[show abstract][hide abstract] ABSTRACT: Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated with daily image-guided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa).
A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1-2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5-7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT.
The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p < 0.001). For GU toxicity the numbers were 41.8% and 29.7%, respectively (p = 0.011). On multivariate analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p < 0.001, HR = 11.59 [CI: 6.67-20.14]). 3DCRT was also associated with an increased risk of developing GU toxicity compared to IG-IMRT. The 3-year actuarial biochemical progression-free survival probability was 86.0% for 3DCRT and 90.3% for IG-IMRT (p = 0.386). On multivariate analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT.
The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction.
[show abstract][hide abstract] ABSTRACT: To present a novel tool that allows quantitative estimation and visualization of the risk of various relevant normal tissue endpoints to aid in treatment plan comparison and clinical decision making in radiation therapy (RT) planning for Hodgkin lymphoma (HL).
A decision-support tool for risk-based, individualized treatment plan comparison is presented. The tool displays dose-response relationships, derived from published clinical data, for a number of relevant side effects and thereby provides direct visualization of the trade-off between these endpoints. The Quantitative Analyses of Normal Tissue Effects in the Clinic reports were applied, complemented with newer data where available. A "relevance score" was assigned to each data source, reflecting how relevant the input data are to current RT for HL.
The tool is applied to visualize the local steepness of dose-response curves to drive the reoptimization of a volumetric modulated arc therapy treatment plan for an HL patient with head-and-neck involvement. We also use this decision-support tool to visualize and quantitatively evaluate the trade-off between a 3-dimensional conformal RT plan and a volumetric modulated arc therapy plan for a patient with mediastinal HL.
This multiple-endpoint decision-support tool provides quantitative risk estimates to supplement the clinical judgment of the radiation oncologist when comparing different RT options.
International journal of radiation oncology, biology, physics 12/2013; · 4.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate dose plans for head and neck organs at risk (OARs) for classical Hodgkin lymphoma (HL) patients using involved node radiotherapy (INRT) delivered as 3D conformal radiotherapy (3DCRT), volumetric modulated arc therapy (VMAT), and intensity modulated proton therapy (PT), in comparison to the past mantle field (MF).
Data from 37 patients with cervical lymph node involvement were used. All patients originally received chemotherapy followed by 3DCRT-INRT (30.6Gy). A VMAT-INRT, PT-INRT (both 30.6Gy), and a MF plan (36Gy) were simulated. Doses to head and neck OARs were compared with cumulative DVHs and repeated measures ANOVA.
The estimated median mean doses were 15.3, 19.3, 15.4, and 37.3Gy (thyroid), 10.9, 12.0, 7.9, and 34.5Gy (neck muscles), 2.3, 11.1, 1.8, and 37.1Gy (larynx), 1.7, 5.1, 1.3, and 23.8Gy (pharynx), 0.5, 0.8, 0.01, and 32.3Gy (ipsilateral parotid), and 2.4, 3.8, 0.7, and 34.7Gy (ipsilateral submandibular) with 3DCRT, VMAT, PT, and MF (all p<0.0001), respectively.
The use of INRT significantly lowered the estimated radiation dose to the head and neck OARs. VMAT appeared suboptimal compared to 3DCRT and PT, and for some patients, PT offered an additional gain.
Radiotherapy and Oncology 11/2013; · 4.52 Impact Factor
[show abstract][hide abstract] ABSTRACT: Abstract Introduction. The cure rate of early stage Hodgkin's lymphoma (HL) is excellent; investigating the late effects of treatment is thus important. Esophageal toxicity is a known side effect in patients receiving radiotherapy (RT) to the mediastinum, although little is known of this in HL survivors. This study investigates the dose to the esophagus in the treatment of early stage HL using different RT techniques. Estimated risks of early esophagitis, esophageal stricture and cancer are compared between treatments. Material and methods. We included 46 patients ≥ 15 years with supradiaphragmatic, clinical stage I-II HL, who received chemotherapy followed by involved node RT (INRT) to 30.6 Gy at our institution. INRT was planned with three-dimensional conformal RT (3DCRT). For each patient a volumetric modulated arc therapy (VMAT), proton therapy (PT) and mantle field (MF) treatment plan was simulated. Mean, maximum and minimum dose to the esophagus were extracted from the treatment plans. Risk estimates were based on dose-response models from clinical series with long-term follow-up. Statistical analyses were performed with repeated measures ANOVA using Bonferroni corrections. Results. Mean dose to the esophagus was 16.4, 16.4, 14.7 and 34.2 Gy (p < 0.001) with 3DCRT, VMAT, PT and MF treatment, respectively. No differences were seen in the estimated risk of developing esophagitis, stricture or cancer with 3DCRT compared to VMAT (p = 1.000, p = 1.000, p = 0.356). PT performed significantly better with the lowest risk estimates on all parameters compared to the photon treatments, except compared to 3DCRT for stricture (p = 0.066). On all parameters the modern techniques were superior to MF treatment (p < 0.001). Conclusions. The estimated dose to the esophagus and the corresponding estimated risks of esophageal complications are decreased significantly with highly conformal RT compared to MF treatment. The number of patients presenting with late esophageal side effects will, thus, likely be minimal in the future.
