Tanja Skyttä

Improving the reproducibility of voluntary deep inspiration breath hold technique during adjuvant left-sided breast cancer radiotherapy

Abstract Background: Adjuvant radiotherapy (RT) of left-sided breast cancer (LSBC) with voluntary deep inspiration breath hold (vDIBH) technique reduces the cardiac dose. In this study, the effect of marker block position and the efficacy of breath hold level (BHL) correction based on lateral kV setup images are evaluated to improve the daily reproducibility. Material and methods: A total of 148 consecutive LSBC patients treated with vDIBH RT were included in this study. The real-time position management (RPM) marker block was placed on the abdominal wall in 63 patients (group A) and on the sternum in 85 patients (group S). Acquired 900 (group A) + 1040 (group S) orthogonal image pairs were retrospectively analyzed. The actual BHL was determined from the lateral kV images. The height of the BHL gating window in RPM was corrected if errors of the actual BHL exceeded 4 mm. Setup margins were calculated for the chest wall and for bony surrogates of the lymph node regions. Results: The sternal marker block reduced the random residual errors in the actual BHL (p < 0.05). The BHL correction was required for 26/63 patients in group A and for 26/85 patients in group S. Correction of the BHL window significantly reduced both the systematic and the random residual error in both groups. In patients with lymph node irradiation, the effect of both marker placement and BHL window correction was significant in the superior-inferior direction. Correction of the BHL reduced the mean cardiac dose by 0.5 Gy (p < 0.01) in group A and 0.6 Gy (p < 0.05) in group S. Conclusions: Reproducibility of the BHL can be improved by placing the marker block on the sternum and correcting the height of the BHL window based on lateral kV setup images. Acquisition of lateral kV images in the first 3 fractions and once a week during RT is recommended.

A new split arc VMAT technique for lymph node positive breast cancer

PURPOSE To investigate different volumetric modulated arc therapy (VMAT) field designs for lymph node positive breast cancer patients when compared to conventional static fields and standard VMAT designs. METHODS Nineteen breast cancer patients with lymph node involvement (eleven left and eight right sided) were retrospectively analyzed with different arc designs. Proposed split arc designs with total rotations of 2×190° and 2×240° were compared to conventional field in field (FinF) and previously published non-split arc techniques with the same amount of total rotations. RESULTS All VMAT plans were superior in dose conformity, when compared to the FinF plans. Split arc design decreased significantly ipsilateral lung dose and heart V5Gy for both left and right sided cases, when compared to non-split VMAT designs. For left sided cases no significant differences were seen in contralateral lung mean dose or V5Gy between different VMAT designs. For right sided cases the contralateral lung dose V5Gy was significantly higher in split VMAT group, when compared to non-split VMAT designs. The contralateral breast dose V5Gy increased significantly for split VMAT plans for both sides, when compared to non-split VMAT designs or FinF plans. CONCLUSIONS The proposed split VMAT technique was shown to be superior to previously published non-split VMAT and conventional FinF techniques significantly reducing dose to the ipsilateral lung and heart. However, this came with the expense of an increase in the dose to the contralateral breast and for right-sided cases to the contralateral lung.

Residual position errors of lymph node surrogates in breast cancer adjuvant radiotherapy: Comparison of two arm fixation devices and the effect of arm position correction

Residual position errors of the lymph node (LN) surrogates and humeral head (HH) were determined for 2 different arm fixation devices in radiotherapy (RT) of breast cancer: a standard wrist-hold (WH) and a house-made rod-hold (RH). The effect of arm position correction (APC) based on setup images was also investigated. A total of 113 consecutive patients with early-stage breast cancer with LN irradiation were retrospectively analyzed (53 and 60 using the WH and RH, respectively). Residual position errors of the LN surrogates (Th1-2 and clavicle) and the HH were investigated to compare the 2 fixation devices. The position errors and setup margins were determined before and after the APC to investigate the efficacy of the APC in the treatment situation. A threshold of 5mm was used for the residual errors of the clavicle and Th1-2 to perform the APC, and a threshold of 7mm was used for the HH. The setup margins were calculated with the van Herk formula. Irradiated volumes of the HH were determined from RT treatment plans. With the WH and the RH, setup margins up to 8.1 and 6.7mm should be used for the LN surrogates, and margins up to 4.6 and 3.6mm should be used to spare the HH, respectively, without the APC. After the APC, the margins of the LN surrogates were equal to or less than 7.5/6.0mm with the WH/RH, but margins up to 4.2/2.9mm were required for the HH. The APC was needed at least once with both the devices for approximately 60% of the patients. With the RH, irradiated volume of the HH was approximately 2 times more than with the WH, without any dose constraints. Use of the RH together with the APC resulted in minimal residual position errors and setup margins for all the investigated bony landmarks. Based on the obtained results, we prefer the house-made RH. However, more attention should be given to minimize the irradiation of the HH with the RH than with the WH.

