| 1. |
- Johansson, Karl-Axel, et al.
(author)
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The quality assurance process for the ARTSCAN head and neck study - a practical interactive approach for QA in 3DCRT and IMRT.
- 2008
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In: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 87:2, s. 290-9
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Journal article (peer-reviewed)abstract
- AIM: This paper describes the quality assurance (QA) work performed in the Swedish multicenter ARTSCAN (Accelerated RadioTherapy of Squamous cell CArcinomas in the head and Neck) trial to guarantee high quality in a multicenter study which involved modern radiotherapy such as 3DCRT or IMRT. MATERIALS AND METHODS: The study was closed in June 2006 with 750 randomised patients. Radiation therapy-related data for every patient were sent by each participating centre to the QA office where all trial data were reviewed, analysed and stored. In case of any deviation from the protocol, an interactive process was started between the QA office and the local responsible clinician and/or physicist to increase the compliance to the protocol for future randomised patients. Meetings and workshops were held on a regular basis for discussions on various trial-related issues and for the QA office to report on updated results. RESULTS AND DISCUSSION: This review covers the 734 patients out of a total of 750 who had entered the study. Deviations early in the study were corrected so that the overall compliance to the protocol was very high. There were only negligible variations in doses and dose distributions to target volumes for each specific site and stage. The quality of the treatments was high. Furthermore, an extensive database of treatment parameters was accumulated for future dose-volume vs. endpoint evaluations. CONCLUSIONS: This comprehensive QA programme increased the probability to draw firm conclusions from our study and may serve as a concept for QA work in future radiotherapy trials where comparatively small effects are searched for in a heterogeneous tumour population.
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| 2. |
- Baumann, Pia, et al.
(author)
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Factors important for efficacy of stereotactic body radiotherapy of medically inoperable stage I lung cancer. A retrospective analysis of patients treated in the Nordic countries.
- 2006
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In: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 45:7, s. 787-95
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Journal article (peer-reviewed)abstract
- We reviewed results of SBRT treatment of 138 patients with medically inoperable stage I NSCLC treated during 1996-2003 at five different centres in Sweden and Denmark. Mean age was 74 years (range 56-90) with 69 men and 72 women. SBRT was delivered using a 3D conformal multifield technique and a stereotactic body frame. Doses delivered were 30-48 Gy (65% isodose at the periphery of planning target volume, PTV) in 2-4 fractions. Equivalent dose in 2 Gy fractions (EQD2) was in the range of 50-100 Gy. Mean gross tumour volume (GTV) was 39 cm3 (2-436), and planning target volume was 101 cm3 (11-719). Overall response rate (CR, PR) was 61% (84/138). SD was noted in 36% (50/138). During a median follow-up period of 33 months (1-107), 16 (12%) local failures occurred, ten of which also included distant metastases. Local failure was associated with tumour size, target definition and central or pleura proximity. Distant metastases occurred in 25% (35/138) of the patients. Ninety-one (65%) patients died during follow-up of which 55 patients (60%) died of other causes than lung cancer. Three- and 5-year overall survival was 52 and 26% respectively. Lung cancer specific 3- and 5-year overall survival was 66 and 40% respectively. Fifty nine percent (83/138) of the patients had no side effects. Fourteen patients experienced grade 3-4 toxicity according to radiation therapy oncology group (RTOG). EQD2 (> v.s.<55.6 Gy) showed a statistically significant benefit survival for the higher doses. SBRT for stage I NSCLC results in favourable local control not inferior to fractionated RT and with acceptable toxicity.
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| 3. |
- Baumann, Pia, et al.
(author)
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Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated with stereotactic body radiotherapy.
