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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) (α/β = 3 Gy) was EQD(2,LQ) = 147 Gy3 (range, 20-293 Gy3). For patients who developed atelectasis the median value was EQD(2,LQ) = 210 Gy3, and for patients who did not develop atelectasis, EQD(2,LQ) = 105 Gy3. 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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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.

Background and Purpose: The aim of this study is to analyse the dose-response and the volume-response of radiation-induced rib fractures after hypofractionated stereotactic body radiation therapy (SBRT)., Materials and Methods: During the period 1998-2005, 68 patients with medically inoperable stage I non-small cell lung cancer (NSCLC) were treated with hypofractionated SBRT to 45 Gy in 3 fractions. Among the 33 patients with complete treatment records and radiographic follow-up exceeding 15 months (median: 29 months), 13 fractures were found in seven patients. Identifying all ribs receiving at least 21 Gy, 81 ribs (13 with and 68 without fracture) in 26 patients were separately contoured and their dose-volume histograms (DVHs) were obtained. The DVHs were assessed with the mean dose and cut-off models. Maximum likelihood estimation was used to fit dose-response and volume-response curves to each model., Results: It was possible to quantify the risk of radiation-induced rib fracture using response curves and information contained in the DVHs. Absolute volumes provided better fits than relative volumes and dose-response curves were more suitable than volume-response curves. For the dose given by the 2 cm(3) cut-off volume, D(2 cm(3)), the logistic dose-response curve for three fractions was parameterised by D(50)=49.8 Gy and gamma(50)=2.05. Consequently, for a median follow-up of 29 months, if D(2 cm(3))<3 x 7.0 Gy the risk is close to 0, and the 5% and 50% risks are given by D(2 cm(3))=3 x 9.1 Gy and 3 x 16.6 Gy, respectively., Conclusions: In this group of patients, the risk for radiation-induced rib fracture following hypofractionated SBRT was related to the dose to 2 cm(3) of the rib.

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.

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.

Unlabelled: Medically inoperable patients with stage I NSCLC are mainly offered conventionally fractionated radiotherapy with a limited chance of local control and some toxicity. A technique for stereotactic precision therapy for extracranial tumors using a linear accelerator and a body frame for patient immobilization was applied in an attempt to improve the local control and decrease toxicity for consecutive patients with inoperable stage I NSCLC at Sahlgrenska University hospital since 1998. A hypofractionated schedule with three fractions of 15Gy to a total of 45 Gy during 1 week was used which represents a biological equivalent dose (BED) of 112.5 Gy. Planning target volume (PTV) was a 5mm margin around the tumor in the transversal plane and 10mm in the cranial-caudal direction and the dose was prescribed in the periphery of the PTV. Forty-five patients were treated between September 98 and March 03, 25 men and 20 women, median age 74 years (58-84) and median Karnofsky 80 (100-60). TNM: 18 T1N0, 27 T2N0., Histology: 18 squamous cell carcinoma, 15 adenocarcinoma, 3 NSCLC and histology was missing in nine patients. The majority, 51%, did not experience any toxicity at all, four had esophagitis grade I, nine had skin reactions, four had transient chest pain and four had infections. Late toxicity was two rib fractures and three patients with atelectasias. After a median follow-up of 43 months had nine patients developed local recurrence or never achieved local control, two had regional recurrence and nine distant metastases. The 1-, 2-, 3- and 5-year overall survival was 80, 71, 55 and 30%, respectively, with a median survival of 39 months. No prognostic factor for survival could be identified among histology, tumor stage and size, gender and age. We think this hypofractionated stereotactic radiotherapy shows encouraging survival and a relatively low toxicity in this elderly population with substantial comorbidity. A multicenter randomized trial comparing this treatment with conventional fractionated radiotherapy is under way.

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.