Repeated tumor pO2 measurements by multi-site EPR oximetry as a prognostic marker for enhanced therapeutic efficacy of fractionated radiotherapy

Purpose

To investigate the temporal effects of single or fractionated radiotherapy on subcutaneous RIF-1 tumor pO₂ and to determine the therapeutic outcomes when the timing of fractionations is guided by tumor pO₂.

Methods

The time-course of the tumor pO₂ changes was followed by multi-site electron paramagnetic resonance (EPR) oximetry. The tumors were treated with single 10, 20, and 10 Gy × 2 doses, and the tumor pO₂ was measured repeatedly for six consecutive days. In the 10 Gy × 2 group, the second dose of 10 Gy was delivered at a time when the tumors were either relatively oxygenated or hypoxic. The changes in tumor volumes were followed for nine days to determine the therapeutic outcomes.

Results

A significant increase in tumor pO₂ was observed at 24 h post 10 Gy, while 20 Gy resulted in a significant increase in tumor pO₂ at 72-120 h post irradiation. The tumors irradiated with a second dose of 10 Gy at 24 h, when the tumors were oxygenated, had a significant increase in tumor doubling times (DTs), as compared to tumors treated at 48 h when they were hypoxic (p < 0.01).

Conclusion

Results indicate that the time of tumor oxygenation depends on the irradiation doses, and radiotherapeutic efficacy could be optimized if irradiations are scheduled at times of increased tumor oxygenation. In vivo multi-site EPR oximetry could be potentially used to monitor tumor pO₂ repeatedly during fractionated schemes to optimize radiotherapeutic outcome. This technique could also be used to identify responsive and non-responsive tumors, which will facilitate the design of other therapeutic approaches for non-responsive tumors at early time points during the course of therapy.     

Real-time dynamic MLC tracking for inversely optimized arc radiotherapy

Background and purpose

Motion compensation with MLC tracking was tested for inversely optimized arc radiotherapy with special attention to the impact of the size of the target displacements and the angle of the leaf trajectory.

Materials and methods

An MLC-tracking algorithm was used to adjust the MLC positions according to the target movements using information from an optical real-time positioning management system. Two plans with collimator angles of 45° and 90°, respectively, were delivered and measured using the Delta⁴® dosimetric device moving in the superior-inferior direction with peak-to-peak displacements of 5, 10, 15, 20 and 25 mm and a cycle time of 6 s.

Results

Gamma index evaluation for plan delivery with MLC tracking gave a pass rate higher than 98% for criteria 3% and 3 mm for both plans and for all sizes of the target displacement. With no motion compensation, the average pass rate was 75% for plan 1 and 70% for plan 2 for 25 mm peak-to-peak displacement.

Conclusion

MLC tracking improves the accuracy of inversely optimized arc delivery for the cases studied. With MLC tracking, the dosimetric accuracy was independent of the magnitude of the peak-to-peak displacement of the target and not significantly affected by the angle between the leaf trajectory and the target movements.     

Geometric accuracy of a novel gimbals based radiation therapy tumor tracking system

Purpose

VERO is a novel platform for image guided stereotactic body radiotherapy. Orthogonal gimbals hold the linac-MLC assembly allowing real-time moving tumor tracking. This study determines the geometric accuracy of the tracking.

Materials and methods

To determine the tracking error, an 1D moving phantom produced sinusoidal motion with frequencies up to 30 breaths per minute (bpm). Tumor trajectories of patients were reproduced using a 2D robot and pursued with the gimbals tracking system prototype. Using the moving beam light field and a digital-camera-based detection unit tracking errors, system lag and equivalence of pan/tilt performance were measured.

Results

The system lag was 47.7 ms for panning and 47.6 ms for tilting. Applying system lag compensation, sinusoidal motion tracking was accurate, with a tracking error 90% percentile E_90% < 0.82 mm and similar performance for pan/tilt. Systematic tracking errors were below 0.14 mm. The 2D tumor trajectories were tracked with an average E_90% of 0.54 mm, and tracking error standard deviations of 0.20 mm for pan and 0.22 mm for tilt.

Conclusions

In terms of dynamic behavior, the gimbaled linac of the VERO system showed to be an excellent approach for providing accurate real-time tumor tracking in radiation therapy.     

