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Mikko Tenhunen

Publications and source records attributed to Mikko Tenhunen.

18 recordsLinked to original sources
PubMed2006

The influence of output measurement time interval and tolerance on treatment dose deviation in photon external beam radiotherapy.

A method was developed to estimate the spread of treatment doses due to a given output measurement, time interval and action level in external photon beam radiotherapy. The method exploits empirical or simulated data of both output stability and the reproducibility of the absolute output measurements and relative constancy checks. The spread of an output and the probability that an output is outside the predefined tolerance limits were estimated for different quality control procedures of the output. The use of internationally recommended output measurement intervals of 3, 1 and 0.25 months together with an action level of +/-2% results in the out-of-tolerance probability up to 49%, 26% and 3%, respectively, while the output is kept within up to +/-5.5%, +/-4.0% and +/-2.0%, respectively. It was also found that the action level has more prominent relative influence than the measurement interval. The results suggest that similar treatment quality can be achieved by doubling the output measurement time interval and lowering the action level from +/-2% to +/-1.5% and the constancy check action level from +/-3% to +/-2%.

Algorithms↗
PubMed2006

Analysis of quality control data of eight modern radiotherapy linear accelerators: the short- and long-term behaviours of the outputs and the reproducibility of quality control measurements.

Quality control (QC) data of radiotherapy linear accelerators, collected by Helsinki University Central Hospital between the years 2000 and 2004, were analysed. The goal was to provide information for the evaluation and elaboration of QC of accelerator outputs and to propose a method for QC data analysis. Short- and long-term drifts in outputs were quantified by fitting empirical mathematical models to the QC measurements. Normally, long-term drifts were well (< or =1%) modelled by either a straight line or a single-exponential function. A drift of 2% occurred in 18 +/- 12 months. The shortest drift times of only 2-3 months were observed for some new accelerators just after the commissioning but they stabilized during the first 2-3 years. The short-term reproducibility and the long-term stability of local constancy checks, carried out with a sealed plane parallel ion chamber, were also estimated by fitting empirical models to the QC measurements. The reproducibility was 0.2-0.5% depending on the positioning practice of a device. Long-term instabilities of about 0.3%/month were observed for some checking devices. The reproducibility of local absorbed dose measurements was estimated to be about 0.5%. The proposed empirical model fitting of QC data facilitates the recognition of erroneous QC measurements and abnormal output behaviour, caused by malfunctions, offering a tool to improve dose control.

Calibration↗
PubMed2006

Sparing of the submandibular glands by intensity modulated radiotherapy in the treatment of head and neck cancer.

BACKGROUND AND PURPOSE: The submandibular glands produce most of the unstimulated saliva output and are the key in prevention of radiation-related xerostomia. We investigated whether sparing of the submandibular function is feasible with intensity modulated radiotherapy (IMRT). PATIENTS AND METHODS: Thirty-six patients diagnosed with head and neck cancer were treated with IMRT and had at least one parotid gland excluded from the planning target volume. In a subset, of these patients (n=18) where the risk of cancer recurrence in the contralateral submandibular region was judged low, the contralateral submandibular gland was spared from full-dose irradiation. The total unstimulated and stimulated salivary flow rates and adverse effects were monitored. RESULTS: Twelve months following IMRT mean unstimulated saliva flow was 60% of the baseline value among patients who had one submandibular gland spared and 25% among those who did not (P=0.006). Patients whose contralateral submandibular was spared reported less grade two or three xerostomia (4 vs. 11; P=0.018), and used less saliva substitutes. No cancer recurrences were detected at the vicinity of the spared glands during a median follow-up time of 31 months. CONCLUSIONS: Submandibular gland sparing with IMRT is safe in selected patients treated for head and neck cancer. It is effective in prevention of radiation-associated xerostomia.

Adult↗
PubMed2006

Chemoradiotherapy of anal cancer is feasible in elderly patients: treatment results of mitomycin-5-FU combined with radiotherapy at Helsinki University Central Hospital 1992-2003.

