Applicator reconstruction for HDR cervix treatment planning using images from 0.35 T open MR scanner

Background and purposes

Magnetic resonance (MR) imaging is widely recognised as the modality of choice for imaging soft tissue such as the target volume and critical structures relevant to high dose rate (HDR) brachytherapy of the cervix. This work sets out to assess some of the issues faced when introducing this technique clinically compared to the more widely used computed tomography (CT). MR can be used either as the sole imaging modality, or in conjunction with CT.

Materials and methods

Distortion of the images produced by the MR scanner was assessed with a geometrical phantom. Distortion local to the titanium applicators, introduced by the susceptibility of the applicators themselves, was also measured. The technique used to reconstruct applicators is briefly described. An inter-operator study was performed to assess the variability of applicator reconstruction between operators when MR images are used alone to reconstruct the applicators.

Results

A 14-cm cube within which distortion was less than 2 mm at all points was identified. The inter-operator study showed some variability in applicator reconstruction with both MR and CT (median MR/CT 1.3 mm/0.9 mm, range 0-3.6 mm/0-3.3 mm). Inter-operator variation in planning target volume (PTV) V100% and PTV D90% for MR/CT was 6.1%/3.0% and 7.4%/6.3%, respectively, and D_2cc OAR doses varied by up to 1.0 Gy between operators for both MR and CT.

Conclusions

In this study distortion was minimal within a defined volume and inter-observer errors were comparable on MR and CT when used to define applicators and when applied to dose-volume histograms (DVHs). However this does not assure the technique is appropriate with other scanners and applicator sets without further commissioning.     

Direct reconstruction of the Vienna applicator on MR images

Purpose

To introduce and test a direct reconstruction concept for intracavitary tandem ring applicators in MR image-based brachytherapy treatment planning.

Materials and methods

Optical measurements of transparent ring-phantoms provided the geometric relation between source path and the Vienna ring applicator as visible on MRI. For the manual direct reconstruction method (PLATO), the geometry plotted on a transparency was placed on the screen and rotated to fit with visible ring holes. With the software-integrated reconstruction method (OncentraGYN), the applicator geometry was directly used when placing the visible parts of the applicator in the 3D dataset. Clinical feasibility was tested in 10 clinical insertions. Reconstruction and dose calculation were performed independently on two treatment planning systems (PLATO and OncentraGYN) using MRI alone. DVH parameters for targets and organs at risk were analysed and compared to the clinically used radiograph/MRI registration-based method.

Results

The direct reconstruction concept for both methods was feasible and reduced treatment planning time. Evaluated DVH parameters for plans using direct reconstruction methods differed from clinically used plans (traditional reconstruction) in mean differences ?0.2 Gy for plans with 7 Gy prescribed dose.

Conclusion

If the relation between applicator shape visible on MRI and the source path is defined once, the reconstruction process can be performed by directly placing the applicator in the MRI dataset.     

Applicator reconstruction and applicator shifts in 3D MR-based PDR brachytherapy of cervical cancer

Purpose

To evaluate the methods of applicator reconstruction in 3D MR-based planning for brachytherapy of cervical cancer, and to investigate applicator shifts and changes in DVH parameters during PDR treatment.

Methods

For each application MR scans with applicator in situ were made: three T2-weighted (4.5 mm slices) Turbo Spin Echo (TSE) scans and a balanced Steady State Free Precession scan (1.5 mm). Three observers tested two applicator reconstruction methods: (A) directly on the bSSFP scan and (B) on a resampled combination of the three T2-weighted scans. For 10 patients MR imaging was repeated on the second day of each PDR fraction to determine applicator shifts and changes in DVH parameters.

Results

For both applicator reconstruction methods the interobserver variation for the DVH parameters was comparable (average <1.5% in dose). Differences between the two methods were larger (up to 6.4% for target) and were related to position differences during MR scanning.The average applicator shift relative to the pelvic structures was 5-6 mm into the ventral direction and 3-4 mm cranially. For a single PDR fraction, the average D90 (HR-CTV) on ‘day 2’ was 0.2 (SD 2.0) Gy lower than that for day 1. The average increase in D_2cc (bladder) was 1.0 (SD 3.0) Gy_αβ3 for a single PDR fraction. If the effect of both fractions was combined, for 1 patient a total decrease of D90 of 7 Gy_αβ10 was found, whereas for another patient the total increase in bladder dose was 12 Gy_αβ3.