- 2009
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In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755 .- 0732-183X. ; 27:20, s. 3290-6
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Journal article (peer-reviewed)abstract
- PURPOSE: The impact of stereotactic body radiotherapy (SBRT) on 3-year progression-free survival of medically inoperable patients with stage I non-small-cell lung cancer (NSCLC) was analyzed in a prospective phase II study. PATIENTS AND METHODS: Fifty-seven patients with T1NOMO (70%) and T2N0M0 (30%) were included between August 2003 and September 2005 at seven different centers in Sweden, Norway, and Denmark and observed up to 36 months. SBRT was delivered with 15 Gy times three at the 67% isodose of the planning target volume. RESULTS: Progression-free survival at 3 years was 52%. Overall- and cancer-specific survival at 1, 2, and 3 years was 86%, 65%, 60%, and 93%, 88%, 88%, respectively. There was no statistically significant difference in survival between patients with T1 or T2 tumors. At a median follow-up of 35 months (range, 4 to 47 months), 27 patients (47%) were deceased, seven as a result of lung cancer and 20 as a result of concurrent disease. Kaplan-Meier estimated local control at 3 years was 92%. Local relapse was observed in four patients (7%). Regional relapse was observed in three patients (5%). Nine patients (16%) developed distant metastases. The estimated risk of all failure (local, regional, or distant metastases) was increased in patients with T2 (41%) compared with those with T1 (18%) tumors (P = .027). CONCLUSION: With a 3-year local tumor control rate higher than 90% with limited toxicity, SBRT emerges as state-of-the-art treatment for medically inoperable stage I NSCLC and may even challenge surgery in operable instances.
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| 4. |
- Baumann, Pia, et al.
(author)
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Stereotactic body radiotherapy for medically inoperable patients with stage I non-small cell lung cancer - a first report of toxicity related to COPD/CVD in a non-randomized prospective phase II study.
- 2008
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In: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 88:3, s. 359-67
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: In a retrospective study using stereotactic body radiotherapy (SBRT) in medically inoperable patients with stage I NSCLC we previously reported a local control rate of 88% utilizing a median dose of 15Gyx3. This report records the toxicity encountered in a prospective phase II trial, and its relation to coexisting chronic obstructive pulmonary disease (COPD) and cardio vascular disease (CVD). MATERIAL AND METHODS: Sixty patients were entered in the study between August 2003 and September 2005. Fifty-seven patients (T1 65%, T2 35%) with a median age of 75 years (59-87 years) were evaluable. The baseline mean FEV1% was 64% and median Karnofsky index was 80. A total dose of 45Gy was delivered in three fractions at the 67% isodose of the PTV. Clinical, pulmonary and radiological evaluations were made at 6 weeks, 3, 6, 9, 12, 18, and 36 months post-SBRT. Toxicity was graded according to CTC v2.0 and performance status was graded according to the Karnofsky scale. RESULTS: At a median follow-up of 23 months, 2 patients had relapsed locally. No grade 4 or 5 toxicity was reported. Grade 3 toxicity was seen in 12 patients (21%). There was no significant decline of FEV1% during follow-up. Low grade pneumonitis developed to the same extent in the CVD 3/17 (18%) and COPD 7/40 (18%) groups. The incidence of fibrosis was 9/17 (53%) and pleural effusions was 8/17 (47%) in the CVD group compared with 13/40 (33%) and 5/40 (13%) in the COPD group. CONCLUSION: SBRT for stage I NSCLC patients who are medically inoperable because of COPD and CVD results in a favourable local control rate with a low incidence of grade 3 and no grade 4 or 5 toxicity.
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| 5. |
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| 6. |
- Ceberg, Sofie, et al.
(author)
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Verification of dynamic radiotherapy: the potential for 3D dosimetry under respiratory-like motion using polymer gel.
- 2008
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In: Physics in Medicine and Biology. - 1361-6560. ; 53:20, s. 387-396
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Journal article (peer-reviewed)abstract
- Following the implementation of advanced treatment procedures in radiotherapy, there is a need for dynamic dose verification in 3D. Gel dosimetry could potentially be used for such measurements. However, recently published data show that certain types of gels have a dose rate and fractionation dependence. The aim of this study was to investigate the feasibility of using a polymer gel dosimeter for dose verification of dynamic radiotherapy. To investigate the influence of dose rate dependence during respiratory-like motion in and out of the beam, a respiration robot together with two types of gel systems (normoxic methacrylic acid gel (nMAG) and normoxic polyacrylamide gel (nPAG)) were used. Reference measurements were obtained using a linear diode array (LDA). Expected results, if there was no influence of the dose rate variation, were calculated by convolving the static irradiated gel data with the motion function controlling the robot. To investigate the fractionation dependence, the gels were irradiated using gated and ungated deliveries. Magnetic resonance imaging was used to evaluate the absorbed dose response of the gel. The measured gel data coincided well with the LDA data. Also, the calculated data agreed well with the measured dynamic gel data, i.e. no dose rate dependence due to motion was observed. The difference in the R2 response for the gels receiving ungated and gated, i.e. fractionated, deliveries was less than 1% for the nPAG and 4% for the nMAG, for absorbed doses up to 2 Gy. The maximum difference was 1.2% for the nPAG and 9% for the nMAG, which occurred at the highest given dose (4 Gy). The investigated gels were found to be feasible detectors for dose measurements under respiratory-like motion. For dose verification of dynamic RT involving gated delivery, e.g. breathing-adapted radiotherapy, relative absorbed dose evaluation should be used in order to minimize the effects of fractionated irradiation.
