| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- Baumann, Pia
(author)
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Stereotactic body radiotherapy in non-small cell lung cancer
- 2009
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Doctoral thesis (other academic/artistic)abstract
- Patients with stage I non small cell lung cancer (NSCLC) are potentially curable. Eradication of the primary tumour is a prerequisite for cure with surgery as standard treatment. A large part of NSCLC patients, in parallel to their cancer, also suffer from other smoke related diseases like chronic obstructive pulmonary disease (COPD) and cardio vascular diseases (CVD). In about 15 % of the patients with stage I NSCLC these coexisting diseases confer inoperability. With conventionally fractionated radiotherapy (CFRT) local tumour control is obtained in less than 50% of stage I NSCLC patients. This is related to limitations in permissive dose mainly due to risk of unacceptable toxicity in surrounding normal lung parenchyma. With stereotactic body radiotherapy (SBRT) doses high enough to sterilize the tumour, without excessive toxicity in normal tissue, can be delivered. The aim of this doctoral thesis and the underlying papers has mainly been to collect clinical evidence for a role of SBRT in the treatment of NSCLC. In the thesis, outcome and toxicity were analyzed in a retrospective and a prospective study on stage I NSCLC in altogether 195 patients treated with SBRT. COPD or CVD was the main reason for inoperability among the patients. The total radiation doses given had a median peripheral biologic effective dose (BED10) of 113 Gy and a central dose of 211Gy. Median follow up was 3 years. Local tumour control rate was 88% in the retrospective (ret.) and 92% in the prospective (pro.) study. Only 5% (pro.) and 7% (ret.) of the patients experienced regional failure. During follow up, distant metastases were recorded in 16% (pro.) and 25% (ret.) of the patients. Overall survival at 3-years was 52% (ret.) and 60% (pro.) but lung cancer specific survival was 66% (ret.) and 88% (pro.), a difference that likely is explained by death due to co-morbidity. To further develop SBRT a better understanding of the risk of toxicity is needed. This is especially important in patients with COPD who already have an impaired lung capacity. On the whole, toxicity after SBRT was mild and in 59% (ret.) and 21% (pro.) of the patients no side-effects were recorded. Objective lung function measured as forced expiratory volume in 1 second (FEV1%) did not decrease more than what is expected in a non-irradiated patient cohort, during the follow-up period. Clinically important toxicity was seen in 10% (ret.) and 30% (pro.) where dyspnoea and thoracic pain were most common. No significant difference was seen between COPD and CVD patients. Notable is that COPD patients with the poorest lung function tolerated SBRT to the same extent as other patients. In SBRT of lung tumours no established relationship between dose-volume parameters and the incidence of clinical radiation pneumonitis (RP2+) has been shown which is contradictory to the situation with conventionally fractionated radiotherapy (CFRT). Dose-volume-histogram (DVH) and toxicity data from the prospective study was used for normal tissue complication probability (NTCP) modelling. DVH data was corrected to 2 Gy/fraction using the universal survival curve (USC) model as well as the LQ model with á/â of 3 Gy and 20 Gy. In SBRT of lung tumours NTCP modelling with USC used for fractionation correction, resulted in a more serial architecture of functional subunits in the lung than what is seen after CFRT. In conclusion, SBRT for early stage lung cancer provides local control rates similar to what is obtained with surgery. SBRT is also well tolerated with only limited side-effects even in patients with markedly decreased pulmonary function. The calculated risk of pneumonitis, using the models in this study, depended relatively more on the volume with the highest doses than what is seen after CFRT. Overall survival is favourable compared to other nonsurgical treatments and lung cancer specific survival is excellent and with these results it is reasonable to conclude that SBRT should be offered to medically inoperable patients with stage I NSCLC.
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| 5. |
- 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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| 6. |
- Karlsson, Kristin, et al.
(author)
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Retrospective Cohort Study of Bronchial Doses and Radiation-Induced Atelectasis After Stereotactic Body Radiation Therapy of Lung Tumors Located Close to the Bronchial Tree
- 2013
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In: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 87:3, s. 590-595
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Journal article (peer-reviewed)abstract
- Purpose: To evaluate the dose-response relationship between radiation-induced atelectasis after stereotactic body radiation therapy (SBRT) and bronchial dose. Methods and Materials: Seventy-four patients treated with SBRT for tumors close to main, lobar, or segmental bronchi were selected. The association between incidence of atelectasis and bronchial dose parameters (maximum point-dose and minimum dose to the high-dose bronchial volume [ranging from 0.1 cm(3) up to 2.0 cm(3)]) was statistically evaluated with survival analysis models. Results: Prescribed doses varied between 4 and 20 Gy per fraction in 2-5 fractions. Eighteen patients (24.3%) developed atelectasis considered to be radiation-induced. Statistical analysis showed a significant correlation between the incidence of radiation-induced atelectasis and minimum dose to the high-dose bronchial volumes, of which 0.1 cm(3) (D-0.1cm3) was used for further analysis. The median value of D-0.1cm3 (alpha/beta = 3 Gy) was EQD(2,LQ) = 147 Gy(3) (range, 20-293 Gy(3)). For patients who developed atelectasis the median value was EQD(2,LQ) = 210 Gy(3), and for patients who did not develop atelectasis, EQD(2,LQ) = 105 Gy(3). Median time from treatment to development of atelectasis was 8.0 months (range, 1.1-30.1 months). Conclusion: In this retrospective study a significant dose-response relationship between the incidence of atelectasis and the dose to the high-dose volume of the bronchi is shown.
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| 7. |
- Wennberg, Berit M., et al.
(author)
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NTCP modelling of lung toxicity after SBRT comparing the universal survival curve and the linear quadratic model for fractionation correction
- 2011
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In: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 50:4, s. 518-527
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Journal article (peer-reviewed)abstract
- Background. In SBRT of lung tumours no established relationship between dose-volume parameters and the incidence of lung toxicity is found. The aim of this study is to compare the LQ model and the universal survival curve (USC) to calculate biologically equivalent doses in SBRT to see if this will improve knowledge on this relationship. Material and methods. Toxicity data on radiation pneumonitis grade 2 or more (RP2+) from 57 patients were used, 10.5% were diagnosed with RP2+. The lung DVHs were corrected for fractionation (LQ and USC) and analysed with the Lyman-Kutcher-Burman (LKB) model. In the LQ-correction alpha/beta = 3 Gy was used and the USC parameters used were: alpha/beta = 3 Gy, D-0 = 1.0 Gy, (n) over bar = 10, alpha = 0.206 Gy(-1) and d(T) = 5.8 Gy. In order to understand the relative contribution of different dose levels to the calculated NTCP the concept of fractional NTCP was used. This might give an insight to the questions of whether "high doses to small volumes" or "low doses to large volumes" are most important for lung toxicity. Results and Discussion. NTCP analysis with the LKB-model using parameters m = 0.4, D-50 = 30 Gy resulted for the volume dependence parameter (n) with LQ correction n = 0.87 and with USC correction n = 0.71. Using parameters m = 0.3, D-50 = 20 Gy n = 0.93 with LQ correction and n = 0.83 with USC correction. In SBRT of lung tumours, NTCP modelling of lung toxicity comparing models (LQ, USC) for fractionation correction, shows that low dose contribute less and high dose more to the NTCP when using the USC-model. Comparing NTCP modelling of SBRT data and data from breast cancer, lung cancer and whole lung irradiation implies that the response of the lung is treatment specific. More data are however needed in order to have a more reliable modelling.
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