Circulating levels of VEGFR-1 and VEGFR-2 in patients with metastatic melanoma treated with chemoimmunotherapy alone or combined with bevacizumab.

There are no identified biomarkers that could predict response to antiangiogenic or traditional chemoimmunotherapy in metastatic melanoma. We hypothesized that soluble angiogenic factor receptors might help us to identify patients responsive to treatment. A series of 48 patients with stage IV melanoma participating in two phase II clinical trials were included. The trials included treatment with carboplatin, vinorelbine, and subcutaneous interleukin-2 (n=22) or treatment with bevacizumab, dacarbazine, and low-dose interferon-&agr;2a (n=26).Serum samples were prospectively collected and soluble vascular endothelial growth factor receptor 1 (s-VEGFR-1) and 2 (s-VEGFR-2) were measured before starting the trial treatment and during response evaluation.There was a trend toward longer overall survival among patients with higher-than-median serum VEGFR-1 levels (21.3 months) compared with 12.3 months in patients with low pretreatment s-VEGFR-1 levels (P=0.146). Pretreatment s-VEGFR-2 levels did not correlate to survival. Serum VEGFR-2 levels decreased during therapy in 44% of the patients and increased in 56% of the patients. VEGFR-2 increased in 78% (14 of 18) of the patients who progressed during therapy (P=0.017). VEGFR-2 decrease was associated with clinical benefit in 65% of the patients (11 of 17) and with progression in only four patients (P=0.016).High pretreatment levels of s-VEGFR-1 are associated with improved prognosis among patients with metastatic melanoma independently on therapy, whereas increased VEGFR-2 levels during therapy are associated with disease progression. These markers might be useful in selecting patients responsive to antiangiogenic therapy.

Decreases in TGF-β1 and PDGF levels are associated with echocardiographic changes during adjuvant radiotherapy for breast cancer

BackgroundRadiation-induced heart disease is mainly caused by activation of the fibrotic process. Transforming growth factor-beta 1 (TGF-β1) and platelet-derived growth factor (PDGF) are pro-fibrotic mediators. The aim of our study was to evaluate the behavior of TGF-β1 and PDGF during adjuvant radiotherapy (RT) for breast cancer and the association of these cytokines with echocardiographic changes.MethodsOur study included 73 women with early-stage breast cancer or ductal carcinoma in situ (DCIS) receiving post-operative RT but not chemotherapy. TGF-β1 and PDGF levels in serum samples taken before and on the last day of RT were measured by an enzyme-linked immunosorbent assay. Echocardiography was also performed at same time points. Patients were grouped according to a ≥ 15% worsening in tricuspid annular plane systolic excursion (TAPSE) and pericardium calibrated integrated backscatter (cIBS).ResultsIn all patients, the median TGF-β1 decreased from 25.0 (IQR 21.1–30.3) ng/ml to 23.6 (IQR 19.6–26.8) ng/ml (p = 0.003), and the median PDGF decreased from 18.0 (IQR 13.7–22.7) ng/ml to 15.6 (IQR 12.7–19.5) ng/ml (p < 0.001). The baseline TGF-β1, 30.7 (IQR 26.0–35.9) ng/l vs. 23.4 (IQR 20.1–27.3) ng/l (p < 0.001), and PDGF, 21.5. (IQR 15.7–31.2) ng/l vs. 16.9. (IQR 13.0–21.2) ng/ml, were higher in patients with a ≥ 15% decrease in TAPSE than in patients with a < 15% decrease. In patients with a ≥ 15% decrease in TAPSE, the median TGF-β1 decreased to 24.7 (IQR 20.0–29.8) ng/ml (p < 0.001), and the median PDGF decreased to 16.7 (IQR 12.9–20.9) ng/ml (p < 0.001). The patients with a < 15% decrease had stable TGF-β1 (p = 0.104), but PDGF decreased to 15.1 (IQR 12.5–18.6), p = 0.005. The patients with a ≥ 15% increase in cIBS exhibited a decrease in TGF-β1 from 26.0 (IQR 21.7–29.7) to 22.5 (IQR 16.6.-26.7) ng/ml, p < 0.001, and a decrease in PDGF from 19.8 (IQR 14.6–25.9) to 15.7 (IQR 12.8–20.2) ng/ml, p < 0.001. In patients with a < 15% increase, TGF-β1 and PDGF did not change significantly, p = 0.149 and p = 0.053, respectively.ConclusionWe observed a decrease in TGF-β1 and PDGF levels during adjuvant RT for breast cancer. Echocardiographic changes, namely, in TAPSE and cIBS, were associated with a greater decrease in TGF-β1 and PDGF levels. Longer follow-up times will show whether these changes observed during RT translate into increased cardiovascular morbidity.

