactive inverse planning (EGO-IIP), in terms of speed and dose volume histogram (DVH) parameters. METHODS AND MATERIALS: For 26 prostate cancer patients treated with a PDR brachytherapy boost, an experienced treatment planner optimized the dose distributions using four different methods: GrO, IPSA, HIPO, and EGO-IIP. Relevant DVH parameters (prostate-V-100%, D-90%, V-150%; urethra-D-0.1cm3 and D-1.0cm3; rectum-D-0.1cm3 and D-2.0cm3; bladder-D-2.0cm3) were evaluated and their compliance to the constraints. Treatment planning time was also recorded. RESULTS: All inverse methods resulted in shorter planning time (mean, 4-6.7 min), as compared with GrO (mean, 7.6 min). In terms of DVH parameters, none of the inverse methods outperformed the others. However, all inverse methods improved on compliance to the planning constraints as compared with GrO. On average, EGO-IIP and GrO resulted in highest D-90%, and the IPSA plans resulted in lowest bladder D-2.0cm3 and urethra D-1.0cm3. CONCLUSIONS: Inverse planning methods decrease planning time as compared with GrO for PDR/high-dose-rate prostate brachytherapy. DVH parameters are comparable for all methods. (C) 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserve