| 1. |
- Baumann, Pia, et al.
(författare)
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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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Ingår i: 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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Tidskriftsartikel (refereegranskat)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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| 2. |
- Baumann, Pia, et al.
(författare)
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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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Ingår i: 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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Tidskriftsartikel (refereegranskat)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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| 3. |
- Goldman, Ulla Blom, et al.
(författare)
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Long-term functional and radiological pulmonary changes after radiation therapy for breast cancer
- 2014
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 53:10, s. 1373-1379
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Tidskriftsartikel (refereegranskat)abstract
- Background. We assessed late functional and radiological pulmonary changes in breast cancer patients after a median of 11 years following radiotherapy (RT). Material and methods. Seventy women who received adjuvant loco-regional RT for breast cancer during November 1994-May 1998 accepted to participate in this follow-up study. Pulmonary function tests (PFTs) (n = 56) were compared to pre-RT examinations and diagnostic computer tomography (CT) of the lungs (n = 70) were performed and compared to four months post-RT examinations. Result. The median-matched vital capacity (VC), forced expiratory volume in one second (FEV1), and total lung capacity (TLC) were reduced 15%, 9%, and 7%, respectively, at the long-term follow-up (p < 0.001). We could not, however, detect a correlation between ipsilateral V-20 and VC-changes. Diffusion capacity (DLCO) appeared to improve compared with the pre-RT baseline level probably due to transient chemotherapy-induced toxicity. The median-matched percentage of the predicted DLCO 11 years after RT was, however, only 86%, indicating a chronic therapy-induced reduction also of this metric. According to the Arriagada classification, ipsilateral V-20 and long-term CT-changes showed a significant correlation (r(s) : 0. 57; p<0.001) in a small subset of the women. Conclusion. A chronic clinically significant reduction of PFTs compared to pre-RT values and CT-changes four months after RT were still detectable after a median follow-up of 11 years. There was a statistical correlation between V-20 and abnormalities on CT but no statistical correlation between V-20 and VC-changes.
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| 5. |
- Wennberg, Ann-Marie, 1956, et al.
(författare)
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Photodynamic therapy with methyl aminolevulinate for prevention of new skin lesions in transplant recipients: a randomized study
- 2008
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 86:3, s. 423-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Organ transplant recipients on long-term immunosuppressive therapy are at increased risk of non-melanoma skin lesions. Repeated field photodynamic therapy using topical methyl aminolevulinate (MAL) may have potential as a preventive treatment. METHODS: This open randomized, intrapatient, comparative, multicenter study included 81 transplant recipients with 889 lesions (90% actinic keratoses (AK)]. In each patient, the study treatment was initially administered to one 50 cm area on the face, scalp, neck, trunk, or extremities (n=476 lesions) twice (1 week apart), with additional single treatments at 3, 9, and 15 months. On each occasion, the area was debrided gently and MAL cream (160 mg/g) applied for 3 hr, before illumination with noncoherent red light (630 nm, 37 J/cm2). The control, 50 cm2 area (n=413 lesions) received lesion-specific treatment (83% cryotherapy) at baseline and 3, 9, and 15 months. Additionally, all visible lesions were given lesion-specific treatment 21 and 27 months in both treatment and control areas. RESULTS: At 3 months, MAL photodynamic therapy significantly reduced the occurrence of new lesions (65 vs. 103 lesions in the control area; P=0.01), mainly AK (46% reduction; 43 vs. 80; P=0.006). This effect was not significant at 27 months (253 vs. 312; P=0.06). Hypopigmentation, as assessed by the investigator, was less evident in the treatment than control areas (16% vs. 51% of patients; P<0.001) at 27 months. CONCLUSION: Our results suggest that repeated field photodynamic therapy using topical MAL may prevent new AK in transplant recipients although further studies are needed.
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| 6. |
- Wennberg, Berit M., et al.
(författare)
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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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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 50:4, s. 518-527
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Wennberg, Berit
(författare)
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The effect of spatial and temporal dose distributions on radiation-induced side effects in the lung
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In radiotherapy (RT), the aim is to kill all malignant cells in a tumor or to render them incapable of further division and multiplication without producing damage to the normal tissues surrounding the tumor. To achieve this, both the spatial and temporal distribution of dose delivery are important for optimizing the treatment. A sufficiently high dose must be delivered to the tumor cells and as low a dose as possible to normal tissues. The number of fractional doses delivered also impacts outcome due to the time-dependent repair of sublethal radiation damage, which differs in tumor and normal cells. In patients undergoing RT for tumors located in and near the thorax, irradiation of the healthy lung may induce radiation pneumonitis (RP), which can be a serious problem. Understanding the factors involved in the onset of RP is important for reducing its incidence. The overall aim of the thesis was to determine if radiation-induced side effects in lung can be modelled in terms of the spatial and temporal distributions of the doses delivered in conventional RT for breast cancer (BC) and hypofractionated stereotactic body radiotherapy (SBRT) for lung cancer. Radiological changes in the lung were quantified with Computer Tomography (CT) after RT in 121 patients with breast cancer (BC). Their association with the spatial dose distribution as well as incidence of RP where studied. It was found that RP and radiological findings were associated with the spatial dose distribution. In a subgroup of 87 patients, data of the spatial dose distribution and incidence of RP were modelled using four different normal tissue complication probability (NTCP) models. The studied models fit quite accurately to data for the considered endpoints. Mean lung dose was shown to be a robust and simple parameter that correlated with the risk of RP. The calculated spatial dose distribution in SBRT of tumors in the lungs, including breathing motions, were assessed for accuracy. The analysis showed that the dose in the central part of the gross tumor volume (GTV) was accurate to within 2–3% for commonly used algorithms; however in the lung tissue close to the GTV the different algorithms both over- and underestimates it, depending on type. When clinically relevant breathing motions were considered, the dose calculated for a static situation remained a relatively accurate estimate of the dose in the GTV. Data of dose distributions and incidence of RP after SBRT for lung cancer were fitted to a NTCP model in a cohort of 57 patients. Correction for fractionation was done in two ways: with the Linear-Quadratic (LQ) model and the Universal Survival Curve (USC). The modelling showed that low dose volumes contributes less to NTCP and high dose volumes comparatively more with the USC model, than the LQ model. The impact of fractionation in SBRT was analyzed using the LQ- and USC models for fractionation correction. The therapeutic window was shown to increase with number of fractions for a range of regimes (2 to 20 fractions) at target doses common in SBRT. Generally, a larger gain was predicted with the USC correction. At high doses per fraction, typical in SBRT, the USC model predicted a lower sensitivity for fractionation as compared to the LQ model. In conclusion, the incidence of RP can be modelled, accounting for spatial and temporal dose distributions, especially in conventional RT of BC. In SBRT, with a more focused irradiation to very high doses, some uncertainties remain, both regarding the dependence of the spatial dose distribution and particularly of fractionation. The modelling shows that a less extreme hypo fractionation in SBRT may be a way to increase indications for SBRT. Generally, more data is needed for improved modelling.
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