An assessment of interfractional uterine and cervical motion: Implications for radiotherapy target volume definition in gynaecological cancer

PURPOSE: To assess interfractional movement of the uterus and cervix in patients with gynaecological cancer to aid selection of the internal margin for radiotherapy target volumes. METHODS AND MATERIALS: Thirty-three patients with gynaecological cancer had an MRI scan performed on two consecutive days. The two sets of T2-weighted axial images were co-registered, and the uterus and cervix outlined on each scan. Points were identified on the anterior uterine body (Point U), posterior cervix (Point C) and upper vagina (Point V). The displacement of each point in the antero-posterior (AP), supero-inferior (SI) and lateral directions between the two scans was measured. The changes in point position and uterine body angle were correlated with bladder volume and rectal diameter. RESULTS: The mean difference (+/-1SD) in Point U position was 7mm (+/-9.0) in the AP direction, 7.1mm (+/-6.8) SI and 0.8mm (+/-1.3) laterally. Mean Point C displacement was 4.1mm (+/-4.4) SI, 2.7mm (+/-2.8) AP, 0.3 (+/-0.8) laterally, and Point V was 2.6mm (+/-3.0) AP and 0.3mm (+/-1.0) laterally. There was correlation for uterine SI movement in relation to bladder filling, and for cervical and vaginal AP movement in relation to rectal filling. CONCLUSION: Large movements of the uterus can occur, particularly in the superior-inferior and anterior-posterior directions, but cervical displacement is less marked. Rectal filling may affect cervical position, while bladder filling has more impact on uterine body position, highlighting the need for specific instructions on bladder and rectal filling for treatment. We propose an asymmetrical margin with CTV-PTV expansion of the uterus, cervix and upper vagina of 15mm AP, 15mm SI and 7mm laterally and expansion of the nodal regions and parametria by 7mm in all directions.     

Expression and role of PTV1 lncRNA in glioma cells progression

Objective The aim of this study was to investigate the expression of PTV1 lncRNA in gliomas and the mechanism of its interaction with miR-203a.Methods U87 and U251 cells were cultured stably and transfected with sh-PTV1 or ov-PTV1, respectively. The proliferative activity of U87 and U251 cells was detected and the transplanted tumor model nude mice were divided into U87 and U251 groups. U87-sh and u251-ov cells were injected into the armpit, then miR-203a mic and miR-203a inhibitors were administered to detect the changes in the expression of tumor-related proteins. Results The relative expression of PTV1 in gliomas was significantly higher than that in normal brain tissues, while in GBM it was significantly higher than that in low-grade gliomas. Knockdown of PTV1 significantly inhibited the proliferation of U87 cells, resulting in fewer cell clones; overexpression of rPTV1 significantly promoted the proliferation of U251 cells, resulting in more cell colonies. The dual Luciferase Reporter assay showed that SP2 was a potential target of miR-203a. When U87 cells were treated with a miR-203a mimic, the expression of SP2 decreased; and when U251 cells were treated with a miR-203a inhibitor, the expression of SP2 increased significantly. SP2 was overexpressed in u87-sh cells and the proliferation, migration, and invasion of u87-sh cells were significantly enhanced. U251-ov cells showed the opposite trend. Compared with the control group mice, the tumor volume in u87-sh group mice was significantly smaller and the positive rate of SP2 in tumor tissue was significantly lower. After administration of the miR-203a inhibitor, the tumor volume increased gradually and the positive rate of SP2 increased significantly, while u251-ov mice showed the opposite trend. Conclusion lncRNA PTV1 can be used as a molecule to interfere with miR-203a expression in order to downregulate SP2 and to promote the proliferation and invasion of glioma cells. lncRNA PTV1 may be a new biomarker and therapeutic target for glioma.     

