Simulation analysis of optimized brachytherapy for uterine cervical cancer: Can we select the best brachytherapy modality depending on tumor size?

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 (ConvICBT), 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 ConvICBT, the doses covered 90% of the HR CTV [D90(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 ConvICBT 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.

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.

Aftermath of 3/11: earthquakes and involuntary attentional orienting to sudden ambient sounds.

Due to the Great East Japan Earthquake on 11 March 2011 and the following long-term earthquake swarm, many people living in the earthquake-affected areas have developed mental stress, even though clinically-diagnosable symptoms may not be apparent. Concurrently, many unusual reports have emerged in which persons complain of abnormally increased sensitivity to sudden ambient sounds during their daily lives (e.g., the sound of the washing machine on spin cycle). By recording event-related potentials to various sudden ambient sounds from young adults living in the affected areas, we found that the level of earthquake-induced mental stress, as indexed by the hyperarousal symptoms of posttraumatic stress disorder, was positively related to the magnitude of P3a to sudden ambient sounds. These results reveal a strong relationship between mental stress and enhanced involuntary attentional orienting in a large majority of trauma-exposed people without diagnosable symptoms.

Differential regulation of amyloid precursor protein/presenilin 1 interaction during Aß40/42 [corrected] production detected using fusion constructs.

Beta amyloid peptides (Aß) play a key role in the pathogenesis of Alzheimer disease (AD). Presenilins (PS) function as the catalytic subunits of γ-secretase, the enzyme that releases Aß from ectodomain cleaved amyloid precursor protein (APP) by intramembrane proteolysis. Familial Alzheimer disease (FAD)-linked PSEN mutations alter APP processing in a manner that increases the relative abundance of longer Aß42 peptides to that of Aß40 peptides. The mechanisms by which Aß40 and Aß42 peptides are produced in a ratio of ten to one by wild type presenilin (PS) and by which Aß42 is overproduced by FAD-linked PS variants are not completely understood. We generated chimeras of the amyloid precursor protein C-terminal fragment (C99) and PS to address this issue. We found a chimeric protein where C99 is fused to the PS1 N-terminus undergoes in cis processing to produce Aß and that a fusion protein harboring FAD-linked PS1 mutations overproduced Aß42. To change the molecular interactions within the C99-PS1 fusion protein, we made sequential deletions of the junction between C99 and PS1. We found differential effects of deletion in C99-PS1 on Aß40 and 42 production. Deletion of the junction between APP CTF and PS1 in the fusion protein decreased Aß40, while it did not decrease Aß42 production in the presence or absence of FAD-linked PS1 mutation. These results are consistent with the idea that the APP/PS interaction is differentially regulated during Aß40 and 42 production.

Assessment of daily needle applicator displacement during high-dose-rate interstitial brachytherapy for prostate cancer using daily CT examinations.

To improve treatment conformity for prostate cancer, we investigated daily applicator displacement during high-dose-rate interstitial brachytherapy (HDR-ISBT). Thirty patients treated with HDR-ISBT as monotherapy were examined. All patients received a treatment dosage of 49 Gy per 7 fractions over 4 days. For dose administration, we examined 376 flexible applicators (1128 points) using our unique ambulatory implant technique. Using CT images with a 3-mm slice thickness, we calculated the relative coordinates of the titanium markers and the tips of the applicators. We calculated the distance between the center of gravity of the markers and the tips of the catheters, and compared the distances measured on the day of implantation and the second, third, and fourth treatment days. The mean displacement distance for all applicators was 4.3 ± 3.4 mm, 4.6 ± 4.1 mm, and 5.8 ± 4.5 mm at 21, 45, and 69 hours after initial planning CT. We used a 15-mm margin for needle displacement and only 2 points of 2 patients (16 mm and 18 mm at 69 hours, 2/1128 = 0.2%) exceeded this range. Almost patients (87%) showed the largest displacement within the first 21 hours. The relative doses that covered 100% of CTV (D100(CTV)) values compared with the initial treatment plan were reduced to 0.96 ± 0.08, 0.96 ± 0.08 and 0.94 ± 0.1 at 21, 45 and 69 hours. However, the relative D90(CTV) values kept acceptable levels (1.01 ± 0.02, 1.01 ± 0.03 and 1.01 ± 0.03). Cranial margin of 15 mm seems to be effective to keep D90(CTV) level if we do not do corrective action.