The number of elderly patients with cancer is steadily increasing in developed countries and their treatment is a growing challenge for oncological departments. Anal cancer is the first tumour in which chemoradiotherapy with the intent of organ preservation has largely replaced surgery and is an interesting model of modern multimodal oncological treatment. At the Department of Oncology of the Helsinki University Central Hospital we have treated all patients irrespective of age following the same guidelines if there have been no specific contraindications on the basis of intercurrent diseases. The results suggest that the chemoradiotherapy protocol used in the treatment of anal cancer is reasonably well tolerated in elderly patients and the tumour control is comparable to those achieved in younger patients. After successful cancer therapy the life expectancy in these patients can be very long.

Adult↗
PubMed2006

Testing of the analytical anisotropic algorithm for photon dose calculation.

The analytical anisotropic algorithm (AAA) was implemented in the Eclipse (Varian Medical Systems) treatment planning system to replace the single pencil beam (SPB) algorithm for the calculation of dose distributions for photon beams. AAA was developed to improve the dose calculation accuracy, especially in heterogeneous media. The total dose deposition is calculated as the superposition of the dose deposited by two photon sources (primary and secondary) and by an electron contamination source. The photon dose is calculated as a three-dimensional convolution of Monte-Carlo precalculated scatter kernels, scaled according to the electron density matrix. For the configuration of AAA, an optimization algorithm determines the parameters characterizing the multiple source model by optimizing the agreement between the calculated and measured depth dose curves and profiles for the basic beam data. We have combined the acceptance tests obtained in three different departments for 6, 15, and 18 MV photon beams. The accuracy of AAA was tested for different field sizes (symmetric and asymmetric) for open fields, wedged fields, and static and dynamic multileaf collimation fields. Depth dose behavior at different source-to-phantom distances was investigated. Measurements were performed on homogeneous, water equivalent phantoms, on simple phantoms containing cork inhomogeneities, and on the thorax of an anthropomorphic phantom. Comparisons were made among measurements, AAA, and SPB calculations. The optimization procedure for the configuration of the algorithm was successful in reproducing the basic beam data with an overall accuracy of 3%, 1 mm in the build-up region, and 1%, 1 mm elsewhere. Testing of the algorithm in more clinical setups showed comparable results for depth dose curves, profiles, and monitor units of symmetric open and wedged beams below dmax. The electron contamination model was found to be suboptimal to model the dose around dmax, especially for physical wedges at smaller source to phantom distances. For the asymmetric field verification, absolute dose difference of up to 4% were observed for the most extreme asymmetries. Compared to the SPB, the penumbra modeling is considerably improved (1%, 1 mm). At the interface between solid water and cork, profiles show a better agreement with AAA. Depth dose curves in the cork are substantially better with AAA than with SPB. Improvements are more pronounced for 18 MV than for 6 MV. Point dose measurements in the thoracic phantom are mostly within 5%. In general, we can conclude that, compared to SPB, AAA improves the accuracy of dose calculations. Particular progress was made with respect to the penumbra and low dose regions. In heterogeneous materials, improvements are substantial and more pronounced for high (18 MV) than for low (6 MV) energies.

Algorithms↗
PubMed2005

Human breast cancer in vitro: matching histo-pathology with small-angle x-ray scattering and diffraction enhanced x-ray imaging.

Twenty-eight human breast tumour specimens were studied with small-angle x-ray scattering (SAXS), and 10 of those were imaged by the diffraction enhanced x-ray imaging (DEI) technique. The sample diameter was 20 mm and the thickness 1 mm. Two examples of ductal carcinoma are illustrated by histology images, DEI, and maps of the collagen d-spacing and scattered intensity in the Porod regime, which characterize the SAXS patterns from collagen-rich regions of the samples. Histo-pathology reveals the cancer-invaded regions, and the maps of the SAXS parameters show that in these regions the scattering signal differs significantly from scattering by the surrounding tissue, indicating a degradation of the collagen structure in the invaded regions. The DEI images show the borders between collagen and adipose tissue and provide a co-ordinate system for tissue mapping by SAXS. In addition, degradation of the collagen structure in an invaded region is revealed by fading contrast of the DEI refraction image. The 28 samples include fresh, defrosted tissue and formalin-fixed tissue. The d-values with their standard deviations are given. In the fresh samples there is a systematic 0.76% increase of the d-value in the invaded regions, averaged over 11 samples. Only intra-sample comparisons are made for the formalin-fixed samples, and with a long fixation time, the difference in the d-value stabilizes at about 0.7%. The correspondence between the DEI images, the SAXS maps and the histo-pathology suggests that definitive information on tumour growth and malignancy is obtained by combining these x-ray methods.