Performance evaluation of field-in-field technique for tangential breast irradiation

Conventional hard or dynamic wedge systems are commonly applied to reduce the dose inhomogeneity associated with whole breast irradiation. We evaluated the dosimetric benefits of the field-in-field (FIF) technique by comparing it with the electronic compensator (EC), Varian enhanced dynamic wedge (EW) and conventional hard wedge (HW) techniques. Data were obtained from 12 patients who had undergone breast-conserving surgery (six left-sided and six right-sided). For these patients, the average breast planning target volume (PTV) was 447.4 cm(3) (range, 211.6-711.8 cm(3)). For the experiments, a 6 MV photon beam from a Varian 21 EX was used, the HW and EW angles were applied from 15 to 45 degrees, while 40-50% isodose values were chosen to achieve the best dose distribution for electronic compensation. In applying the FIF technique, we used two or three subfields for each portal. To evaluate the performance for each planning technique, we analysed a dose-volume histogram (DVH) for the PTV and organs-at-risk (OARs). To evaluate the effects of these techniques on dose inhomogeneity, we defined the PTV Dose Improvement (PDI) index, which was derived from a PTV volume between 97-103% of the differential DVHs. In addition, we compared the average monitor units (MUs) for each technique. The average PDI index with FIF is 76.4%, while the PDI indices for other treatments were 65.8, 41.8 and 50.9% for EC, EW and HW, respectively. This study demonstrated an improved performance using the FIF technique compared with the conventional HW/EW system, as well as a new modality for EC. We demonstrated that FIF is a very useful technique for improving PTV conformity, while protecting the OARs from breast tangential irradiation.     

Cholesteryl Ester Transfer Protein Inhibition for Preventing Cardiovascular Events: JACC Review Topic of the Week

Cholesteryl ester transfer protein (CETP) facilitates exchange of triglycerides and cholesteryl ester between high-density lipoprotein (HDL) and apolipoprotein B100–containing lipoproteins. Evidence from genetic studies that variants in the CETP gene were associated with higher blood HDL cholesterol, lower low-density lipoprotein cholesterol, and lower risk of coronary heart disease suggested that pharmacological inhibition of CETP may be beneficial. To date, 4 CETP inhibitors have entered phase 3 cardiovascular outcome trials. Torcetrapib was withdrawn due to unanticipated off-target effects that increased risk of death, and major trials of dalcetrapib and evacetrapib were terminated early for futility. In the 30,000-patient REVEAL (Randomized Evaluation of the Effects of Anacetrapib through Lipid Modification) trial, anacetrapib doubled HDL cholesterol, reduced non-HDL cholesterol by 17 mg/dl (0.44 mmol/l), and reduced major vascular events by 9% over 4 years, but anaceptrapib was found to accumulate in adipose tissue, and regulatory approval is not being sought. Therefore, despite considerable initial promise, CETP inhibition provides insufficient cardiovascular benefit for routine use.     

Efficient and Effective Personalization of PTV Margins During Radiation Therapy for Bladder Cancer

IntroductionThe magnitude of bladder filling variation during bladder cancer radiation therapy varies considerably between patients. Population-based approaches for planning target volume (PTV) margin calculation may be suboptimal for this disease site, and a strategy for personalizing PTV margins for each patient may be particularly beneficial. The purpose of this study was to identify the optimal number and sampling pattern of cone beam CT image data sets that are required when generating personalized PTV margins for whole bladder (WB) and partial bladder (PB) radiation therapy.Methods and MaterialsPersonalized PTV margins were generated for 24 bladder cancer patients (15 WB and 9 PB) using nine experimental strategies that varied in the number and pattern of images incorporated into the margin generation process. These PTVs were compared to the standard-of-care (SoC) PTV at our institution (15 daily fractions included) using PTV volume (cohort-based and individual patient ranking), superior and posterior expansion, and clinical target volume (CTV) coverage.ResultsFor WB CTV, strategies ES4 (first five fractions), ES7 (every other fraction), and ES8 (first 10 fractions), provided CTV coverage equivalent to, or better than the SoC (first 15 fractions). Of these three strategies, ES4 resulted in the smallest superior and posterior borders, the smallest volume and the lowest intrapatient volume ranking, all achieved with the smallest number of fractions. For the PB CTV, strategies ES4 (first five fractions), ES7 (every other fraction), ES8 (first 10 fractions), and ES9 (last 10 fractions), provided CTV coverage equivalent to, or better than SoC (first 15 fractions). There were no statistically significant differences in the superior and posterior borders between these strategies, but ES4 resulted in the smallest volume and the lowest intrapatient volume ranking, all achieved with the smallest number of fractions.ConclusionsThis study suggests that using contours from images taken during the first five daily fractions generated a personalized “patient-specific” PTV that provided CTV coverage equivalent to the 15-fraction SoC but decreased the irradiated volume, reduced delineation workload, and reduced the superior and posterior borders for WB. It is now the SoC for whole and PB radiation therapy at our institution.     