[show abstract][hide abstract] ABSTRACT: Hodgkin lymphoma (HL) survivors are at an increased risk of stroke because of carotid artery irradiation. However, for early-stage HL involved node radiation therapy (INRT) reduces the volume of normal tissue exposed to high doses. Here, we evaluate 3-dimensional conformal radiation therapy (3D-CRT), volumetric-modulated arc therapy (VMAT), and proton therapy (PT) delivered as INRT along with the extensive mantle field (MF) by comparing doses to the carotid arteries and corresponding risk estimates.
We included a cohort of 46 supradiaphragmatic stage I-II classical HL patients. All patients were initially treated with chemotherapy and INRT delivered as 3D-CRT (30 Gy). For each patient, we simulated MF (36 Gy) and INRT plans using VMAT and PT (30 Gy). Linear dose-response curves for the 20-, 25-, and 30-year risk of stroke were derived from published HL data. Risks of stroke with each technique were calculated for all patients. Statistical analyses were performed with repeated measures analysis of variance.
The mean doses to the right and left common carotid artery were significantly lower with modern treatment compared with MF, with substantial patient variability. The estimated excess risk of stroke after 20, 25, and 30 years was 0.6%, 0.86%, and 1.3% for 3D-CRT; 0.67%, 0.96%, and 1.47% for VMAT; 0.61%, 0.96%, and 1.33% for PT; and 1.3%, 1.72%, and 2.61% for MF.
INRT reduces the dose delivered to the carotid arteries and corresponding estimated risk of stroke for HL survivors. Even for the subset of patients with lymphoma close to the carotid arteries, the estimated risk is low.
International journal of radiation oncology, biology, physics 08/2013; · 4.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background:Adrenocortical carcinoma (ACC) is a rare disease with a poor response to chemotherapy. Cisplatin is the most widely investigated drug in the treatment of ACC and in vitro studies have indicated activity of taxanes. The objectives of this study were to evaluate the efficacy and toxicity of cisplatin combined with docetaxel as first-line treatment of advanced ACC.Methods:Patients with advanced ACC were included in this phase II trial investigating the response to a combination of cisplatin (50 mg m(-2)) and docetaxel (60 mg m(-2)) administered with a 3-week interval.Results:Nineteen patients were included in this study. The response rate was 21% (95% CI: 3-39%). No patients obtained a complete response, 32% had stable disease, and 37% progressed while on treatment. The median progression-free survival (PFS) was 3 months (95% CI: 0.7-5.3 months) and 1 year PFS was 21% (95% CI: 3-39%). Median survival was 12.5 months (95% CI: 6-19 months). The predominant grade 3/4 toxicity was neutropenia (35%); febrile neutropenia occurred in 5% of cycles.Conclusion:This study could not demonstrate that the combination of cisplatin and docetaxel has higher efficacy than other regimens reported in previous studies.British Journal of Cancer advance online publication, 7 May 2013; doi:10.1038/bjc.2013.229 www.bjcancer.com.
British Journal of Cancer 05/2013; · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background
Hodgkin lymphoma (HL) survivors have an increased morbidity and mortality from secondary cancers and cardiovascular disease (CD). We evaluate doses with involved node radiotherapy (INRT) delivered as 3D conformal radiotherapy (3D CRT), volumetric modulated arc therapy (VMAT), or proton therapy (PT), compared with the extensive Mantle Field (MF).Patients and methodsFor 27 patients with early-stage, mediastinal HL, treated with chemotherapy and INRT delivered as 3D CRT (30 Gy), we simulated an MF (36 Gy), INRT-VMAT and INRT-PT (30 Gy). Dose to the heart, lungs, and breasts, estimated risks of CD, lung (LC) and breast cancer (BC), and corresponding life years lost (LYL) were compared.Results3D CRT, VMAT or PT significantly lower the dose to the heart, lungs and breasts and provide lower risk estimates compared with MF, but with substantial patient variability. The risk of CD is not significantly different for 3D CRT versus VMAT. The risk of LC and BC is highest with VMAT. For LYL, PT is the superior modern technique.Conclusions
In early-stage, mediastinal HL modern radiotherapy provides superior results compared with MF. However, there is no single best radiotherapy technique for HL-the decision should be made at the individual patient level.