Conclusions

Applicator reconstruction on MR data is feasible. In the overall accuracy during PDR brachytherapy the reconstruction uncertainty is of minor importance. Applicator and/or organ movement during the course of the PDR fraction produce larger uncertainties.     

后装施源器Offset值验证研究

目的 研究后装治疗中多种施源器的Offset值。方法 选取插植钢针(Part#083.062)、插植塑料圆针(Part#189.608)、插植塑料尖针(Part#189.601)、多通道施源器软管(Part#110.800)、塑料宫腔管(Part#189.745)、金属宫腔管(Part#110.437)施源器。根据源在荧光胶片放射性成像,确定施源器顶端驻留点位置以及到施源器顶端的距离。在施源器顶端驻留点位置贴铅珠,将施源器置入盆腔体模中进行CT扫描。然后在计划系统中重建施源器,通过调整Offset值使铅珠与施源器顶端驻留点对准,从而得到施源器Offset值。塑料材质施源器由于密度与人体组织接近,施源器顶端难以准确重建,因此利用挡块或者假源重建施源器,得到塑料材质施源器Offset值。根据验证结果分析比较不同施源器Offset值差异。结果 不同施源器Offset值存在较大差异,其中插植钢针为-11.4 mm,插植塑料圆针为-4.1 mm,插植塑料尖针为-3.5 mm,多通道施源器软管为0 mm或-5.0 mm,塑料宫腔管为-6.5 mm,金属宫腔管为-7.5 mm。结论 为了适应精确放疗的发展趋势,有必要对后装中施源器Offset值进行测量验证。     

后装施源器Offset值验证研究

目的 研究后装治疗中多种施源器的Offset值。方法 选取插植钢针(Part#083.062)、插植塑料圆针(Part#189.608)、插植塑料尖针(Part#189.601)、多通道施源器软管(Part#110.800)、塑料宫腔管(Part#189.745)、金属宫腔管(Part#110.437)施源器。根据源在荧光胶片放射性成像,确定施源器顶端驻留点位置以及到施源器顶端的距离。在施源器顶端驻留点位置贴铅珠,将施源器置入盆腔体模中进行CT扫描。然后在计划系统中重建施源器,通过调整Offset值使铅珠与施源器顶端驻留点对准,从而得到施源器Offset值。塑料材质施源器由于密度与人体组织接近,施源器顶端难以准确重建,因此利用挡块或者假源重建施源器,得到塑料材质施源器Offset值。根据验证结果分析比较不同施源器Offset值差异。结果 不同施源器Offset值存在较大差异,其中插植钢针为-11.4 mm,插植塑料圆针为-4.1 mm,插植塑料尖针为-3.5 mm,多通道施源器软管为0 mm或-5.0 mm,塑料宫腔管为-6.5 mm,金属宫腔管为-7.5 mm。结论 为了适应精确放疗的发展趋势,有必要对后装中施源器Offset值进行测量验证。     

Identifying afterloading PDR and HDR brachytherapy errors using real-time fiber-coupled Al2O3:C dosimetry and a novel statistical error decision criterion

Background and purpose

The feasibility of a real-time in vivo dosimeter to detect errors has previously been demonstrated. The purpose of this study was to: (1) quantify the sensitivity of the dosimeter to detect imposed treatment errors under well controlled and clinically relevant experimental conditions, and (2) test a new statistical error decision concept based on full uncertainty analysis.

Materials and methods

Phantom studies of two gynecological cancer PDR and one prostate cancer HDR patient treatment plans were performed using tandem ring applicators or interstitial needles. Imposed treatment errors, including interchanged pairs of afterloader guide tubes and 2-20 mm source displacements, were monitored using a real-time fiber-coupled carbon doped aluminum oxide (Al₂O₃:C) crystal dosimeter that was positioned in the reconstructed tumor region. The error detection capacity was evaluated at three dose levels: dwell position, source channel, and fraction. The error criterion incorporated the correlated source position uncertainties and other sources of uncertainty, and it was applied both for the specific phantom patient plans and for a general case (source-detector distance 5-90 mm and position uncertainty 1-4 mm).