Earlier and sustained response with incidental use of cardiovascular drugs among patients with low- to medium-grade meningiomas treated with radiosurgery (SRS) or stereotactic radiotherapy (SRT)

Background and purpose

Beneficial outcome for cancer treated with radiotherapy (RT) and β-blockers has been reported. We hypothesize a potential combined impact of stereotactic RT with incidental use of cardiovascular drugs also in meningiomas.

Materials and methods

In 64 patients with 70 intracranial meningiomas (male/female = 17/53; median follow-up = 2 years) from a prospective database with sustained RT/cardiovascular drug therapy tumor response (progression, stable disease, regression) was evaluated at predefined follow-up intervals of 3, 12 and 24 months based on MR-imaging. For this retrospective cohort analysis stepwise univariate and multivariate analyses for group comparison were performed. Between groups analysis and stepwise uni- and multivariate analysis was performed.

Results

At one year follow-up there was a significant better tumor response for patients with antihypertensives use (p = 0.008) and radiosurgery (SRS) (p = 0.054), the difference between patients with and without antihypertensive medication remains significant in multivariate analysis. Two years after RT, only patients with β-blocker use had a significant better response to RT (p = 0.032). Additionally, for the use of β-blockers a trend toward significance for early tumor response at 3 months compared to the control group was observed (p(one tailed) = 0.059).

Conclusions

Our data suggest that concomitant antihypertensive medication (especially β-blockers) may lead to an earlier and sustained response in stereotactic irradiated low- to medium-grade intracranial meningiomas by affecting the β-adrenergic pathways.     

Different treatment planning protocols can lead to large differences in organ at risk sparing

Background and purposeDifferent planning protocols may define varying planning target volume (PTV) dose criteria. We investigated the hypothesis that this could result in differences in organ-at-risk (OAR) sparing.Material and methodsVolumetric modulated arc therapy plans were created for ten locally advanced head and neck cancer patients following PTV criteria specified by the RTOG, EORTC and institutional (VUmc) protocols. Resulting plans were evaluated on the basis of the homogeneity index, calculated for the boost/elective PTVs as HI_B/HI_E = 100% * (D2% − D98%)/D50% and mean dose to individual and composite salivary (comp_sal) and swallowing (comp_swal) OARs.ResultsRTOG plans were the most homogeneous, with mean HI_B of 8.2 ± 0.9%, compared to 9.5 ± 1.0%/11.6 ± 1.5% for the VUmc/EORTC plans. EORTC plans provided most OAR sparing, with comp_sal/comp_swal doses of 24.6 ± 7.7/22.9 ± 4.2 Gy, compared to 32.2 ± 9.7/29.9 ± 4.2 Gy and 28.4 ± 8.1/24.7 ± 5.3 Gy for RTOG and VUmc, respectively. EORTC provided 7.2/7.7 Gy mean dose reductions to the contra/ipsilateral parotid glands compared to RTOG.ConclusionsDifferent planning protocols resulted in different levels of PTV dose homogeneity. We observed differences of up to ⩾7 Gy in composite and individual mean OAR doses. This could influence rates of toxicity and should be taken into account when comparing clinical studies. A consensus should be reached between major trial groups on appropriate PTV parameters.     

应用锥形束CT对宫颈癌及子宫内膜癌术后放疗位置误差的研究

目的 通过对宫颈癌及子宫内膜癌术后放射治疗患者位置误差的分析,确定临床靶区（CTV）外扩计划靶区（PTV）边界值的大小。方法 选取26例宫颈癌及子宫内膜癌术后放疗患者通过千伏级锥形束CT（kV-CBCT）采集初次治疗前和以后每周的CT影像,与治疗计划采用的CT影像进行比对,记录各方向位置误差值并计算PTV外扩边界值M_PTV。 结果 宫颈癌及子宫内膜癌术后患者放疗时各方向均存在位置误差,患者在左右、头脚和前后方向误差分别为（0.21±3.23）、（0.55±3.51）和（0.08±2.76）mm,头脚方向的系统误差最大,左右方向次之、前后方向最小。各方向位置误差无明显差异。靶区在左右、头脚和前后方向依次需外扩5.44、7.26和5.68 mm。 结论 建议在进行宫颈癌及子宫内膜癌术后放疗时外扩PTV间距依次为左右方向5.5 mm、头脚方向7.5 mm、前后方向6 mm。