A methodology for incorporating functional bone marrow sparing in IMRT planning for pelvic radiation therapy

Background and purpose

The purpose of this study was to design a radiation therapy treatment planning approach that would spare hematopoietically active bone marrow using [¹⁸F]FLT PET imaging.

Materials and methods

We have developed an IMRT planning methodology to incorporate functional PET imaging using [¹⁸F]FLT scans. Plans were generated for two simulated cervical cancer patients, where pelvic active bone marrow regions were incorporated as avoidance regions based on the ranges: SUV4 ? 4; 4 > SUV3 ? 3; and 3 > SUV2 ? 2. Dose objectives were set to reduce bone marrow volume that received 10 (V₁₀) and 20 (V₂₀) Gy.

Results

Active bone marrow regions identified by [¹⁸F]FLT with an SUV ? 2, SUV ? 3, and SUV ? 4 represented an average of 43.0%, 15.3%, and 5.8%, respectively of the total osseous pelvis for the two cases studied. Improved dose-volume histograms for all identified bone marrow SUV volumes and decreases in V₁₀, and V₂₀ were achieved without clinically significant changes to PTV or OAR doses.

Conclusions

Incorporation of [¹⁸F]FLT PET in IMRT planning provides a methodology to reduce radiation dose to active bone marrow without compromising PTV or OAR dose objectives in pelvic malignancies.     

Accessing radiation response using hypoxia PET imaging and oxygen sensitive electrodes: A preclinical study

Purpose

Tumor hypoxia is a known cause of resistance to radiotherapy. The aim of this study was to investigate the prognostic value of hypoxia measured by ¹⁸F-fluoroazomycin arabinoside (¹⁸F-FAZA) PET or the Eppendorf oxygen electrode in a pre-clinical tumor model.

Material/methods

Pretreatment ¹⁸F-FAZA PET scans and blood sampling was conducted in 92 Female CDF1 mice with subcutaneous C3H mammary carcinomas grown in the right foot. Similarly, oxygenation status of 80 equivalent tumors was assessed using an invasive oxygen sensitive electrode. Tumors were then irradiated with a single dose of 55 Gy and local tumor control up to 90 days after the treatment was determined.

Results

A significant difference in local tumor control between “more hypoxic” or “less hypoxic” groups separated either by a median ¹⁸F-FAZA PET determined tumor-to-blood ratio (P = 0.007; hazard ratio, HR = 0.21 [95% CI: 0.06-0.74]), or the fraction of oxygen partial pressure (pO₂) values ?2.5 mmHg (P = 0.018; HR = 0.31 [95% CI: 0.11-0.87]), was found. Both assays showed that the more hypoxic tumors had significantly lower tumor control.

Conclusion

¹⁸F-FAZA PET analysis showed that pre treatment tumor hypoxia was prognostic of radiation response. Similar results were obtained when oxygenation status was assessed by the Eppendorf pO₂ Histograph. The results of this study support the role of ¹⁸F-FAZA as a non-invasive prognostic marker for tumor hypoxia.     

Adaptive 18fluoro-2-deoxyglucose positron emission tomography/computed tomography-based target volume delineation in radiotherapy planning of head and neck cancer

Aims

This study investigated an adaptive threshold-based method to delineate the target volume using ¹⁸fluoro-2-deoxyglucose (¹⁸FDG) positron emission tomography/computed tomography (PET/CT) before and during a course of radical radiotherapy or chemoradiotherapy in locally advanced squamous cell carcinoma of the head and neck.

Materials and methods

Ten patients were enrolled between March 2006 and May 2008. ¹⁸FDG PET/CT scans were carried out 72 h before the start of radiotherapy and then at three time points during radiotherapy (8-18, 36-50 and 66 Gy). Functional volumes were delineated using an adaptive iterative algorithm weighted according to the mean standard uptake value (SUV_mean) within the region of interest. The background ¹⁸FDG uptake, maximum standard uptake value (SUV_max) and SUV_mean within the volumes were assessed.