Results

Out of 20 interchanged guide tube errors, time-resolved analysis identified 17 while fraction level analysis identified two. Channel and fraction level comparisons could leave 10 mm dosimeter displacement errors unidentified. Dwell position dose rate comparisons correctly identified displacements ?5 mm.

Conclusion

This phantom study demonstrates that Al₂O₃:C real-time dosimetry can identify applicator displacements ?5 mm and interchanged guide tube errors during PDR and HDR brachytherapy. The study demonstrates the shortcoming of a constant error criterion and the advantage of a statistical error criterion.     

Linac-based isocentric electron–photon treatment of radically operated breast carcinoma with enhanced dose uniformity in the field gap area

Background and purpose

Isocentric treatment technique is a standard method in photon radiotherapy with the primary advantage of requiring only a single patient set-up procedure for multiple fields. However, in electron treatments the size of the standard applicators does not generally allow to use an isocentric treatment technique. In this work we have modified and dosimetrically tested electron applicators for isocentric treatments in combination with photons. An isocentric treatment technique with photons and electrons for postmastectomy radiation therapy (PMRT) has been developed with special emphasis on improving the dose uniformity in the field gap area.

Materials and methods

Standard electron applicators of two Varian Clinac 2100CD linear accelerators were shortened by 10 cm allowing isocentric treatments of 90 cm < SSD < 100 cm in electron fields. Shortened applicators were commissioned and configured for the electron calculation algorithm of the treatment planning system. The field arrangement of PMRT was modified by combining three photon field segments with different gaps and overlaps with the electron field to improve dose uniformity. The developed technique and two other methods for PMRT were compared with each other in the group of 20 patients.

Results

Depth dose characteristics of the shortened applicators remained unchanged from those of the standard applicators. Penumbrae were broadened by 0-3 mm depending on electron energy and depth as the air gap was increased from 5 cm (standard applicator at SSD = 100 cm) to 10 cm (shortened applicator at SSD = 95 cm). The dose calculation performance of the modified applicators at 95 cm < SSD < 100 cm was considered similar as with standard applicators at SSD = 100 cm using the Gaussian pencil beam electron dose calculation algorithm of the treatment planning system (Varian Eclipse). The modified isocentric treatment technique for PMRT was superior than the traditional two-dimensional technique. However, with the tangential photon fields without electrons the even better dose uniformity within PTV could be achieved but with increased irradiation of healthy tissues (lung, heart, and contralateral breast). The modified isocentric technique was also found faster than the traditional technique with SSD = 100 cm fields.

Conclusions

It is possible to apply an isocentric treatment technique in PMRT with electrons and photons. The homogeneity of the dose distribution can be improved by adding more photon field segments. With the isocentric technique it is possible to achieve even some time sparing in treatment delivery compared with the traditional SSD = 100 cm technique.     

Exclusive MRI-based tandem and colpostats reconstruction in gynaecological brachytherapy treatment planning

Purpose

According to the GYN GEC-ESTRO Recommendations, MRI is needed with the modality of T2 weighted. CT-MR compatible tandem plus colpostats (T/C) (Nucletron) is widely used in cervical brachytherapy. The major challenge of MRI is the lack of dummy catheters. Therefore, an additional imaging modality is usually required. One disadvantage of sliced-based reconstruction is that resolution in longitudinal directions can be affected by the slice thickness. The aim of this study is to present a modified T/C applicator in which the catheter visibility is significantly improved.

Methods and materials

A modification to the existing T/C applicator has been made available, increasing the catheter entrance diameter. It allows a greater dummy catheter diameter, and consequently it can be filled with more material per unit length. Visibility was studied with different materials.

Results

The catheter filled with saline water plus iodine compound was clearly seen in both axial and longitudinal acquisitions. To avoid uncertainties introduced by the slice thickness, a simple procedure is presented using longitudinal acquisitions.

Conclusions

The modified applicator plus catheter allows a powerful signal in T2 weighted MRI, using a very simple and accessible material. Also, a method is proposed to solve the problem of the uncertainty derived from slice thickness using few longitudinal acquisitions.     

Surgical treatment of primary melanoma of the umbilicus with sentinel lymph node biopsy and plastic reconstruction: Case report and review of the literature

Aims, patients and methods

The umbilical melanoma is rare, and the surgical treatment can create difficulties for both radical excision and plastic reconstruction. Our aims are to present a case of primary melanoma of the umbilicus and to discuss the best surgical treatment, as well as review the relevant literature.

Results

Surgical excision of primary melanoma of the umbilicus must be carried out to reach the peritoneum. Sentinel lymph node biopsy must be carried as well as plastic reconstruction.

Conclusion

Despite the progress in new medical therapy for melanoma, suitable surgical excision is, at present, the only treatment able to improve patient prognosis. In this report we describe the surgical treatment and plastic reconstruction of a case of umbilical melanoma.     

Race and intensity of post-remission therapy in acute myeloid leukemia

Background

In many cancers, including AML, blacks have poorer overall survival. We investigated whether differences in post-remission therapy (PRT) were a contributing factor.

Methods

We compared PRT cycle number and intensity and time to PRT in blacks and whites, among 460 patients with newly diagnosed AML.

Results

Blacks and whites had PRT of equal cycle intensity and number, but black patients experienced a significant delay in starting PRT (2.73 months in blacks vs. 1 month in whites, p = 0.047). Overall survival was equivalent in blacks and whites.

Conclusion

PRT is delayed in blacks but does not explain differences in survival.     

Trans-abdominal ultrasound (US) and magnetic resonance imaging (MRI) correlation for conformal intracavitary brachytherapy in carcinoma of the uterine cervix

Purpose

Trans-abdominal ultrasonography (US) is capable of determining size, shape, thickness, and diameter of uterus, cervix and disease at cervix or parametria. To assess the potential value of US for image-guided cervical cancer brachytherapy, we compared US-findings relevant for brachytherapy to the corresponding findings obtained from MR imaging.

Materials and methods

Twenty patients with biopsy proven cervical cancer undergoing definitive radiotherapy with/without concomitant Cisplatin chemotherapy and suitable for brachytherapy were invited to participate in this study. US and MR were performed in a similar reproducible patient positioning after intracavitary application. US mid-sagittal and axial image at the level of external cervical os was acquired. Reference points D1 to D9 and distances were identified with respect to central tandem and flange, to delineate cervix, central disease, and external surface of the uterus.

Results

Thirty-two applications using CT/MR compatible applicators were evaluable. The D1 and D3 reference distances which represent anterior surface had a strong correlation with R = 0.92 and 0.94 (p < 0.01). The D2 and D4 reference distances in contrast, which represent the posterior surface had a moderate (D2) and a strong (D4) correlation with R = 0.63 and 0.82 (p < 0.01). Of all, D2 reference distance showed the least correlation of MR and US. The D5 reference distance representing the fundal thickness from tandem tip had a correlation of 0.98. The reference distances for D6, D7, D8, and D9 had a correlation of 0.94, 0.82, 0.96, and 0.93, respectively.

Conclusions

Our study evaluating the use of US, suggests a reasonably strong correlation with MR in delineating uterus, cervix, and central disease for 3D conformal intracavitary brachytherapy planning.     

Multiple breath-hold CBCT for online image guided radiotherapy of lung tumors: Simulation with a dynamic phantom and first patient data

Background and Purpose

Computer controlled breath-hold effectively reduces organ motion for image-guided precision radiotherapy of lung tumors. However, the acquisition time of 3D cone-beam-CT (CBCT) exceeds maximum breath-hold times. We have developed an approach enabling online verification using CBCT image acquisition with ABC®-based breath-hold.

Methods

Patient CBCT images were acquired with ABC®-based repeat breath-hold. The clinical situation was also simulated with a Motion Phantom. Reconstruction of patient and phantom images with selection of free-breathing and breath-hold projections only was performed.

Results

CBCT-imaging in repeat breath-hold resulted in a precisely spherical appearance of a tumor-mimicking structure in the phantom. A faint “ghost” structure (free-breathing phases) can be clearly discriminated. Mean percentage of patient breath-hold time was 66%. Reconstruction based on free-breathing-only shows blurring of both tumor and diaphragm, reconstruction based on breath-hold projections only resulted in sharp contours of the same structures. From the phantom experiments, a maximal repositioning error of 1 mm in each direction can be estimated.

Discussion and Conclusion

CBCT during repetitive breath hold provides reliable soft-tissue-based positioning. Fast 3D-imaging during one breath-hold is currently under development and has the potential to accelerate clinical linac-based volume imaging.     

Clinical introduction of a linac head-mounted 2D detector array based quality assurance system in head and neck IMRT

Background and purpose

IMRT QA is commonly performed in a phantom geometry but the clinical interpretation of the results in a 2D phantom plane is difficult. The main objective of our work is to move from film measurement based QA to 3D dose reconstruction in a patient CT scan. In principle, this could be achieved using a dose reconstruction method from 2D detector array measurements as available in the COMPASS system (IBA Dosimetry). The first step in the clinical introduction of this system instead of the currently used film QA procedures is to test the reliability of the dose reconstruction. In this paper we investigated the validation of the method in a homogeneous phantom with the film QA procedure as a reference. We tested whether COMPASS QA results correctly identified treatment plans that did or did not fulfil QA requirements in head and neck (H&N) IMRT.

Materials and methods

A total number of 24 treatments were selected from an existing database with more than 100 film based H&N IMRT QA results. The QA results were classified as either good, just acceptable or clinically rejected (mean gamma index <0.4, 0.4-0.5 or >0.5, respectively with 3%/3 mm criteria). Film QA was repeated and compared to COMPASS QA with a MatriXX detector measurement performed on the same day.

Results

Good agreement was found between COMPASS reconstructed dose and film measured dose in a phantom (mean gamma 0.83 ± 0.09, 1SD with 1%/1 mm criteria, 0.33 ± 0.04 with 3%/3 mm criteria). COMPASS QA results correlated well with film QA, identifying the same patients with less good QA results. Repeated measurements with film and COMPASS showed changes in delivery after a modified MLC calibration, also visible in a standard MLC check in COMPASS. The time required for QA reduced by half by using COMPASS instead of film.

Conclusions

Agreement of COMPASS QA results with film based QA supports its clinical introduction for a phantom geometry. A standard MLC calibration check is sensitive to <1 mm changes that could be significant in H&N IMRT. These findings offer opportunities to further investigate the method based on a 2D detector array to 3D dose reconstruction in a patient anatomy.     

Radiation-induced microenvironments - The molecular basis for free flap complications in the pre-irradiated field?

Background and purpose

The effect of preoperative radio- or radiochemotherapy on the survival of free flaps used for head and neck reconstruction is reported in a contradictory way. Although there is a lot of knowledge on radiation-induced wound healing disorders from animal models there are no investigations on human patients so far. Our prospective study aimed at clarifying the effect of radiotherapy on clinically apparent free flap complications and on correlating them with radiation-induced extracellular matrix (ECM) remodeling.

Materials and methods

Healing of 114 free flaps was monitored in a prospective study and correlated with different anamnestic features, such as diabetes and radio- or radiochemotherapy using multivariate regression. During the operation connective tissue biopsies were harvested from the graft beds and analyzed for Transforming Growth Factor (TGF)-β₁-expression by means of Western blotting as well as Tissue Inhibitor of Matrix-Metallo-Proteinase (TIMP)-1 and Matrix-Metallo-Proteinase (MMP)-1 by immunohistochemistry.

Results

History of radio- or radiochemotherapy was the only factor significantly predicting free flap complications. Radiochemotherapy resulted in a significant increase in TGF-β₁- and TIMP-1-expression, while MMP-1-expression was not significantly altered. Radiotherapy alone significantly increased TIMP-1-expression without detectable effects on TGF-β₁ and MMP-1.

Conclusions

Radio- and radiochemotherapy alter graft bed ECM organization prior to surgery. This alteration impacts significantly on free flap survival in the pre-irradiated field.     

The potential for induction peptide receptor chemoradionuclide therapy to render inoperable pancreatic and duodenal neuroendocrine tumours resectable

Aims

To assess the clinical utility of peptide receptor chemoradionuclide therapy (PRCRT) using ¹⁷⁷Lu-octreotate (LuTate) with concurrent 5FU chemotherapy in patients with inoperable primary pancreatic and duodenal neuroendocrine tumours (NETs).

Methods

Between December 2006 and October 2009, five patients with progressive inoperable pancreatic and duodenal NETs without distant metastatic disease or with a potentially resectable solitary distant metastasis were treated with PRCRT; in combination with external beam radiotherapy in one case. Patients were followed up three months post-treatment with somatostatin receptor scintigraphy, radiology, biochemical markers and clinical assessment. Radiological response classification was defined by Response Evaluation Criteria in Solid Tumours (RECIST) with the addition of a minor response (MR; 10-30% size reduction) classification. Long-term follow up was performed until July 2011.

Results

At three months post-treatment, all five patients had a scintigraphic response, four had a radiological response and three of the four symptomatic patients responded clinically. All five patients had an ongoing treatment response beyond three months including one where further tumour shrinkage facilitated curative surgery. All five patients are alive with 12-42 months of follow-up post-treatment.

Conclusion

PRCRT can be effective in inoperable pancreatic and duodenal neuroendocrine tumours and may play a role as neoadjuvant therapy in this patient group.     

Prognostic significance of triple negative breast cancer at tumor size 1 cm and smaller

Aims

The purpose of this study was to clarify the prognostic significance of triple-negative breast cancer (TNBC) with a tumor size ≤ 1 cm.

Materials and methods

Patients with primary operable breast cancer with a tumor size ≤ 1 cm were enrolled at Changhua Christian Hospital and National Cheng-Kung University Hospital. Tumors negative for ER, PR, and HER-2 were classified as TNBCs and compared with tumors with any receptor positivity (non-TNBC) for disease-free survival (DFS) and cancer-specific survival (CSS).

Results

From 1995 to 2006, a total of 377 patients with tumor size ≤ 1 cm were enrolled. Compared with non-TNBC patients, TNBC patients with a tumor size ≤ 1 cm as a whole or in a lymph node-positive subgroup were not associated with a poorer 5-year DFS and CSS. In lymph node-negative patients (pT1a-bN0M0), TNBC was associated with a poorer 5-year CSS but not DFS. Compared with the hormone receptor-positive, HER-2-negative subgroup, TNBC was associated with poorer DFS and CSS. In the multivariate Cox regression hazard analysis, lymph node invasion was the most important cause of disease recurrence and cancer-specific death.

Conclusion

TNBC is very likely an independent risk factor in small (≤1 cm) node-negative invasive breast cancer. With tumors 1 cm and smaller, lymph node invasion was the single most important prognostic factor.     

Electromagnetic thermotherapy using fine needles for hepatoma treatment

Background and aims

Hepatocellular carcinoma can be treated with heat-based therapies, especially radiofrequency ablation (RFA). However, RFA has limited efficacy and is quite expensive. We designed a new system using fine needles combined with an alternating magnetic field to generate hyperthermia for the treatment of hepatocellular carcinoma in a rat hepatoma model. Our aims are to assess the efficacy of our method and determine survival up to 30 days.

Methods

An N1-S1 cell line was inoculated into the livers of Sprague-Dawley rats, generating tumors after 14 days. The animals were randomized into 5 groups and treated after laparotomy either with normal saline (group I), iron oxide nanoparticles (group II), fine needles (group III), fine needles and iron oxide nanoparticles combined (group IV) or self-designed two-part needles placed under ultrasonographic guidance percutaneously (group V). Every rat was placed in an alternating magnetic field. The temperature in the treatment area was maintained between 55 and 60 °C. At day 30 after treatment, tumor volumes and mortality were assessed and histology samples were studied.

Results

Tumor volumes were significantly reduced and survival rate was prolonged in groups III, IV and V versus groups I and II (P < 0.05). On pathological examination, groups III, IV and V presented obvious necrosis, apoptosis, calcifications and inflammatory changes in the treatment area.

Conclusion

Our study demonstrates that hyperthermia generated by fine stainless-steel needles combined with an alternating magnetic field effectively inhibits hepatoma growth in rats and prolongs their survival. Further, this method can be applied percutaneously under ultrasonographic guidance.