[show abstract][hide abstract] ABSTRACT: Adrenocortical carcinomas (ACC) are rare tumours responsible for only 0.02% of the total number of malignant diseases. However the ACC are aggressive with a mean fiveyears survival of 20-50% and are often associated with increased production of adrenocortical hormones. The effect of the treatment is controversial and often based on small retrospective series or expert opinions. Centralization, international attention and collaboration in the treatment of ACC are mandatory. Randomized clinical trials are needed to determine the best treatment strategy in order to increase survival in patients with ACC.
[show abstract][hide abstract] ABSTRACT: This study investigated the dosimetric impact of uncompensated motion and motion compensation with dynamic multileaf collimator (DMLC) tracking for prostate intensity modulated arc therapy. Two treatment approaches were investigated; a conventional approach with a uniform radiation dose to the target volume and an intraprostatic lesion (IPL) boosted approach with an increased dose to a subvolume of the prostate. The impact on plan quality of optimizations with a leaf position constraint, which limited the distance between neighbouring adjacent MLC leaves, was also investigated. Deliveries were done with and without DMLC tracking on a linear acceleration with a high-resolution MLC. A cylindrical phantom containing two orthogonal diode arrays was used for dosimetry. A motion platform reproduced six patient-derived prostate motion traces, with the average displacement ranging from 1.0 to 8.9 mm during the first 75 s. A research DMLC tracking system was used for real-time motion compensation with optical monitoring for position input. The gamma index was used for evaluation, with measurements with a static phantom or the planned dose as reference, using 2% and 2 mm gamma criteria. The average pass rate with DMLC tracking was 99.9% (range 98.7-100%, measurement as reference), whereas the pass rate for untracked deliveries decreased distinctly as the average displacement increased, with an average pass rate of 61.3% (range 32.7-99.3%). Dose-volume histograms showed that DMLC tracking maintained the planned dose distributions in the presence of motion whereas traces with >3 mm average displacement caused clear plan degradation for untracked deliveries. The dose to the rectum and bladder had an evident dependence on the motion direction and amplitude for untracked deliveries, and the dose to the rectum was slightly increased for IPL boosted plans compared to conventional plans for anterior motion with large amplitude. In conclusion, optimization using a leaf position constraint had minimal dosimetric effect, DMLC tracking improved the target and normal tissue dose distributions compared to no tracking for target motion >3 mm, with the DMLC tracking distributions showing generally good agreement between the planned and delivered doses.
Physics in Medicine and Biology 03/2013; 58(7):2349-2361. · 2.70 Impact Factor
[show abstract][hide abstract] ABSTRACT: Thymomas are the most frequently occurring tumours of the anterior mediastinum. However, they only constitue less than 1% of the total number of malignant diseases. The incidence in the USA is 0.15 per 100.000 persons per year, and the disease is most frequent in persons between 40 and 60 years of age. Because of the rarity of thymomas, lack of uniformity in treatment has been a major problem over the years. Therefore, international collaborations have been established, and national oncological centralisation of management has been arranged in order to improve the treatment and prognosis.
[show abstract][hide abstract] ABSTRACT: PURPOSE: The involved node radiation therapy (INRT) strategy was introduced for patients with Hodgkin lymphoma (HL) to reduce the risk of late effects. With INRT, only the originally involved lymph nodes are irradiated. We present treatment outcome in a retrospective analysis using this strategy in a cohort of 97 clinical stage I-II HL patients. METHODS AND MATERIALS: Patients were staged with positron emission tomography/computed tomography scans, treated with adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy, and given INRT (prechemotherapy involved nodes to 30 Gy, residual masses to 36 Gy). Patients attended regular follow-up visits until 5 years after therapy. RESULTS: The 4-year freedom from disease progression was 96.4% (95% confidence interval: 92.4%-100.4%), median follow-up of 50 months (range: 4-71 months). Three relapses occurred: 2 within the previous radiation field, and 1 in a previously uninvolved region. The 4-year overall survival was 94% (95% confidence interval: 88.8%-99.1%), median follow-up of 58 months (range: 4-91 months). Early radiation therapy toxicity was limited to grade 1 (23.4%) and grade 2 (13.8%). During follow-up, 8 patients died, none from HL, 7 malignancies were diagnosed, and 5 patients developed heart disease. CONCLUSIONS: INRT offers excellent tumor control and represents an effective alternative to more extended radiation therapy in the combined modality treatment for early-stage HL.