Results

There was no significant reduction in the primary target volumes defined by the adaptive threshold during radiotherapy. However, the SUV_max significantly reduced within the primary (P = 0.003-0.011) and lymph node (P < 0.0001) target volume at 36-50 and 36-66 Gy compared with 0 Gy. The SUV_mean was negatively correlated to radiation dose (P < 0.0001-0.014). The ratio between the background uptake of ¹⁸FDG and the SUV_mean significantly reduced for both the lymph node target volume at 36-50 Gy and the primary volume at 66 Gy. The lack of significant correlation between the defined volume and radiation dose was because the SUV_mean within the region of interest used to define the edge of the volume was equal to or less than the background ¹⁸FDG uptake and the software was unable to effectively differentiate between tumour and background uptake.

Conclusions

The adaptive threshold method may be of benefit when used to define the target volume before the start of radiotherapy. This method was not beneficial during radiotherapy because the software is not sensitive enough to distinguish tumour from background and define a volume. ¹⁸FDG PET/CT-guided volumes delineated by automatic adaptive thresholding methods should only be used for dose escalation with the pretreatment imaging.     

Comparison of (immuno-)fluorescence data with serial [F]Fmiso PET/CT imaging for assessment of chronic and acute hypoxia in head and neck cancers

Purpose

Both, acute and chronic hypoxia can have unfavorable impacts on tumor progression and therapy response. The aim of this study was to optimize a macroscopic technique for the quantification of acute and chronic hypoxia (Wang model assessment of serial [¹⁸F]Fmiso PET/CT imaging) by comparing with a microscopic technique [(immuno-)fluorescence staining in tumor cryosections].

Materials and methods

Tumor pieces from the human squamous cell carcinoma lines from the head and neck FaDu and CAL33 were xenografted into the hind leg of NMRI nu/nu mice. Tumor-bearing mice were placed on an in-house developed multi-point fixation system and subjected to two consecutive dynamic [¹⁸F]Fmiso PET/CTs within a 24 h interval. The Wang model was applied to SUV (standard uptake values) to quantify the fractions of acute and chronic hypoxia. Hypoxia subtypes were also assessed in vital tumor tissue of cryosections from the same tumors for (immuno-)fluorescence distributions of Hoechst 33342 (perfusion), pimonidazole (hypoxia), and CD31 (endothelium) using pattern recognition in microcirculatory supply units (defined as vital tumor tissue area supplied by a single microvessel).

Results

Using our multi-point fixation system, acceptable co-registration (registration errors ε ranged from 0.34 to 1.37) between serial PET/CT images within individual voxels was achieved. The Wang model consistently yielded higher fractions of acute hypoxia than the MCSU method. Through specific modification of the Wang model (Wang_mod), it was possible to reduce the fraction of acute hypoxia. However, there was no significant correlation between the fractions of acute hypoxia in individual tumors assessed by the Wang_mod model and the MCSU method for either tumor line (FaDu: r = 0.68, p = 0.21 and CAL33: r = 0.71, p = 0.18). This lack of correlation is most-likely due to the difference between the non-linear uptake of [¹⁸F]Fmiso and the spatial assessment of MCSUs.

Conclusions

Whether the Wang model can be used to predict radiation response after serial [¹⁸F]Fmiso PET imaging, needs to be confirmed in experimental and clinical studies.     

Correlating quantitative MR measurements of standardized tumor lines with histological parameters and tumor control dose

Purpose

To correlate non-invasively acquired radiobiologically relevant magnetic resonance (MR) parameters with functional histology and tumor control doses (TCD₅₀).

Materials and methods

The MR parameters relative perfusion, re-oxygenation and lactate (Lac) concentration from eight human xenograft squamous tumor lines were compared with the histologically acquired pimonidazole hypoxic fraction, the perfused vessel area and TCD₅₀.

Results

Good spatial correlation in the parameter maps could be observed between the pimonidazole staining and tumor regions, which can be reoxygenated when breathing carbogen. A strong positive correlation (R = 0.74) was found between whole tumor pimonidazole hypoxic fraction and re-oxygenation, as one would expect. A good correlation was also observed between Lac concentration and re-oxygenation (R = 0.71) and between TCD₅₀ and re-oxygenation (R = 0.64), whereas Lac and TCD₅₀ showed a moderate relation (R = 0.44). The in vivo measurement of relative perfusion could be validated to reflect the perfused vessel area (R = 0.63). No correlation was detected between perfusion and re-oxygenation or TCD₅₀.

