Biomedical subjects

Karl-Axel Johansson

Publications and source records attributed to Karl-Axel Johansson.

12 recordsLinked to original sources

PubMed2006

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.

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.

Aged↗

PubMed2006

Dummy run for a phase II study of stereotactic body radiotherapy of T1-T2 N0M0 medical inoperable non-small cell lung cancer.

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.

Carcinoma, Non-Small-Cell Lung↗

PubMed2005

Stereotactic hypofractionated radiotherapy for stage I non-small cell lung cancer--mature results for medically inoperable patients.

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.

Aged↗

PubMed2005

Does electron and proton therapy reduce the risk of radiation induced cancer after spinal irradiation for childhood medulloblastoma? A comparative treatment planning study.

The aim of this treatment planning comparison study was to explore different spinal irradiation techniques with respect to the risk of late side-effects, particularly radiation-induced cancer. The radiotherapy techniques compared were conventional photon therapy, intensity modulated x-ray therapy (IMXT), conventional electron therapy, intensity/energy modulated electron therapy (IMET) and proton therapy (IMPT).CT images for radiotherapy use from five children, median age 8 and diagnosed with medulloblastoma, were selected for this study. Target volumes and organs at risk were defined in 3-D. Treatment plans using conventional photon therapy, IMXT, conventional electron therapy, IMET and IMPT were set up. The probability of normal tissue complication (NTCP) and the risk of cancer induction were calculated using models with parameters-sets taken from published data for the general population; dose data were taken from dose volume histograms (DVH). Similar dose distributions in the targets were achieved with all techniques but the absorbed doses in the organs-at-risk varied significantly between the different techniques. The NTCP models based on available data predicted very low probabilities for side-effects in all cases. However, the effective mean doses outside the target volumes, and thus the predicted risk of cancer induction, varied significantly between the techniques. The highest lifetime risk of secondary cancers was estimated for IMXT (30%). The lowest risk was found with IMPT (4%). The risks associated with conventional photon therapy, electron therapy and IMET were 20%, 21% and 15%, respectively. This model study shows that spinal irradiation of young children with photon and electron techniques results in a substantial risk of radiation-induced secondary cancers. Multiple beam IMXT seems to be associated with a particularly high risk of secondary cancer induction. To minimise this risk, IMPT should be the treatment of choice. If proton therapy is not available, advanced electron therapy may provide a better alternative.

Child↗

PubMed2005

Accelerated radiotherapy for advanced laryngeal cancer.

The purpose of this study was to evaluate a single institution's outcome for patients with advanced laryngeal cancer treated with accelerated radiotherapy (RT). Fifty-eight patients with advanced laryngeal cancer (T3/T4N0/N + M0) were treated with curative intent with accelerated RT during the period 1990-1998. Patients received radiotherapy alone or with induction chemotherapy. The 5-year local control (LC) and loco-regional control (LRC) probabilities were both 49% for T3 and 75% for T4 tumors. The 5-year disease-free survival probability was 46% and 68% and overall survival probability was 30% and 39% for T3 and T4 tumors respectively. No significant statistical difference in outcome was found, either between T3 and T4 tumors, or between patients who received induction chemotherapy and those who did not. The treatment results for advanced laryngeal cancer at this institution were comparable to those reported in the literature. The results for T3 and T4 were similar. T4 classification alone should not be an exclusion criterion for larynx preservation. Overall survival was poor, partly because of a high incidence of deaths from intercurrent diseases.

Adult↗

PubMed2004

DNA double strand break quantification in skin biopsies.

BACKGROUND AND PURPOSE: Following induction of double strand breaks the histone H2AX is rapidly phosphorylated at regions flanking the breaks resulting in nuclear gamma H2AX foci. The purpose of this study was to use this endogenous signalling system to quantify the in vivo response to radiation in normal tissue. PATIENTS AND METHODS: Skin biopsies were taken from prostate cancer patients undergoing radiotherapy with a curative intent. Biopsies were taken at locations corresponding to 5 different doses in the range below 1.1 Gy per fraction. Biopsies were taken from patients 30 min following the first fraction and then once again following the fraction given after the first weekend break in the treatment course. The DNA double strand breaks were visualised as gamma H2AX foci using immunohistochemistry. Images were acquired using a CCD-camera and a fluorescence microscope and the gamma H2AX foci were quantified using digital image analysis including the basic procedures of top-hat transformation, threshold setting and labelling. RESULTS: Repeated assessments of the biopsies showed a high reproducibility in quantifying the number of foci per DNA area of the nucleated cells in epidermis. The reproducibility was equally good for the two biopsy occasions. A linear dose response was observed for the epidermis in the dose region 0-1 Gy. CONCLUSIONS: We have established a method to measure the relative amount of DNA double strand breaks by detecting gamma H2AX foci in patients exposed to radiotherapy. The method provides a tool to study induction and repair of DNA double strand breaks and has the potential to predict individual radiosensitivity.

Biopsy↗

PubMed2003

Intensity modulated radiotherapy treatment planning for dynamic multileaf collimator delivery: influence of different parameters on dose distributions.