International journal of radiation oncology, biology, physics 11/2012; · 4.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: We report 3 cases of patients with testicular cancer and stage II seminoma who developed neurological symptoms with bilateral leg weakness about 4 to 9 months after radiation therapy (RT). They all received RT to the para-aortic lymph nodes with a total dose of 40 Gy (36 Gy + 4 Gy as a boost against the tumour bed) with a conventional fractionation of 2 Gy/day, 5 days per week. RT was applied as hockey-stick portals, also called L-fields. In 2 cases, the symptoms fully resolved. Therapeutic irradiation can cause significant injury to the peripheral nerves of the lumbosacral plexus and/or to the spinal cord. RT is believed to produce plexus injury by both direct toxic effects and secondary microinfarction of the nerves, but the exact pathophysiology of RT-induced injury is unclear. Since reported studies of radiation-induced neurological adverse effects are limited, it is difficult to estimate their frequency and outcome. The treatment of neurological symptoms due to RT is symptomatic.
[show abstract][hide abstract] ABSTRACT: Hodgkin lymphoma (HL) survivors are known to have increased cardiac mortality and morbidity. The risk of developing cardiovascular disease after involved node radiotherapy (INRT) is currently unresolved, inasmuch as present clinical data are derived from patients treated with the outdated mantle field (MF) technique.
We included all adolescents and young adults with supradiaphragmatic, clinical Stage I-II HL treated at our institution from 2006 to 2010 (29 patients). All patients were treated with chemotherapy and INRT to 30 to 36 Gy. We then simulated a MF plan for each patient with a prescribed dose of 36 Gy. A logistic dose-response curve for the 25-year absolute excess risk of cardiovascular disease was derived and applied to each patient using the individual dose-volume histograms.
The mean doses to the heart, four heart valves, and coronary arteries were significantly lower for INRT than for MF treatment. However, the range in doses with INRT treatment was substantial, and for a subgroup of patients, with lymphoma below the fourth thoracic vertebrae, we estimated a 25-year absolute excess risk of any cardiac event of as much as 5.1%.
Our study demonstrates a potential for individualizing treatment by selecting the patients for whom INRT provides sufficient cardiac protection for current technology; and a subgroup of patients, who still receive high cardiac doses, who would benefit from more advanced radiation technique.
International journal of radiation oncology, biology, physics 01/2012; 83(4):1232-7. · 4.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: Total skin electron beam therapy (TSEBT) is a powerful treatment for cutaneous T-cell lymphoma (CTCL). Based on the occurrence of relapses with low radiation doses, doses of 30-36Gy are commonly used but most patients still eventually relapse and repeat treatment courses are limited due to the cumulative toxicity. Complete response (CR) rates are about 60-90% for T2-4 stages with a 5-year relapse-free survival of 10-25% for stages IB-III.
To evaluate prospectively the efficacy of low-dose TSEBT (10Gy) in terms of complete cutaneous response rate, overall response rate and response duration in CTCL.
Ten patients with stage IB-IV mycosis fungoides (MF) were treated in an open-label manner with four fractions of TSEBT 1Gy weekly to a total skin dose of 10Gy. Treatment responses were assessed at 1 and 3months after treatment and subsequently at least every 6months for a total period of 2years or to disease relapse or progression.
Patients achieved an overall response rate of 90%. The rate of CR or very good partial response (VGPR; <1% skin affected with patches/plaques) was 70%. The median response duration was 5·2months (range 83-469days) for CR and VGPR. Adverse effects were generally mild to moderate in severity.
Low-dose TSEBT (10Gy) gave a satisfactory response rate and was well tolerated in patients with MF stage IB-IV. Future studies should determine if the combination of low-dose TSEBT with other agents could increase the rate of CR and response duration.
British Journal of Dermatology 10/2011; 166(2):399-404. · 3.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: Total skin electron beam therapy (TSEBT) is an effective palliative treatment for cutaneous T-cell lymphoma (CTCL). In the present study we reviewed the clinical response to TSEBT in Danish patients with CTCL.