Breast Neoplasms↗
PubMed2005

Visualisation of calcifications and thin collagen strands in human breast tumour specimens by the diffraction-enhanced imaging technique: a comparison with conventional mammography and histology.

Six excised human breast tissue specimens carrying benign and malignant tumours were examined with the diffraction-enhanced imaging technique. Diffraction-enhanced images were compared with diagnostic screen-film mammograms and the correlation with histological information of the specimens was established. The enhanced visibility of calcifications, some of which were smaller than 0.15 mm in diameter, is reported in detail. Fine details of the structures such as strands of collagen and contours between glandular and adipose tissue, which are barely visible at the contrast detection limit in the conventional absorption-based mammograms, are clearly visible in the diffraction-enhanced images. Microscopic study of the stained histopathological sections unequivocally confirms the correlation of the radiographic findings with the morphologic changes in specimens. An increased soft tissue contrast and a combination of information obtained with disparate diffraction-enhanced images provide better visibility of mammographically indistinguishable features. This kind of additional structural information of the breast tissue is required to improve assessment accuracy and earlier detection of the breast lesions. These advances in image quality make the method a very promising candidate for mammography.

Breast Neoplasms↗
PubMed2004

Intensity modulated radiotherapy for head and neck cancer: evidence for preserved salivary gland function.

BACKGROUND AND PURPOSE: To investigate the salivary gland function following intensity modulated radiotherapy (IMRT) for head and neck cancer. PATIENTS AND METHODS: Seventeen patients with oropharyngeal (n=11) or nasopharyngeal (n=6) carcinoma located adjacent to the major salivary glands were treated with IMRT with an emphasis to spare the salivary glands from high-dose irradiation and to reduce the risk of postirradiation xerostomy. Three patients had stage 2, 4 stage III, and 10 stage IVA cancer. The total basal and stimulated saliva flow rates were measured before the treatment, and 6 and 12 months after radiotherapy. RESULTS: The median basal saliva flow rate measured before radiation treatment was 0.13 mL/min, and at 6 and 12 months after the completion of IMRT 0.04 mL/min and 0.07 mL/min, respectively. The corresponding median stimulated saliva flow rates were 0.49 mL/min, 0.33 mL/min, and 0.45 mL, respectively. The D50 for an impaired stimulated parotid gland saliva flow rate was 25.5 Gy. Only two (12%) patients developed grade 3 and none grade 4 xerostomia during a median follow-up of 24 months (range, 12-40 months). No patients had locoregional cancer recurrence following IMRT. CONCLUSIONS: The results suggest that much of the salivary gland function can be maintained with IMRT without jeopardizing the local control rate in the treatment of locally advanced oropharynx or nasopharynx carcinoma.

Adult↗
PubMed2004

Phase I-II trial of twice-weekly gemcitabine and concomitant irradiation in patients undergoing pancreaticoduodenectomy with extended lymphadenectomy for locally advanced pancreatic cancer.