Dosimetric effects of anatomical deformations and positioning errors in VMAT breast radiotherapy

Abstract Aim Traditional radiotherapy treatment techniques of the breast are insensitive for deformations and swelling of the soft tissue. The purpose of this study was to evaluate the dose changes seen with tissue deformations using different image matching methods when VMAT technique was used, and compare these with tangential technique. Methods The study included 24 patients with breast or chest wall irradiations, nine of whom were bilateral. In addition to planar kV setup imaging, patients underwent weekly cone‐beam computed tomography (CBCT) imaging to evaluate soft tissue deformations. The effect of the deformations was evaluated on VMAT plans optimized with 5‐mm virtual bolus to create skin flash, and compared to standard tangential plans with 2.5 cm skin flash. Isocenter positioning using 2D imaging and CBCT were compared. Results With postural changes and soft tissue deformations, the target coverage decreased more in the VMAT plans than in the tangential plans. The planned V90% coverage was 98.3% and 99.0% in the tangential and VMAT plans, respectively. When tattoo‐based setup and online 2D match were used, the coverage decreased to 97.9% in tangential and 96.5% in VMAT plans (P < 0.001). With automatic CBCT‐based image match the respective coverages were 98.3% and 98.8%. In the cases of large soft tissue deformations, the replanning was needed for the VMAT plan, whereas the tangential plan still covered the whole target volume. Conclusions The skin flash created using an optimization bolus for VMAT plans was in most cases enough to take into account the soft tissue deformations seen in breast VMAT treatments. However, in some cases larger skin flash or replanning were needed. The use of 2D match decreased the target coverage for VMAT plans but not for FinF plans when compared to 3D match. The use of CBCT match is recommended when treating breast/chest wall patients with VMAT technique.

Associations between ECG changes and echocardiographic findings in patients with acute non-ST elevation myocardial infarction

BACKGROUND ST segment depression (STD) and T wave inversion (TWI) are typical electrocardiographic (ECG) findings in non-ST elevation myocardial infarction (NSTEMI). In ST elevation myocardial infarction, ST changes represent transmural ischemia. The pathophysiological mechanisms of the ECG changes in NSTEMI are unclear. PURPOSE We studied the associations between ECG and the echocardiographic findings in NSTEMI patients. METHODS Twenty patients with acute NSTEMI were recruited during their hospital stay. A comprehensive echocardiography study was performed. The findings were compared with blinded ECG analyses. RESULTS Nine (45%) patients had STD, and 16 (85%) patients had TWI. In multivariable analysis, STD was independently associated with a lower global early diastolic strain rate (β=-5.061, p=0.033). TWI was independently associated with lower circumferential strain (β=0.132, p=0.032). CONCLUSIONS The typical ECG changes in NSTEMI patients were associated with subtle echocardiographic changes. STD was related to changes in diastolic function, and TWI was associated with systolic deterioration.

Detection of early radiotherapy-induced changes in intrinsic myocardial contractility by ultrasound tissue characterization in patients with early-stage breast cancer

Increased cardiovascular morbidity and mortality are major late complications after radiotherapy (RT) in the thoracic region. Ultrasound tissue characterization (UTC) is a noninvasive method for the identification of myocardial changes. The aim of this prospective clinical trial was to assess whether the analysis of cyclic variation of integrated backscatter (CVIBS) can detect early RT‐induced myocardial alterations.