Interstitial brachytherapy using virtual planning and Doppler transrectal ultrasonography guidance for internal iliac lymph node metastasis.

To expand the indications for high-dose-rate interstitial brachytherapy (HDR-ISBT) for deep-seated pelvic tumors, we investigated the usefulness of Doppler transrectal ultrasonography (TRUS) guidance and virtual planning. The patient was a 36-year-old female. She had right internal iliac lymph node oligometastasis of vaginal cancer 12 months after radical radiotherapy. The tumor could not be found by gray-scale TRUS and physical examination. Virtual planning was performed using computed tomography with template and vaginal cylinder insertion. We uploaded the images to our treatment planning software and reconstructed the contours of the clinical target volume (CTV) and right internal iliac vessel. Virtual needle applicators were plotted using the template holes for virtual planning. At the time of implantation, Doppler TRUS was used to prevent vessel injury by needle applicators. Applicators were implanted in accordance with virtual planning and Doppler TRUS could detect the right iliac vessel. The percentage of CTV covered by the prescribed dose was 99.8%. The minimum dose received by the maximally irradiated 0.1-cc volume for the right internal iliac vessel was 95% prescribed dose. Complete response was achieved, however, radiological findings showed marginal recurrence at 15 months after HDR-ISBT. Post-radiation neuropathy occurred as a late complication four months after treatment; however, the pain was well controlled by medication. We consider that virtual planning and Doppler TRUS are effective methods in cases where it is difficult to detect the tumor by physical examination and gray-scale TRUS, thereby expanding the indications for ISBT.

Daily CT measurement of needle applicator displacement during multifractionated high-dose-rate interstitial brachytherapy for postoperative recurrent uterine cancer.

We investigated daily needle applicator displacement during multifractionated high-dose-rate interstitial brachytherapy (HDR-ISBT) for postoperative recurrent uterine cancer. Eight patients with postoperative recurrent uterine cancer received HDR-ISBT with or without external beam radiotherapy using our unique ambulatory technique. To analyze displacement, we obtained daily computed tomography (CT) images for 122 flexible needle applicators at 21, 45, 69, and 93 hours after implantation. Displacement was defined as the length between the center of gravity of titanium markers and the needle applicator tips along the daily CT axis. For cases in which displacement was not corrected, we also calculated the dose that covered 90% of the clinical target volume (D90(CTV)) using a dose-volume histogram (DVH). Median caudal needle applicator displacement at 21, 45, 69, and 93 hours was 3, 2, 4, and 5 mm, respectively. More than 15 mm displacement was observed for 2% (2 of 122) and 17% (10 of 60) of needle applicators at 21 and 93 hours, respectively. Cases in which dwell positions were not changed to correct the treatment plan, 2 of 8 patients showed more than 10% reduction in D90(CTV) values compared with the initial treatment plan. Correction of dwell positions of the treatment source improves treatment DVH for multifractionated HDR-ISBT.

[A retrospective study of advanced ovarian cancer in our ward].

OBJECTIVE: To evaluate the efficacy of primary treatment for ovarian cancer from overall survival and progression-free survival. PATIENTS AND METHODS: A total of 28 patients with epithelial ovarian cancer in stages III and IV who were primarily treated in our ward from 1993 were examined retrospectively. The Kaplan-Meier method and Harrington-Fleming test were carried out for the cumulative survival rate and analysis. RESULTS: There were significant differences in the progression-free survival rate depending on whether or not optimal debulking was possible through primary treatment (p = 0.0128) and whether the histological diagnosis was serous adenocarcinoma (p = 0.038). In the serous adenocarcinoma group, the periods of both overall survival and progression-free survival were longer in treatment with taxanes and platinum than by other regimens, but in the endometrioid adenocarcinoma group, the period of progression-free survival was very short. CONCLUSIONS: Optimal debulking through primary treatment is critical in advanced ovarian cancer. Therapy with taxanes and platinum is efficacious for serous adenocarcinoma. The chemo-sensitivity of endometrioid adenocarcinoma is high, but the chemotherapeutic effect is only temporary.