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| 7. |
- Djärv, Emma, et al.
(author)
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Dummy run for a phase II study of stereotactic body radiotherapy of T1-T2 N0M0 medical inoperable non-small cell lung cancer.
- 2006
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In: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 45:7, s. 973-7
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Journal article (peer-reviewed)abstract
- In forthcoming multicentre studies on stereotactic body radiotherapy (SBRT) compliance with volume and dose prescriptions will be mandatory to avoid unnecessary heterogeneity bias. To evaluate compliance in a multicentre setting we used two cases from an ongoing phase II study of SBRT of T1-T2N0M0 inoperable NSCLC in a dummy run oriented on volumes and doses. Six Scandinavian centres participated. Each centre received CT-scans covering the whole lung volumes of two patients with instructions to follow the study protocol when outlining tumour and target volumes, prescribing doses and creating dose plans. Volumes and doses of the 12 dose plans were evaluated according to the study protocol. For the two patients the GTV volume range was 24 to 39 cm3 and 26 to 41 cm3, respectively. The PTV volume range was 90 to 116 cm3, and 112 to 155 cm3, respectively. For all plans the margin between CTV and PTV in all directions followed in detail the protocol. The prescribed dose was for all centres 45 Gy/3 fractions (isocentre dose about 66 Gy). The mean GTV doses ranged from 63 to 67 Gy and from 63 to 68 Gy, respectively. The minimum doses for GTV were between 50-64 Gy and between 55-65 Gy, respectively. The dose distribution was conformed to PTV for 10 of 12 plans and 2 of 12 plans from one centre had sub-optimal dose distribution. Most of the volume and dose parameters for the participating centres showed fully acceptable compliance with the study protocol.
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| 8. |
- Ekberg, Lars, et al.
(author)
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What margins should be added to the clinical target volume in radiotherapy treatment planning for lung cancer?
- 1988
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In: Radiotherapy and Oncology. - 1879-0887. ; 48:1, s. 71-77
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Journal article (peer-reviewed)abstract
- BACKGROUND: The planning target volume in radiotherapy treatment planning takes into account both movements of the clinical target volume (CTV) and set-up deviations. MATERIALS AND METHODS: A group of patients who received radiotherapy for lung cancer were studied. In order to measure the CTV movements due to respiration and other internal organ motions, fluoroscopy was performed for 20 patients. To study the accuracy and reproducibility of patient and beam set-up, 553 electronic portal images from 20 patients were evaluated. Discrepancies between planned and actual field positions were measured and the systematic and random errors were identified. The combined effect of these geometrical variations was evaluated. RESULTS: The average CTV movement with quiet respiration was about 2.4 mm in the medio-lateral and dorso-ventral directions. Movement in the cranio-caudal direction was on average 3.9 mm with a range of 0-12 mm. The systematic set-up errors were on average 2.0 mm in the transversal plane and 3.0 mm in the cranio-caudal direction. The random errors can be described by their standard deviations of 3.2 and 2.6 mm. In this study, the combined effect of the two parameters (CTV movement and set-up deviations) varied between 7.5 and 10.3 mm in different anatomical directions. CONCLUSIONS: In our daily clinical routine, we use a margin of 11 mm in the transversal plane and 15 mm cranially and caudally, also taking into account other unquantified variations and uncertainties.
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| 9. |
- Johnson, Louis Banka, et al.
(author)
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Combination of pre-operative radiotherapy and surgery suppresses local accumulation of collagen and TGF-beta 1 in rats
- 2006
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In: Journal of Surgical Research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 133:2, s. 136-142
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Journal article (peer-reviewed)abstract
- Background. The systemic and local tissue repair responses of radiation in combination with surgery are still unclear. We have studied the effect of fractionated pre-operative radiotherapy with or without subsequent laparotomy on collagen accumulation using a rodent model. Materials and methods. Thirty-two male Sprague-Dawley rats were divided into four groups (eight rats per group): 1) sham radiation and sham laparotomy (control); 2) sham radiation and laparotomy; 3) radiation and sham laparotomy; and 4) radiation followed by laparotomy. Expanded polytetrafluoroethylene (ePTFE) tubes were implanted subcutaneously in the abdominal wall in the radiotherapy field and on the back outside the radiotherapy field day 0. The abdomen (3 cm x 4 cm) was irradiated day 3 (10 Gy) and again day 7 (10 Gy). On day 10, implants were extirpated, laparotomy undertaken in groups 2 and 4 and new ePTFE tubes implanted subcutaneously. The second implants were extirpated on day 20. Implants were analyzed for hydroxyproline, total protein and transforming growth factor-ss 1 (TGF-ss 1) levels. Results. On day 10, hydroxyproline (P < 0.05) and TGF-ss 1 (P < 0.001) were lower in ePTFE tubes in irra-diated compared with non-irradiated rats. On day 20, the abdominal ePTFE hydroxyproline remained low (P < 0.001) in animals subjected to laparotomy and pre-operative irradiation while hydroxyproline levels of rats subjected to irradiation only were similar to controls. The effects of radiation on hydroxyproline were confined to the irradiated abdominal area. There was a positive correlation between hydroxyproline and TGF-ss 1 levels in the abdominal wall implant day 20 (r = 0.53, P < 0.005). Conclusion. A clinically relevant fractionated radiation scheme reduced subcutaneous collagen accumulation pre-operatively and profoundly within the radiation field post-operatively after laparotomy, possibly because of lowered TGF ss 1 levels. (c) 2006 Elsevier Inc. All rights reserved.
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| 10. |
- Johnson, Louis Banka, et al.
(author)
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Radiation enteropathy and leucocyte-endothelial cell reactions in a refined small bowel model
- 2004
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In: BMC Surgery. - : Springer Science and Business Media LLC. - 1471-2482. ; 4
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Journal article (peer-reviewed)abstract
- BACKGROUND: Leucocyte recruitment and inflammation are key features of high dose radiation-induced tissue injury. The inflammatory response in the gut may be more pronounced following radiotherapy due to its high bacterial load in comparison to the response in other organs. We designed a model to enable us to study the effects of radiation on leucocyte-endothelium interactions and on intestinal microflora in the murine ileum. This model enables us to study specifically the local effects of radiation therapy. METHOD: A midline laparotomy was performed in male C57/Bl6 mice and a five-centimetre segment of ileum is irradiated using the chamber. Leucocyte responses (rolling and adhesion) were then analysed in ileal venules 2 - 48 hours after high dose irradiation, made possible by an inverted approach using intravital fluorescence microscopy. Furthermore, intestinal microflora, myeloperoxidase (MPO) and cell histology were analysed. RESULTS: The highest and most reproducible increase in leucocyte rolling was exhibited 2 hours after high dose irradiation whereas leucocyte adhesion was greatest after 16 hours. Radiation reduced the intestinal microflora count compared to sham animals with a significant decrease in the aerobic count after 2 hours of radiation. Further, the total aerobic counts, Enterobacteriaceae and Lactobacillus decreased significantly after 16 hours. In the radiation groups, the bacterial count showed a progressive increase from 2 to 24 hours after radiation. CONCLUSION: This study presents a refinement of a previous method of examining mechanisms of radiation enteropathy, and a new approach at investigating radiation induced leucocyte responses in the ileal microcirculation. Radiation induced maximum leucocyte rolling at 2 hours and adhesion peaked at 16 hours. It also reduces the microflora count, which then starts to increase steadily afterwards. This model may be instrumental in developing strategies against pathological recruitment of leucocytes and changes in intestinal microflora in the small bowel after radiotherapy.
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