This retrospective study included 35 patients with CTCL treated with TSEBT in Denmark from 2001 to 2008 and followed for a median time of 7.6 months (range 3 days-3.7 years). Twenty five patients were treated with high-dose (30 Gy) and 10 patients in a protocol with low-dose (4 Gy) TSEBT.
Patients treated with low-dose therapy had inadequate response to treatment compared to patients treated with high-dose. Consequently the study with low-dose was discontinued and published. In patients treated with high-dose the overall response rate was 100%. Complete response (CR) rate was 68% and CR occurred after a median time of 2.1 months (range 1.8 months-2.0 years). We found no difference in CR rate in patients with T2 (66.7%) and T3 disease (78.6%) (p = 0.64). Following CR 82.4% relapsed at a median time of four months (range 12 days-11.5 months). Relapse-free-survival was similar in patients with T2 and T3 disease (p = 0.77). Progressive disease (PD) was experienced in 28.0% and the median time to PD was 9.0 months (range 4.6-44.3 months). Overall progression-free survival was 95.3%, 72.1% and 64.1% after 0.5-, 1- and 2-years. Effects of initial therapy on TSEBT treatment response and side effects to TSEBT were also analyzed.
In conclusion, the present study confirms that high-dose TSEBT is an effective, but generally not a curative therapy in the management of CTCL. High-dose treatment yielded significantly better results than low-dose treatment with 4 Gy. TSEBT offers significant palliation in most patients when other skin-directed or systemic treatments have failed.
[show abstract][hide abstract] ABSTRACT: A systematic overview and meta-analysis of studies reporting data on hypothyroidism (HT) after radiation therapy was conducted to identify risk factors for development of HT.
Published studies were identified from the PubMed and Embase databases and by hand-searching published reviews. Studies allowing the extraction of odds ratios (OR) for HT in 1 or more of several candidate clinical risk groups were included. A meta-analysis of the OR for development of HT with or without each of the candidate risk factors was performed. Furthermore, studies allowing the extraction of radiation dose-response data were identified for a meta-analysis of the dose-response curve.
Female gender (OR = 1.6; 95% confidence interval [CI], 1.3-1.9; P < .00001), surgery involving the thyroid gland (OR = 8.3; 95% CI, 5.7-12.0; P < .00001), or other neck surgery (OR = 1.7; 95% CI, 1.16-2.42; P = .006) were associated with a higher risk of HT. Caucasians were at higher risk of HT than African Americans (OR = 4.8; 95% CI, 2.8-8.5; P < .00001). The data showed association between lymphangiography and HT but with evidence of publication bias. There was a radiation dose-response relation with a 50% risk of HT at a dose of 45 Gy but with considerable variation in the dose response between studies. Chemotherapy and age were not associated with risk of HT in this analysis.
Several clinical risk factors for HT were identified. The risk of HT increases with increasing radiation dose, but the specific radiation dose response varies between the studies. The most likely cause of this heterogeneity is differences in follow-up between studies.
Cancer 05/2011; 117(23):5250-60. · 5.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: Positional uncertainties related to the set-up of the prostate, using internal markers and either 2D-2D or 3D images, were studied. Set-up using direct prostate localization on CBCT scans is compared to set-up using internal markers.
20 patients with prostate cancer were enrolled in the study. After each daily session, a set of 2D-2D and 3D images were acquired. The images isocenter was compared to reference images isocenter. For the set-up error analysis the systematic error, μ, and the set-up uncertainties, Σ and σ, were determined for the translational shift in the three directions, lat, lng and vrt. The set-up errors and uncertainties were calculated in the same way for rotations around the three axes, lat, lng and vrt.
Set-up uncertainties were evaluated for four different set-up methods. The systematic error uncertainties were found to be in the range 0.38-1.14 mm and for the random error 0.79-1.48 mm. For rotations the uncertainties ranges were 0.38-1.59° and 0.91-2.18° for systematic and random uncertainties, respectively. Set-up uncertainties, using internal markers or prostate itself to position the target in the isocenter, were comparable. The correlation between the two methods was better for translational shifts of the isocenter than for rotational shifts.
The study shows that the precision of the 2D-2D set-up is equivalent to the precision of the 3D images. It also shows that the soft-tissue based set-up needs 1 mm larger set-up margins than the marker based set-up for the prostate patients, when CBCT is used for daily verification of the location of the prostate.
Radiotherapy and Oncology 02/2011; 98(2):175-80. · 4.52 Impact Factor