BACKGROUND AND PURPOSE: This is an investigation of a dose-based conjugated gradient optimization method (implemented in the CadPlan/Helios system) applied for head and neck tumours. Optimized field fluence distributions are created and transformed into dynamic multileaf collimator (MLC) movements. The aim was to gain knowledge about the influence of different parameters on the dose distribution and how to use the optimization algorithm in an optimum way. MATERIAL AND METHODS: Parameters such as the number of beams, collimator angle and constraints and weight factors have been investigated. Dose escalation to the target volume, the target volume in the build-up region and the way of prescribing the target dose were also investigated. The dose distributions were mainly analysed with physical parameters. RESULTS AND CONCLUSIONS: The optimization algorithm is well suited to create clinical Intensity modulated radiation therapy (IMRT) treatment plans for head and neck tumours even when the target volume is situated in the build-up region. The number of beams is a critical parameter and has a great influence on the dose distribution. The choice of collimator angles is not a critical parameter. The constraints and weight factors have a great influence on the dose distribution and varying these could easily control priorities regarding dose to the target volume or to the surrounding critical organs. Because of dose variations inside the target volume, prescribing to, normalizing to and reporting the mean dose in the target volume for IMRT treatment plans is preferable to the absorbed dose at a point, for example the isocentre point.

Algorithms↗

PubMed2003

Systematic set-up errors for IMRT in the head and neck region: effect on dose distribution.

BACKGROUND AND PURPOSE: There is a general concern about intensity modulated radiation therapy (IMRT) treatments being more sensitive to patient positioning than conventional treatments. The aim of this study was to evaluate the International Commission on radiation units and measurements (ICRU) method for taking systematic set-up errors into account for IMRT treatments and to compare the effects on the dose distribution with the effects of conventional treatments. MATERIAL AND METHODS: A planning margin to account for set-up errors was added to the clinical target volumes and to the spinal cords, for three head and neck patients, according to the ICRU. No margin was added to organs at risk with mainly parallel structure if they were situated adjacent to the target volume, for example, the parotid glands. The effects of set-up errors in six IMRT plans and three conventional plans were simulated in the planning system and analysed with physical dose parameters. RESULTS AND CONCLUSIONS: In general, the ICRU method of taking set-up errors into account works satisfactorily for IMRT treatments as well as for conventional treatments with no difference between the treatment techniques. The sensitivity to set-up errors regarding the target volume is dependent on the quality of the treatment plan, i.e. the part of the target covered with a dose >95 and <105% and the effect in the critical organs is dependent on the sharpness of the dose gradients outside the critical organ. However, the method makes it difficult to include organs at risk with mainly parallel structure if they are situated adjacent to the target volume.

Head and Neck Neoplasms↗

PubMed2003

Radiation therapy dose delivery.

In an investigation by the Swedish Cancer Society, the present status critical issues and future aspects and potentials in each of nine major areas of radiation therapy research were described by an expert group. The report presented here deals with radiation therapy dose delivery. dose distributions, beam shaping and intensity modulation.

Humans↗

PubMed2003

The potential of proton and light ion beams in radiotherapy.

In an investigation by the Swedish Cancer Society, the present status, critical issues and future aspects and potentials were described by an expert group for each of nine major areas of radiation therapy research. The present report deals with the potential of proton and light ion beams in radiotherapy.

Humans↗

PubMed2002

Hyperfractionated-accelerated or conventionally fractionated radiotherapy for early glottic cancer.

PURPOSE: To evaluate the effect of shortening overall treatment time by hyperfractionated-accelerated radiotherapy for T2N(0)M(0) glottic carcinomas. Results for local control and survival were calculated and compared to those for T1N(0)M(0) tumors treated with a once-a-day fractionated schedule. METHODS AND MATERIALS: Between 1990 and 1998, 92 patients with T1N(0)M(0) and 45 patients with T2N(0)M(0) glottic cancers were treated with radical radiotherapy. The T1N(0)M(0) tumors were treated with a once-a-day fractionated schedule lasting 6.5 weeks to a total dose of 62.4 Gy. The T2N(0)M(0) tumors received a split-course hyperfractionated-accelerated treatment over a total of 4.5 weeks to a total dose of 64.6 Gy. RESULTS: The 5-year local control was 85% for T1N(0)M(0) and 88% for T2N(0)M(0), whereas the 5-year locoregional control was 85% for both groups. The 5-year overall survival was 70% and 53% for T1N(0)M(0) and T2N(0)M(0), respectively. No significant statistical difference was found between the two groups for the parameters analyzed. The number of serious late complications was few and comparable for the two groups. CONCLUSIONS: Hyperfractionated-accelerated radiotherapy proved beneficial for T2N(0)M(0) glottic cancer, giving local control rates comparable to those for T1N(0)M(0) tumors.

Adult↗

PubMed2002

Swedish Cancer Society radiation therapy research investigation.

In an investigation by the Swedish Cancer Society, the present status, critical issues and future aspects and prospects were described by an expert group for each of nine major areas of radiation research. A summary of the investigation is presented in this report. A more extensive summary (in Swedish) can be found at www.Cancerfonden.se. It is concluded that radiation therapy plays an increasingly important role in curative and palliative tumour treatment and presents a considerable challenge to research. Several suggestions are made that could improve the possibilities for high-quality radiation therapy research in Sweden.

Humans↗