Conclusions

Lac and re-oxygenation were shown to be pretreatment predictive markers independent from the pathophysiological changes induced during a fractionated course of radiotherapy. These parameters hold promise to be acquired non-invasively with results just a few minutes after measurement and to tailor radiotherapy to individual patterns of a tumor microenvironment.     

Prognostic impact of postoperative, pre-irradiation F-fluoroethyl-l-tyrosine uptake in glioblastoma patients treated with radiochemotherapy

Background and purpose

Resection is considered as essential for the efficacy of modern adjuvant treatment of glioblastoma multiforme (GBM). Previous studies have indicated that amino acid PET is more specific than contrast enhancement on MRI for detecting residual tumor tissue after surgery. In a prospective study we investigated the prognostic impact of postoperative tumor volume and tumor/brain ratios (TBR) in PET using O-(2-[¹⁸F]fluoroethyl)-l-tyrosine (FET) in comparison with MRI.

Materials and methods

Forty-four patients with GBM were investigated by FET PET and MRI after surgery. Tumor volume in FET PET with a tumor/brain ratio (TBR) > 1.6 and a TBR > 2, mean and maximum TBR and gadolinium contrast-enhancement on MRI (Gd-volume) were determined. Thereafter patients received a fractionated radiotherapy with concomitant temozolomide (RCX). The median follow-up was 15.4 (3-35) months. The prognostic value of postoperative residual tumor volume in FET PET, TBR_mean, TBR_max and Gd-volume was evaluated using Kaplan-Maier estimates for disease-free survival (DFS) and overall survival (OS).

Results

Postoperative tumor volume in FET PET had a significant independent influence on OS and DFS (OS 20.0 vs. 6.9 months; DFS 9.6 vs. 5.1 months, p < 0.001; cut-off 25 ml). Similar results were observed when a TBR ? 2 (cut-off 10 ml) was used to define the tumor volume in ¹⁸F-FET PET. The TBR_mean and TBR_max of FET uptake had a significant influence on DFS (p < 0.05). Gd-volume in MRI had significant effect on OS and DFS in the univariate analysis. No independent significant influence in OS or DFS could be observed for Gd-volume in MRI.

Conclusions

Our data indicate that the tumor volume in FET PET after surgery of GBM has a strong prognostic impact for these patients. FET PET appears to be helpful to determine the residual tumor volume after surgery of GBM and may serve as a valuable tool for optimal planning of radiation treatment.     

Quantitative Perfusion Scintigraphy or Anatomic Segment Method in lung cancer resection

Background

Quantitative Perfusion Scintigraphy (QPS) and Anatomic Segment Method (ASM) are two techniques for estimating postoperative pulmonary function. QPS is gold standard, but holds disadvantages.

Aim

Could ASM substitute QPS in the preoperative work-up of NSCLC?

Methods

Retrospective study in patients with NSCLC or mesothelioma undergoing resection. FEV1 and DL,CO were estimated by QPS and ASM and compared to pulmonary function measured 3 months after resection. Correlation tests and Bland-Altman analyses were performed.

Results

40 patients (23 lobectomies, 14 pneumonectomies). Both methods correlated similarly with postoperative FEV₁ (QPSρ = 0.69; ASMρ = 0.75) and DL,CO (QPSρ = 0.70; ASMρ = 0.74). Correlation between both methods was high (ppoFEV₁ρ = 0.89; ppoDL,COρ = 0.89). The same principles applied in a subgroup analysis of patients with COPD. Bland-Altman analyses showed that ASM underestimated postoperative FEV₁ and DL,CO more than QPS in all groups.

Conclusion

QPS and ASM are remarkably similar in predicting postoperative pulmonary function. As ASM underestimates pulmonary function more, it could be a safe alternative from a cost-benefit point of view. Based on these results, it appears that QPS could be restricted to patients in whom ASM suggests functional inoperability, although further prospective studies are necessary.     

Postmastectomy intensity modulated radiation therapy following immediate expander-implant reconstruction

Background/purpose

To evaluate radiation plans of patients undergoing mastectomy with immediate expander-implant reconstruction followed by postmastectomy radiation therapy (PMRT).

Materials/methods

We identified 41 patients from June 2004 to May 2007 who underwent mastectomy, immediate expander-implant reconstruction, and PMRT with intensity-modulated radiation therapy. We assessed chest wall (CW) coverage and volume of heart and lung irradiated.

Results

In 73% of patients, all CW borders were adequately covered, and in 22%, all but 1 border were adequately covered. The total lung V₂₀ was <20% in 39/41 patients. The mean lung V₂₀ was 13% (range, 3-23%), and the mean heart D_mean was 2.81 Gy (range, 0.53-9.60 Gy). In patients with left-sided lesions without internal mammary nodes (IMNs) treatment (n = 22), the mean lung V₂₀ was 12.6% and the mean heart D_mean was 3.90 Gy, and in the patient with IMN treatment, the lung V₂₀ was 18% and heart D_mean was 8.04 Gy. For right-sided lesions without IMN treatment (n = 12), the mean lung V₂₀ was 12.4% and the mean heart D_mean was 0.90 Gy, and in patients with IMN treatment (n = 6), these numbers were 17.8% and 1.76 Gy. At a median follow-up of 29 months, the 30-month actuarial local control was 97%.

Conclusions

In women undergoing immediate expander-implant reconstruction, PMRT can achieve excellent local control with acceptable heart and lung doses. These results can be achieved even when the IMN are being treated, although doses to the heart and lungs will be higher.     

Increasing treatment accuracy for cervical cancer patients using correlations between bladder-filling change and cervix-uterus displacements: Proof of principle

Purpose

To investigate application of pre-treatment established correlations between bladder-filling changes and cervix-uterus displacements in adaptive therapy.

Materials and methods

Thirteen cervical cancer patients participated in this prospective study. Pre-treatment, and after delivery of 40 Gy, a full bladder CT-scan was acquired, followed by voiding the bladder and acquisition of 4 other 3D scans in a 1 h period with a naturally filling bladder (variable bladder filling CT-scans, VBF-scans). For the pre-treatment VBF-scans, linear correlations between bladder volume change and displacements of the tip of the uterus (ToU) and the center of mass (CoM) of markers implanted in the fornices of the vagina relative to the full bladder planning scan were established. Prediction accuracy of these correlation models was assessed by comparison with actual displacements in CT-scans, both pre-treatment and after 40 Gy. Inter-fraction ToU and marker-CoM displacements were derived from the established correlations and twice-weekly performed in-room bladder volume measurements, using a 3D ultrasound scanner.

Results

Target displacement in VBF-scans ranged from up to 65 mm in a single direction to almost 0 mm, depending on the patient. For pre-treatment VBF-scans, the linear correlation models predicted the mean 3D position change for the ToU of 26.1 mm ± 10.8 with a residual of only 2.2 mm ± 1.7. For the marker-CoM, the 8.4 mm ± 5.3 mean positioning error was predicted with a residual of 0.9 mm ± 0.7. After 40 Gy, the mean ToU displacement was 26.8 mm ± 15.8, while prediction based on the pre-treatment correlation models yielded a mean residual error of 9.0 mm ± 3.7. Target positioning errors in the fractioned treatments were very large, especially for the ToU (−18.5 mm ± 11.2 for systematic errors in SI-direction).

Conclusions

Pre-treatment acquired VBF-scans may be used to substantially enhance treatment precision of cervical cancer patients. Application in adaptive therapy is promising and warrants further investigation. For highly conformal (IMRT) treatments, the use of a full bladder drinking protocol results in unacceptably large systematic set-up errors.     

Diagnostic and staging impact of radiotherapy planning FDG-PET-CT in non-small-cell lung cancer

Background and purpose

To evaluate whether FDG-PET performed for radiotherapy (RT) planning can detect disease progression, compared with staging PET.

Materials and methods

Twenty-six patients with newly-diagnosed non-small-cell lung cancer underwent planning PET-CT for curative RT within 8 weeks (mean: 33 ± 14 days) of staging PET-CT. Progressive disease (PD) was defined as >25% increase in tumour size (transaxial) or volume, as delineated by SUV threshold of 2.5, or new sites (SUV > 2.5).

Results

The planning PET detected PD in 16 patients (61%), compared to four patients (15%) by CT component of PET-CT. The mean scan interval was longer in patients with progression: 40 ± 12 days, compared to 22 ± 11 days without progression. Planning PET detected PD in 13/17 (76%), 12/14 (86%) and 7/7 patients if the interval was ?4, 5 and 6 weeks, respectively, compared with 3/9 patients if interval <4 weeks. Planning PET detected PD in primary metabolic volume in seven patients, 20 new nodal sites in 12 new nodal stations and nine patients, five extra-nodal sites in five patients. This resulted in upstaging in nine patients (35%): stage IIIA in three, IIIB in three and IV in three.

Conclusions

RT-planning FDG-PET can provide incremental diagnostic information and may impact on staging in a significant number of patients.     

F-FDG PET bio-metabolic monitoring of neoadjuvant therapy effects in rectal cancer: Focus on nodal disease characteristics

Objective

To evaluate efficacy of ¹⁸F-FDG PET(CT) in the staging and re staging of patients with locally advanced rectal cancer, its potential role in predicting pathological response to neoadjuvant therapy.

Patients and methods

Patients with confirmed diagnosis of rectal cancer (T2-4 or N+) were prospectively studied with ¹⁸F-FDG PET before and after neoadjuvant therapy. Surgery was programmed 4-6 weeks after treatment followed by an expert histological analysis of the surgical specimen. Response to neoadjuvant treatment was assessed using two specific variables: difference in SUV (difSUV) pre/post-neoadjuvant treatment and response index (RI).

Results

A total of 64 patients were enrolled for pathological and bio-metabolic response assessment. Compared to cN0, cN+ patients had a higher SUV₁ mean value (6.5 vs. 7.6, p = 0.04) and ypN+ patients had higher SUV₂ mean values (2.4 vs 3.5, p = 0.06). difSUV values of ?4 was the most efficient diagnostic parameter (sensitivity = 45.8%, specificity = 86.2%, positive predictive value (PPV) = 73.3%, negative predictive value(NPV) = 65.7%). With an RI of 66.6%, the sensitivity was 38.5%, specificity = 81.5%, PPV = 66.6%, and NPV = 57.8%. Patients who experienced disease progression had an RI ? 66% and a difSUV ? 4.

Conclusion

¹⁸F-FDG PET has proven to be an accurate diagnostic technique for assessing rectal cancer response to neoadjuvant therapy. The results in terms of sensitivity, specificity, PPV and NPV were similar, if not superior, to those reported with other diagnostic imaging techniques.     

3D Dosimetric verification of volumetric-modulated arc therapy by portal dosimetry

Background and purpose

To demonstrate the feasibility of back-projection portal dosimetry for accurate 3D dosimetric verification of volumetric-modulated arc therapy (VMAT), pre-treatment as well as in vivo.

Materials and methods

Several modifications to our existing approach were implemented to make the method applicable to VMAT: (i) gantry angle-resolved data acquisition, (ii) calculation of the patient transmission, (iii) compensation for detector ‘flex’ and (iv) 3D dose reconstruction and evaluation.

Results

Planned and EPID-(Electronic Portal Image Detector)-reconstructed dose distributions show good agreement for pre-treatment verification of two prostate, a stereotactic lung and a head-and-neck VMAT plan and for in vivo verification of VMAT treatments of prostate and lung cancer. Averaged over pre-treatment verifications, planned and measured isocentre dose ratios were −1.2% (range [−4.7%,1.8%]). 3D gamma analysis (3% maximum dose, 3 mm) revealed mean γ 〈γ_mean〉 = 0.37 [0.34,0.39], maximum 1% γ 〈γ_1%〉 = 0.72 [0.66,0.81] and percentage of points with γ ? 1 〈P_γ ? 1〉 = 99% [97%,100%]. For in vivo verification, the average isocentre dose ratio was −1.2% [−0.8%,−1.7%], 〈γ_mean〉 = 0.52 [0.40,0.64], 〈γ_1%〉 = 0.92 [0.76,1.08] and 〈P_γ ? 1〉 = 96% [93%,100%].

Conclusions

Our portal dosimetry method was successfully adapted for verification of VMAT treatments, pre-treatment as well as in vivo.     

CT-guided interstitial brachytherapy of inoperable non-small cell lung cancer

Purpose

The aim of this study was to assess the technical feasibility, efficacy, and complications of CT-guided interstitial brachytherapy for treating inoperable non-small cell lung cancer (NSCLC).

Materials and methods

Twenty one patients were included in this prospective study. The median age was 72.6 years (57-85). Tumors were treated with brachytherapy that was positioned under CT-fluoroscopy. The treatment planning system (TPS) was used preoperatively to reconstruct three dimensional images of the tumor and to calculate the estimated seed number and distribution. The median matched peripheral dose (MPD) was 130 Gy (range, 100-160 Gy). All procedures were performed under local anesthesia. A follow-up CT was performed 6 weeks later and every 3 months post implantation.

Results

Follow-up period was 2-30 months. The mean diameter of the 21 lung tumors was 4.6 cm (range, 2.8-6.5 cm). The response rate of pain relief was 83.3% (10/12). The pain-free duration was 0-12 months (median: 6 months; 95% CI: 3-9 months). Overall responding rate (CR + PR) for this group of patients was 71.4%. Local tumor control rate was 85.7%. Six (28.6%) patients died as a result of primary tumor progression; thirteen (61.9%) patients died of multi-organ failure or other metastases. Two (9.5%) patients survived to follow-up. At the time of analysis, the median survival time for all patients was 10 months (95% CI: 6.6-13.4 months), with 1 year and 2 year survival rates were 42.4% and 6.5%, respectively. Median survival time for stage II, stage III, and stage IV was 20 months, 9 months, and 8 months, respectively. No major complications were observed. Minor complications (19%) included mild pneumothorax (n = 1), hemosputum (n = 1), pleural effusion (n = 1), and localized skin erythema (n = 1). None of these complications required further treatment, although hospital discharge was delayed. No ¹²⁵I seeds migrated to other tissues or organs.

Conclusion

Minimally invasive CT-guided interstitial brachytherapy is safe, useful, less complicated and considered as a palliative treatment option for inoperable non-small cell lung cancer.     

The potential advantages of FDG PET/CT-based target volume delineation in radiotherapy planning of head and neck cancer

Purpose

This study investigated two fixed threshold methods to delineate the target volume using ¹⁸FDG PET/CT before and during a course of radical radiotherapy in locally advanced squamous cell carcinoma of the head and neck.

Materials and methods

Patients were enrolled into the study between March 2006 and May 2008. ¹⁸FDG PET/CT scans were carried out 72 h prior to the start of radiotherapy and then at 10, 44 and 66 Gy. Functional volumes were delineated according to the SUV Cut Off (SUVCO) (2.5, 3.0, 3.5, and 4.0 bwg/ml) and percentage of the SUVmax (30%, 35%, 40%, 45%, and 50%) thresholds. The background ¹⁸FDG uptake and the SUVmax within the volumes were also assessed.

Results

Primary and lymph node volumes for the eight patients significantly reduced with each increase in the delineation threshold (for example 2.5-3.0 bwg/ml SUVCO) compared to the baseline threshold at each imaging point. There was a significant reduction in the volume (p ? 0.0001-0.01) after 36 Gy compared to the 0 Gy by the SUVCO method. There was a negative correlation between the SUVmax within the primary and lymph node volumes and delivered radiation dose (p ? 0.0001-0.011) but no difference in the SUV within the background reference region. The volumes delineated by the PTSUVmax method increased with the increase in the delivered radiation dose after 36 Gy because the SUVmax within the region of interest used to define the edge of the volume was equal or less than the background ¹⁸FDG uptake and the software was unable to effectively differentiate between tumour and background uptake.

Conclusions

The changes in the target volumes delineated by the SUVCO method were less susceptible to background ¹⁸FDG uptake compared to those delineated by the PTSUVmax and may be more helpful in radiotherapy planning. The best method and threshold have still to be determined within institutions, both nationally and internationally.     