A novel arc geometry setting for pelvic radiotherapy with extensive nodal involvement

The aim of this study was to find optimal planning approach for large planning targets with complicated geometry requiring wide field openings. The study presents a novel approach for arc geometry design for pelvic targets with extensive nodal involvement. A total of 15 patients with anorectal carcinoma or vulvar cancer were selected retrospectively. For each patient, one seven-field IMRT plan and three VMAT plans were calculated: one with two 360° arcs with no limitations for the field size (VMATw); one with two asymmetrically field-size-restricted 360° arcs (VMATr); and the proposed novel approach which consisted of one 360° arc with the field size restricted to the central PTV, and another arc divided into two 180° arcs, restricting the field sizes with the focus on the lymph nodes. The techniques were compared in terms of PTV coverage (VPTV(95%)), dose maximum (D(max)), dose conformity index (CI), homogeneity index (HI), and organs at risk doses. The proposed novel approach with one full and two half arcs tended to have better PTV coverage (VPTV(95%)=97%±2%, compared to 95%±3%,95%±3%, and 97%±2% in VMATw, VMATr, and 7f-IMRT, respectively) and lower maxima (D(max)=107%±1%, compared to 110%±3%,110%±4%, and 110%±4% in VMATw, VMATr, and 7f-IMRT, respectively); and lower or equal organs at risk doses. The superiority of the proposed technique (CI=1.16±0.05,HI=9±2) was more pronounced compared with the VMATw plans (CI=1.41±0.10, paired t-test p<0.001;HI=12±2,p<0.001), but the proposed technique was slightly better also in comparison with the VMATr plans (CI=1.21±0.07,p<0.001;HI=11±4,p=0.015) and 7f-IMRT plans (CI=1.18±0.03,p=0.016;HI=10±2,p=0.215). Radiotherapy treatment planning for large and complicated treatment volumes benefits not only from restricting the field size but also from careful field design that considers PTV geometry. This optimizes multileaf collimator movements, leading to better dose conformity and homogeneity. PACS number(s): 87.53.Jw, 87.55.D, 87.56.jk.The aim of this study was to find optimal planning approach for large planning targets with complicated geometry requiring wide field openings. The study presents a novel approach for arc geometry design for pelvic targets with extensive nodal involvement. A total of 15 patients with anorectal carcinoma or vulvar cancer were selected retrospectively. For each patient, one seven‐field IMRT plan and three VMAT plans were calculated: one with two 360° arcs with no limitations for the field size (VMATw); one with two asymmetrically field‐size‐restricted 360° arcs (VMATr); and the proposed novel approach which consisted of one 360° arc with the field size restricted to the central PTV, and another arc divided into two 180° arcs, restricting the field sizes with the focus on the lymph nodes. The techniques were compared in terms of PTV coverage (VPTV(95%)), dose maximum (D(max)), dose conformity index (CI), homogeneity index (HI), and organs at risk doses. The proposed novel approach with one full and two half arcs tended to have better PTV coverage (VPTV(95%)=97%±2%, compared to 95%±3%,95%±3%, and 97%±2% in VMATw, VMATr, and 7f‐IMRT, respectively) and lower maxima (D(max)=107%±1%, compared to 110%±3%,110%±4%, and 110%±4% in VMATw, VMATr, and 7f‐IMRT, respectively); and lower or equal organs at risk doses. The superiority of the proposed technique (CI=1.16±0.05,HI=9±2) was more pronounced compared with the VMATw plans (CI=1.41±0.10, paired t‐test p<0.001;HI=12±2,p<0.001), but the proposed technique was slightly better also in comparison with the VMATr plans (CI=1.21±0.07,p<0.001;HI=11±4,p=0.015) and 7f‐IMRT plans (CI=1.18±0.03,p=0.016;HI=10±2,p=0.215). Radiotherapy treatment planning for large and complicated treatment volumes benefits not only from restricting the field size but also from careful field design that considers PTV geometry. This optimizes multileaf collimator movements, leading to better dose conformity and homogeneity. PACS number(s): 87.53.Jw, 87.55.D, 87.56.jk: