Volumetric response analysis during chemoradiation as predictive tool for optimizing treatment strategy in locally advanced unresectable NSCLC

Purpose

To study the feasibility of measuring volumetric changes in the primary tumor on megavoltage-computed tomography (MVCT) during chemoradiation and to examine the correlation with local response.

Patients and methods

Fifteen consecutive patients with stage III, inoperable, locally advanced non-small cell lung cancer (NSCLC) were treated in a prospective dose escalation study protocol of concurrent chemoradiation. They were monitored for acute toxicity and evaluated with daily MVCT imaging. The volumetric changes were fitted to a negative exponential resulting in a regression coefficient (RC). Local response evaluation was done with positron emission tomography using the radio-labeled glucose analogue F18 fluorodeoxyglucose (FDG-PET).

Results

The mean volume decrease (±standard deviation) was 73% (±18%). With a mean treatment time of 42 days this treatment schedule resulted in a mean decrease of 1.74%/day. Of the 13 evaluable patients seven developed a metabolic complete remission (MCR). The mean RC of the patients with MCR is 0.050 versus a mean RC of 0.023 in non-responders (p = 0.0074). Using a proposed cut-off value for the RC of 0.03 80% of the non-responders will be detected correctly while misclassifying 16.4% of patients who will eventually achieve an MCR. The total cumulative percentage of esophageal grade 3 or more toxicity was 46.7%.

Conclusion

The RC derived from volumetric analysis of daily MVCT is prognostic and predictive for local response in patients treated with chemoradiation for a locally advanced NSCLC. Because this treatment schedule is toxic in nearly half of the patient population, MVCT is a tool in the implementation of patient-individualized treatment strategies.     

Modeling set-up error by daily MVCT for prostate adjuvant treatment delivered in 20 fractions: Implications for the assessment of the optimal correction strategies

Purpose

To optimise image-guided radiotherapy (IGRT) approaches in set-up error correction for hypofractionated adjuvant treatment of prostate cancer using helical tomotherapy (HT).

Methods and materials

HT unit provides megavoltage - CT (MVCT) imaging capability for daily patient set-up. The intrinsic uncertainty of the available image registration techniques was first investigated on a pelvic phantom.To optimise different set-up correction strategies, MVCT data of 37 patients treated with 58 Gy delivered in 20 fractions were analyzed. 620 MVCT images were globally available for the analysis. Daily on-line set-up correction without any action level was applied for 27/37 patients. The residual and the effective set-up error were assessed. For 10/37 patients an off-line correction strategy with an action level was applied.

Results

Phantom measurements showed an intrinsic uncertainty in MVCT imaging and registration around 0.6 mm (±0.5 mm) for each of the three main axes.The minimum value of the residual systematic error was found at 7th-10th session, with values between 0.7 and 1.1 mm (1 SD); a systematic residual error <2 mm for all directions was in any case found at 3th-4th session. This result was also confirmed by the effective systematic set-up error analysis, with a minimum value within 1.5 mm nearly at the 4th or 5th fraction.

Conclusions

Although the minimum systematic residual error is reached at 7th-10th treatment session, the effective systematic set-up error analysis confirmed that an off-line correction at the 4th fraction without any action level may be a robust compromise with a large sparing of time and resources compared to on-line correction.     

Monte Carlo-based analytical model for small and variable fields delivered by TomoTherapy

Background and purpose

Extend to very small fields the validity of a Monte Carlo (MC) based model of TomoTherapy called TomoPen for future implementation of the dynamic jaws feature for helical TomoTherapy.

Materials and methods

First, the modelling of the electron source was revisited using a new method to measure source obscuration for very small fields (<1 cm). The method consisted in MC simulations simulations and measurements of the central dose in a water phantom for a 10 cm × FW field scanned to deliver a 10 × 10 cm² fluence. FW, the longitudinal field width, was varied from 0.4 to 5 cm. The second part of the work consisted of adapting TomoPen to account for any configuration of the jaws in a fast and efficient way by using routinely only the phase-space file of the largest field (5 cm) and interpolated analytical information of phase-space files of smaller field widths.

Results

For the electron source fine tuning, it was shown that the best results were obtained for a 1.1 mm wide spot. Our single phase-space method showed no significant differences compared to MC simulations of various field widths even though only longitudinal intensity and angular analytical functions were applied to the 5 cm phase-space.

Conclusion

The designed model is able to simulate all jaw openings from the 5 cm field phase-space file by applying a bi-dimensional analytical function accounting for the fluence and the angular distribution in the longitudinal direction.     

Volumetric modulated arc therapy versus conventional intensity modulated radiation therapy for stereotactic spine radiotherapy: A planning study and early clinical data

Background and purpose

Outcomes for selected patients with spinal metastases may be improved by dose escalation using stereotactic body radiation therapy (SBRT). As target geometry is complex, we compared SBRT plans using volumetric modulated arc radiotherapy (RapidArc®, RA) and conventional intensity-modulated radiotherapy (IMRT).

Materials and methods

RA and IMRT plans to deliver a fraction of 16 Gy to at least 90% of planning target volume (PTV) were compared for PTV coverage, normal organ sparing and estimated delivery times. Group 1 consisted of PTVs to only vertebral body (n = 3), while group 2 had PTVs encompassing the entire vertebra (n = 4). Finally, RA delivery parameters in four patients were assessed.

Results

Both techniques delivered 16 Gy to a mean of 95% and 85% of the PTV in groups 1 and 2, respectively. Spinal cord sparing was comparable; mean V_{10-partial cord} for RA and IMRT in group 1 was 3.6%, and was 9.4% versus 11.5%, respectively, in group 2. Estimated mean treatment times for RA with 2-3 arcs and IMRT were comparable. Clinical RA beam-on times ranged from 11 to 15.4 min.

Conclusions

Both RA and conventional IMRT plans deliver high quality vertebral SBRT, but plan quality was poorer when the PTV consisted of the entire vertebra.     

Preoperative radio-chemotherapy in early breast cancer patients: Long-term results of a phase II trial

Purpose

This phase II trial aimed to investigate the efficacy of concurrent radio- (RT) and chemotherapy (CT) in the preoperative setting for operable, non-metastatic breast cancer (BC) not amenable to initial breast-conserving surgery (BCS).

Patients and methods

From 2001 to 2003, 59 women were included. CT consisted of four cycles of 5-FU, 500 mg/m²/d, continuous infusion (d1-d5) and vinorelbine, 25 mg/m² (d1 and d6). Starting concurrently with the second cycle, RT delivered 50 Gy to the breast and 46 Gy to the internal mammary and supra/infra-clavicular areas. Breast surgery and lymph node dissection were then performed. Adjuvant treatment consisted of a 16 Gy boost to the tumor bed after BCS, FEC (four cycles of fluorouracil 500 mg/m², cyclophosphamide 500 mg/m², and epirubicin 100 mg/m², d1; d21) for pN1-3 and hormone-therapy for positive hormone receptors BC.

Results

The in-breast pathological complete response rate was 27%. BCS was performed in 41 (69%) pts. Overall and distant-disease free survivals at 5 years were respectively 88% [95% CI 80-98] and 83% [95% CI 74-93] whereas locoregional and local controls were 90% [95% CI 82-97] and 97% [95% CI 92-100]. Late toxicity (CTCAE-V3) was assessed in 51 pts (86%) with a median follow-up of 7 years [5-8]. Four (8%) experienced at least one grade III toxicities (one telangectasia and three fibroses). Cosmetic results, assessed in 35 of the 41 pts (85%) who retained their breasts, were poor in four pts (11%).

Conclusion

Preoperative concurrent administration of RT and CT is an effective regimen. Long-term toxicity is moderate. This association deserves further evaluations in prospective trials.     

The effect of delineation method and observer variability on bladder dose-volume histograms for prostate intensity modulated radiotherapy

Purpose

To quantify the effect of delineation method on bladder DVH, observer variability (OV) and contouring time for prostate IMRT plans.

Materials and methods

Planning CT scans and IMRT plans of 30 prostate cancer patients were anonymized. For 20 patients, 1 observer delineated the bladder using 9 methods. The effect of delineation method on the DVH curve, discrete dose levels and delineation time was quantified. For the 10 remaining CTs, 6 observers delineated bladder wall using 4 methods. Observer-based volume variation and intraclass correlation coefficient (ICC) were used to describe the dosimetric effects of OV.

Results

Manual delineation of the bladder wall (BW_m) was significantly slower than any other method (mean: 20 min vs. ?13 min) and the dosimetric effect of OV was significantly larger (V70 Gy ICC: 0.78 vs. 0.98). Only volumes created using a 2.5 mm contraction from the outer surface, and a method providing a consistent wall volume, showed no notable dosimetric differences from BW_m in both absolute and relative volume.

Conclusions

Automatic contractions from the outer surface provide quicker, more reproducible and reasonably accurate substitutes for BW_m. The widespread use of automatic contractions to create a bladder wall volume would assist in the consistent application of IMRT dose constraints and the interpretation of reported dose.     

DNA methylation changes in cells regrowing after fractioned ionizing radiation

Background and purpose

Repeated exposure to ionizing radiation (IR) can result in adaptive reactions. While DNA methylation changes in adaption to repeated stress exposure are established for a variety of drugs, their role in fractioned ionizing radiation is largely unknown.

Material and methods

MCF7 breast cancer cells were treated 5 times a week with IR in fractions of 2 Gy, resulting in total doses of 10 and 20 Gy. Cells were harvested 48 and 72 h after the last irradiation, as well as after a recovery period of at least 14 d. To identify genes differentially methylated in irradiated versus non-irradiated cells, we used methyl-CpG immunoprecipitation (MCIp) followed by global methylation profiling on CpG island microarrays.

Results

MCIp profiling revealed methylation changes in several CpG islands 48 h after FIR with 10 and 20 Gy. Cells receiving a total dose of 10 Gy started regrowing after 14 d and exhibited similar radioresistance as mock-treated cells. Differential methylation of the CpG units associated with FOXC1 (p < 0.001) and TRAPPC9 (p < 0.001) could be confirmed by time-of-flight mass spectrometry (Sequenom).

Conclusions

In summary, these data indicate that regrowth of MCF7 cells after 10 Gy FIR is associated with locus-specific alterations in DNA methylation.     

Evaluation of the ‘dose of the day’ for IMRT prostate cancer patients derived from portal dose measurements and cone-beam CT

Purpose

High geometrical and dosimetrical accuracies are required for radiotherapy treatments where IMRT is applied in combination with narrow treatment margins in order to minimize dose delivery to normal tissues. As an overall check, we implemented a method for reconstruction of the actually delivered 3D dose distribution to the patient during a treatment fraction, i.e., the ‘dose of the day’. In this article results on the clinical evaluation of this concept for a group of IMRT prostate cancer patients are presented.

Materials and methods

The actual IMRT fluence maps delivered to a patient were derived from measured EPID-images acquired during treatment using a previously described iterative method. In addition, the patient geometry was obtained from in-room acquired cone-beam CT images. For dose calculation, a mapping of the Hounsfield Units from the planning CT was applied. With the fluence maps and the modified cone-beam CT the ‘dose of the day’ was calculated. The method was validated using phantom measurements and evaluated clinically for 10 prostate cancer patients in 4 or 5 fractions.

Results

The phantom measurements showed that the delivered dose could be reconstructed within 3%/3 mm accuracy. For prostate cancer patients, the isocenter dose agreed within −0.4 ± 1.0% (1 SD) with the planned value, while for on average 98.1% of the pixels within the 50% isodose surface the actually delivered dose agreed within 3% or 3 mm with the planned dose. For most fractions, the dose coverage of the prostate volume was slightly deteriorated which was caused by small prostate rotations and small inaccuracies in fluence delivery. The dose that was delivered to the rectum remained within the constraints used during planning. However, for two patients a large degrading of the dose delivery was observed in two fractions. For one patient this was related to changes in rectum filling with respect to the planning CT and for the other to large intra-fraction motion during treatment delivery, resulting in mean underdosages of 16% in the prostate volume.

Conclusions

A method to accurately assess the ‘dose of the day’ was evaluated for prostate cancer patients treated with IMRT. To correct for observed dose deviations off-line dose-adaptive strategies will be developed.     

Weekly paclitaxel with concurrent radiotherapy followed by adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma

Purpose

To evaluate the efficacy and toxicity of weekly paclitaxel with concurrent radiotherapy followed by adjuvant chemotherapy (AC) in patients with locally advanced nasopharyngeal carcinoma (NPC).

Methods and materials

Between 2004 and 2007, 54 patients with locally advanced NPC were included in this protocol. Patient characteristics: median age 48; 69% male; 52% World Health Organization (WHO) III; 50% stage III, 50% stage IV. The patients underwent a course of definitive conventional radiotherapy (70 Gy in 7 weeks with 2 Gy/fraction), with concurrent weekly paclitaxel 35 mg/m² from the first to the sixth week of radiation. AC was started 4 weeks after the end of the radiotherapy (RT), paclitaxel 135 mg/m² on day 1 and cisplatin 30 mg/m² on days 1-3 were administered every 4 weeks for two cycles.

Results

Median follow-up was 32 months. Eighty-five percentage of complete response and 15% partial response were achieved at the time of one month after AC. The 3-year actuarial rate of local regional control was 86%; distant metastases-free survival, progression-free survival and overall survival at 3 years were 81%, 69% and 76%, respectively. Forty-nine (91%) patients completed six courses of concurrent chemotherapy with weekly paclitaxel, and 4 (7%) patients delayed at the second cycle of AC. No patient developed severe acute toxicities.

Conclusions

Weekly paclitaxel with concurrent RT followed by AC is a potentially effective and toxicity tolerable method for locally advanced NPC. Further studies are needed to identify the optimal dose of weekly paclitaxel in this strategy.     

Multiinstitutional study on target volume delineation variation in breast radiotherapy in the presence of guidelines

Purpose

This study aims to determine magnitude, causes and consequences of post-operative breast tumour target volume delineation variation among radiation oncologists in the presence of guidelines.

Materials and methods

Excision cavities, CTVs and PTVs of eight breast cancer patients were delineated on CT scans by 13 Dutch radiation oncologists (observers) from 12 Dutch institutes participating in the international Young Boost Trial. Delineated volumes and conformity indices were determined. CTV delineation variation (SD) was determined for anatomically relevant regions. Non-parametric statistics were performed to establish effects of observers, patient characteristics and regions on delineation variation.

Results

Even in the presence of delineation guidelines considerable delineation variation is present (0.24 < SD < 1.22 cm). Presence of clips or seroma reduced interobserver variation (0.24 < SD < 0.62 cm). Region-specific analysis showed distinct regions of higher variability per patient. This could not always be ascribed to anatomical features, suggesting interobserver variation is not solely due to lack of image quality.

Conclusions

In this study, interobserver delineation variation in breast tumour target volume delineation is larger than, e.g. setup inaccuracies and results from limited reliable visual guidance as well as interpretation differences between observers, despite guidelines. Reduction of delineation variation is essential in view of current developments in planning techniques, particularly for External Partial Breast Irradiation.     

Determining DVH parameters for combined external beam and brachytherapy treatment: 3D biological dose adding for patients with cervical cancer

Purpose

To compare two methods of DVH parameter determination for combined external beam and brachytherapy treatment of cervical cancer.

Materials and methods

Clinical treatment plans from five patients were used in this study. We simulated two applications given with PDR (32 × 60 cGy per application, given hourly) or HDR (4 × 7 Gy in two applications; each application of two fractions of 7 Gy, given within 17 h) standard and optimised treatment plans, all combined with IMRT (25 × 1.8 Gy). Additionally, we simulated an external beam (EBRT) boost to pathological lymph nodes or the parametrium (7 × 2 Gy).We determined D90 of the high-risk CTV (HR-CTV) and D_2cc of bladder and rectum in EQD2 in two ways. (1) ‘Parameter adding’: assuming a uniform contribution of the EBRT dose distribution and adding the values of DVH parameters for the two brachytherapy insertions, and (2) ‘distributions adding’: summing 3D biological dose distributions of IMRT and brachytherapy plans and subsequently determining the values of the DVH parameters. We took α/β = 10 Gy for HR-CTV, α/β = 3 Gy otherwise and half-time of repair 1.5 h.

Results

Without EBRT boost, ‘parameter adding’ yielded a good approximation. With an EBRT boost to lymph nodes, the total D90 HR-CTV was underestimated by 2.6 (SD 1.3)% for PDR and 2.8 (SD 1.4)% for HDR. This was even worse with a parametrium boost: 9.1 (SD 6.2)% for PDR and 9.9 (SD 6.2)% for HDR.

Conclusion

Without an EBRT boost ‘parameter adding’, as proposed by the GEC-ESTRO, yielded accurate results for the values for DVH parameters. If an EBRT boost is given ‘distributions adding’ should be considered.     

Limited benefit of inversely optimised intensity modulation in breast conserving radiotherapy with simultaneously integrated boost

Background and purpose

To examine whether in breast-conserving radiotherapy (RT) with simultaneously integrated boost (SIB), application of inversely planned intensity-modulated radiotherapy (IMRT-SIB) instead of three-dimensional RT (3D-CRT-SIB) has benefits that justify the additional costs, and to evaluate whether a potential benefit of IMRT-SIB depends on specific patient characteristics.

Material and methods

3D-CRT-SIB and various IMRT-SIB treatment plans were constructed and optimised for 30 patients with early stage left-sided breast cancer. Coverage of planning target volumes (PTVs) and dose delivered to organs at risk (OARs) were determined for each plan. Overlap between heart and breast PTV (OHB), size of breast and boost PTVs and boost location were examined in their ability to identify patients that might benefit from IMRT-SIB.

Results

All plans had adequate PTV coverage. IMRT-SIB generally reduced dose levels delivered to heart, lungs, and normal breast tissue relative to 3D-CRT-SIB. However, IMRT-SIB benefit differed per patient. For many patients, comparable results were obtained with 3D-CRT-SIB, while patients with OHB > 1.4 cm and a relatively large boost PTV volume (>125 cm³) gained most from the use of IMRT-SIB.

Conclusions

In breast-conserving RT, results obtained with 3D-CRT-SIB and IMRT-SIB are generally comparable. Patient characteristics could be used to identify patients that are most likely to benefit from IMRT-SIB.     

Bowel exposure in rectal cancer IMRT using prone, supine, or a belly board

Purpose

To investigate bowel exposure using prone, supine, or two different belly boards for rectal cancer intensity modulated RT plans using a full bladder protocol.

Methods and materials

For 11 volunteers four MR scans were acquired, on a flat table in prone, supine, and on two different belly boards (IT-V Medizintechnik GmbH® (BB1) and CIVCO® (BB2)), using a full bladder protocol. On each scan a 25 × 2 Gy IMRT plan was calculated.

Results

BB2 led to an average bowel area volume reduction of 20-30% at any dose level compared to prone. BB1 showed a smaller dose reduction effect, while no differences between prone and supine were found. Differences between BB2 and prone, supine or BB1 were significant up to a level of respectively, 45, 35, and 30 Gy. The reducing effect varied among individuals, except for the 50 Gy region, where no effect was found. An increase in bladder volume of 100 cc led to a significant bowel area V15 reduction of 16% independent of scan type.

Conclusions

In the low and intermediate dose region a belly board still attributes to a significant bowel dose reduction when using IMRT and a full bladder protocol. A larger bladder volume resulted in a significant decreased bowel area dose.     

Pathologic response rates following definitive dose image-guided chemoradiotherapy and resection for locally advanced non-small cell lung cancer

Introduction

Treatment of technically operable, medically fit locoregionally advanced non-small cell lung cancer (NSCLC) patients is a controversial therapeutic challenge. Our group routinely uses a trimodality approach. Recent advances in radiotherapy allow for improved tumor targeting and daily patient positioning. We hypothesized that these technologies would improve pathologic response rates. We analyzed consecutively treated stage IIIA/IIIB NSCLC patients undergoing chemoradiotherapy before major lung resection, with particular attention paid to the impact of advanced technologies.

Methods

Locoregionally advanced NSCLC patients (N2) staged in a multidisciplinary forum with mediastinoscopy were planned to receive platinum-based chemotherapy and 60 Gy and major lung resection. Four-dimensional CT (4DCT) and image-guided radiotherapy (IGRT) were used as available. Survival endpoints were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using Cox proportional hazards models.

Results

We identified 53 patients from 2/1999 to 2/2010. Median RT dose was 59 Gy. 68% underwent lobectomy. Forty-three patients were downstaged pathologically (81%), 38 experienced mediastinal sterilization (72%), and 21 (40%) had complete pathologic response (pCR). 1 and 2 year OS were 85.5% and 61.6%. Superior OS and DFS were associated with nodal downstaging and mediastinal sterilization (pN0). Treatment with IGRT/4DCT in 10 patients resulted in high rates of nodal downstaging (100% vs 77%, p = 0.0452), mediastinal sterilization (90% vs 67%, p = 0.0769), and pCR (60% vs 35%, p = 0.0728).

Conclusions

In selected patients, definitive dose CRT followed by major lung resection results in promising DFS and OS. The use of advanced radiotherapy techniques (4DCT and IGRT) appears to result in promising pathologic response rates.     

Endoglin haploinsufficiency reduces radiation-induced fibrosis and telangiectasia formation in mouse kidneys

Background and purpose

Endoglin is a transforming growth factor beta (TGF-β) co-receptor mainly expressed in dividing endothelial cells. It regulates cell proliferation and survival and is upregulated at sites of vessel repair. Mutations in endoglin have been linked to the vascular disease hereditary hemorrhagic telangiectasia (HHT). HHT patients display dilated capillaries (telangiectasia) that are prone to rupture. Cancer patients receiving radiotherapy develop similar vascular damage in normal tissues lying in the irradiation field. If located in the mucosa, irradiation-induced telangiectasia can lead to severe bleeding. Therefore, this study was aimed at investigating the role of endoglin in radiation-induced telangiectasia formation.

Materials and methods

Kidneys of endoglin heterozygous (Eng^+/−) or wild type mice were irradiated with 16 Gy. Mice were sacrificed after 20 weeks and changes in gene expression and protein levels were analysed.

Results

Expression of TGF-β target genes involved in radiation-induced fibrosis and fibrosis development in the kidney decreased in Eng^+/− compared to wild type mice. Unexpectedly, Eng^+/− mice also displayed reduced telangiectasia formation in the irradiated kidney.

Conclusions

Endoglin plays an important role in the development of irradiation-induced normal tissue damage. Future studies will show whether interfering with endoglin functions protects tissues from late radiation toxicity.     

Relative biological effectiveness of pulsed and continuous 20 MeV protons for micronucleus induction in 3D human reconstructed skin tissue

Background and purpose

Laser accelerated radiotherapy is a prospect for cancer treatment with proton and/or carbon ion beams that is currently under fast development. In principal, ultra fast, high-energy laser pulses will lead to a “pulsed” delivery of the induced ion beam with pulse durations of 1 ns and below, whereas conventional proton beams deriving from a cyclotron or synchrotron apply the dose within 100 ms (“continuous”).

Materials and methods

A simulation of both irradiation modes could be established at the Munich tandem accelerator with a 20 MeV proton beam, and a wide-field fast scanning system was implemented that allowed for application of up to 5 Gy per tissue voxel in a single pulse. The relative biological effectiveness (RBE) of pulsed and continuous modes of irradiation with 20 MeV protons relative to the reference radiation 70 kV X-rays was examined in a human tissue model (3D human reconstructed skin, EpiDermFT™) which preserves the three-dimensional geometric arrangement and communication of cells present in tissues in vivo. Using the induction of micronuclei (MN) in keratinocytes as the biological endpoint, the RBE was calculated as the ratio between the dose of 70 kV X-rays and 3 Gy of 20 MeV protons (pulsed or continuous) which produced equal response.

Results

For pulsed and continuous 20 MV proton exposures of the human skin model, RBE values of 1.08 ± 0.20 and 1.22 ± 0.15 versus 70 kV X-rays were obtained in a first experiment and 1.00 ± 0.14 and 1.13 ± 0.14 in a second experiment during distinct beam access times, respectively. The ∼10% difference in RBE between the respective irradiation modes in both experiments was associated with large uncertainties which were not statistically significant (p ≈ 0.5).

Conclusion

These findings represent an important step on the way towards application of laser-accelerated protons for clinical radiotherapy. Further clinically relevant endpoints in normal and tumor tissue have to be evaluated.     

Participation bias in a randomised trial of screening for lung cancer

Introduction

Participation bias might affect the results and the representability of randomised controlled trials. We investigated the degree of socio-demographic and psychosocial participation bias in the Danish Lung Cancer Screening Trial (DLCST).

Methods

In DLCST the questionnaire COS-LC (Consequences of Screening in Lung Cancer) was used to measure the psychosocial aspects of screening. To investigate a difference with a comparable representative sample from the Danish population, we sent out an inclusion questionnaire to 3999 Danes in the age from 50 to 70 years randomly selected from the Central National Register. Those who completed the inclusion questionnaire and met the inclusion criteria from DLCST received the COS-LC. Those who completed the COS-LC-and thus formed a population sample comparable to DLCST - were compared to the DLCST participants on socio-demographics and psychosocial measures.

Results

Participation rates were high among the comparable population sample: 75.3% completed the inclusion questionnaire and 77.4% of those who were eligible completed the COS-LC. The analyses revealed differences between the DLCST participants and the comparable population sample in the following socio-demographic aspects: social group, living alone, gender, age and geographical area. DLCST participants reported less negative psychosocial aspects than the comparable population sample.

Conclusion

The present study has shown substantial socio-demographic and psychosocial participation bias in DLCST.     

Effects of genistein following fractionated lung irradiation in mice

Background and purpose

This study investigated protection of lung injury by genistein following fractionated doses of radiation and its effect on tumor response.

Material and methods

C3H/HeJ mice were irradiated (100 kVp X-rays) with 9 fractions of 3.1 Gy over 30 days (approximately equivalent to 10 Gy single dose) and were maintained on a genistein diet (∼10 mg/kg). Damage was assessed over 28 weeks in lung cells by a cytokinesis block micronucleus (MN) assay and by changes in breathing rate and histology. Tumor protection was assessed using a colony assay to determine cell survival following in situ irradiation of small lung nodules (KHT fibrosarcoma).

Results

Genistein caused about a 50% reduction in the MN damage observed during the fractionated radiation treatment and this damage continued to decrease at later times to background levels by 16 weeks. In mice not receiving Genistein MN levels remained well above background out to 28 weeks after irradiation. Genistein reduced macrophage accumulation by 22% and reduced collagen deposition by 28%. There was minimal protection against increases in breathing rate or severe morbidity during pneumonitis. No tumor protection by genistein treatment was observed.

Conclusions

Genistein at the dose levels used in this study partially reduced the extent of fibrosis developing in mouse lung caused by irradiation but gave minimal protection against pneumonitis. There was no evidence that genistein caused protection of small tumors growing in the lung.     

Treatment delivery time optimization of respiratory gated radiation therapy by application of audio-visual feedback

Purpose

The feasibility to use visually guided voluntary breath-hold with and without audio assistance to reduce the total treatment time was evaluated.

Materials and methods

Patients referred for gated SBRT received hypofractionation schedules for lung or liver treatments. The patients were treated with the Novalis^® system (BrainLAB AG, Feldkirchen, Germany) and IGRT was performed with ExacTrac5.0/NovalisBody^® allowing gated irradiation. Video glasses, used for visual feedback to guide voluntary breath-hold, allowed additional audio assistance during treatment.The technique was applied for 25 patients of whom 9 were treated in free breathing, 7 had only visual feedback and another 9 had both audio and visual feedback.

Results

The delivery time of gated treatment during free breathing had an average value of 1.7 min/100 MU (SD 0.6 min/100 MU). The introduction of visual feedback reduced the average delivery time to 1.4 min/100 MU (SD 0.4 min/100 MU). The treatments with additional audio assistance indicated a significant reduction (p = 0.004) of the average delivery time to 0.9 min/100 MU (SD 0.2 min/100 MU).

Conclusion

The introduction of visually guided voluntary breath-hold with audio assistance led to treatment times for gated radiation therapy approaching conformal beam delivery times, which made gated treatments applicable in conventional treatment time slots.