Daily online bony correction is required for prostate patients without fiducial markers or soft-tissue imaging

Aim

To compare online position verification strategies with offline correction protocols for patients undergoing definitive prostate radiotherapy.

Materials and methods

We analysed 50 patients with implanted fiducial markers undergoing curative prostate radiation treatment, all of whom underwent daily kilovoltage imaging using an on-board imager. For each treatment, patients were set-up initially with skin tattoos and in-room lasers. Orthogonal on-board imager images were acquired and the couch shift to match both bony anatomy and the fiducial markers recorded. The set-up error using skin tattoos and offline bone correction was compared with online bone correction. The fiducial markers were used as the reference.

Results

Data from 1923 fractions were analysed. The systematic error was ≤1 mm for all protocols. The average random error was 2-3 mm for online bony correction and 3-5 mm for skin tattoos or offline-bone. Online-bone showed a significant improvement compared with offline-bone in the number of patients with >5 mm set-up errors for >10% (P < 0.001) and >20% (P < 0.003) of their fractions.

Conclusions

Online correction to bony anatomy reduces both systematic and random set-up error in patients undergoing prostate radiotherapy, and is superior to offline correction methods for those patients not suitable for fiducial markers or daily soft-tissue imaging.     

Rectal dosimetry following prostate brachytherapy with stranded seeds - Comparison of transrectal ultrasound intra-operative planning (day 0) and computed tomography-postplanning (day 1 vs. day 30) with special focus on sources placed close to the rectal wall

Background and purpose

The aim of the study was to compare intra-operative and postplanning at different intervals with special focus on sources placed close to the rectal wall.

Materials and methods

In 61 consecutive patients, CT scans were performed on day 1 and day 30 after an I-125 implant with stranded seeds. The number of sources ?7 mm to the rectal wall was determined, and displacements were analyzed. The angulation of strands relative to rectal wall was compared between intra-operative transrectal ultrasound (TRUS) and both postplanning CT scans.

Results

Sources close to the rectum on day 1 (n = 204) have been the most apical in a strand in 98.5% (n = 201). By comparing day 1 and day 30 data, significant inferior source displacements (mean 3.6 mm; p = 0.02) relative to pelvic bones and a decreasing distance to the rectal wall (mean 1.2 mm; p < 0.01) - consequentially increasing rectal dose - were determined only for sources initially ?3 mm to the rectum. In contrast to an almost parallel arrangement of the needle track and the rectal wall in TRUS, strands and rectal wall converged towards the apex in the postplanning CT scans (mean >30°).

Conclusions

Posterior preplanning margins around the prostate should be particularly limited at the level of the prostate apex.     

Precise correlation between MRI and histopathology - Exploring treatment margins for MRI-guided localized breast cancer therapy

Background

Magnetic resonance imaging (MRI) is more often considered to guide, evaluate or select patients for partial breast irradiation (PBI) or minimally invasive therapy. Safe treatment margins around the MRI-visible lesion (MRI-GTV) are needed to account for surrounding subclinical occult disease.

Purpose

To precisely compare MRI findings with histopathology, and to obtain detailed knowledge about type, rate, quantity and distance of occult disease around the MRI-GTV.

Methods and materials

Patients undergoing MRI and breast-conserving therapy were prospectively included. The wide local excision specimens were subjected to detailed microscopic examination. The size of the invasive (index) tumor was compared with the MRI-GTV. The gross tumor volume (GTV) was defined as the pre-treatment visible lesion. Subclinical tumor foci were reconstructed at various distances to the MRI-GTV.

Results

Sixty-two patients (64 breasts) were included. The mean size difference between MRI-GTV and the index tumor was 1.3 mm. Subclinical disease occurred in 52% and 25% of the specimens at distances ?10 mm and ?20 mm, respectively, from the MRI-GTV.

Conclusions

For MRI-guided minimally invasive therapy, typical treatment margins of 10 mm around the MRI-GTV may include occult disease in 52% of patients. When surgery achieves a 10 mm tumor-free margin around the MRI-GTV, radiotherapy to the tumor bed may require clinical target volume margins >10 mm in up to one-fourth of the patients.