PURPOSE: Define the maximum tolerated dose (MTD), tolerability, and efficacy of gemcitabine given concomitantly with radiotherapy in patients with locally advanced pancreatic cancer. METHODS AND MATERIALS: Patients were required to have locally advanced T1-T3 resectable pancreatic cancer. Gemcitabine, given twice weekly before irradiation as a 30-min infusion, was tested at 3 dose levels: 20, 50, and 100 mg/m(2). The radiation dose was 50.4 Gy (ICRU) in 28 fractions. The targeted irradiation volume included the tumor, edema, and a 1-cm margin. RESULTS: Twenty-eight of 34 patients was eligible for analysis of the treatment. The median age was 67 years (range 38-82). Six patients had T1, 9 had T2, and 19 had T3 diseases (AJCC). Dose-limiting toxicities were Grade 4, fatigue and nausea; Grade 3, thrombocytopenia, diarrhea, and infection. The MTD established was at the 50-mg/m(2) gemcitabine dose. A total of 21 of 28 patients underwent surgery: 18 had pancreaticoduodenectomy, 2 had total pancreatectomy, and 1 for palliative surgery. At the time of analysis, 13 of 28 (46%) were disease-free. The estimated median survival was 25 months and overall survival rate at 2 years (Kaplan-Meier) was 55%. CONCLUSION: Gemcitabine 50 mg/m(2) given twice weekly with concomitant irradiation induces acceptable and manageable toxicity and might prolong survival.

Adult↗
PubMed2004

Effects of acid sphingomyelinase deficiency on male germ cell development and programmed cell death.

Deficiency of acid sphingomyelinase (ASM), an enzyme responsible for producing a pro-apoptotic second messenger ceramide, has previously been shown to promote the survival of fetal mouse oocytes in vivo and to protect oocytes from chemotherapy-induced apoptosis in vitro. Here we investigated the effects of ASM deficiency on testicular germ cell development and on the ability of germ cells to undergo apoptosis. At the age of 20 weeks, ASM knock-out (ASMKO) sperm concentrations were comparable with wild-type (WT) sperm concentrations, whereas sperm motility was seriously affected. ASMKO testes contained significantly elevated levels of sphingomyelin at the age of 8 weeks as detected by high-performance, thin-layer chromatography. Electron microscopy revealed that the testes started to accumulate pathological vesicles in Sertoli cells and in the interstitium at the age of 21 days. Irradiation of WT and ASMKO mice did not elevate intratesticular ceramide levels at 16 h after irradiation. In situ end labeling of apoptotic cells also showed a similar degree of cell death in both groups. After a 21-day recovery period, the numbers of primary spermatocytes and spermatogonia at G2 as well as spermatids were essentially the same in the WT and ASMKO testes, as detected by flow cytometry. In serum-free cultures both ASMKO and WT germ cells showed a significant increase in the level of ceramide, as well as massive apoptosis. In conclusion, ASM is required for maintenance of normal sphingomyelin levels in the testis and for normal sperm motility, but not for testicular ceramide production or for the ability of the germ cells to undergo apoptosis.

Animals↗
PubMed2003

Protection from radiation-induced male germ cell loss by sphingosine-1-phosphate.

Male germ cells are susceptible to radiation-induced injury, and infertility is a common problem after total-body irradiation. Here we investigated, first, the effects of irradiation on germ cells in mouse testis and, second, the role of sphingosine-1-phosphate (S1P) treatment in radiation-induced male germ cell loss. Irradiation of mouse testes mainly damaged the early developmental stages of spermatogonia. The damage was seen by means of DNA flow cytometry 21 days after irradiation as decreasing numbers of spermatocytes and spermatids with increasing amounts of ionizing radiation (0.1-2.0 Gy). Intratesticular injections of S1P given 1-2 h before irradiation (0.5 Gy) did not protect against short-term germ cell loss as measured by in situ end labeling of DNA fragmentation 16 h after irradiation. However, after 21 days, in the S1P-treated testes, the numbers of primary spermatocytes and spermatogonia at G2 (4C peak as measured by flow cytometry) were higher at all stages of spermatogenesis compared with vehicle-treated testes, indicating protection of early spermatogonia by S1P, whereas the spermatid (1C) populations were similar. In conclusion, S1P appears to protect partially (16%-47%) testicular germ cells against radiation-induced cell death. This warrants further studies aimed at development of therapeutic agents capable of blocking sphingomyelin-induced pathways of germ cell loss.

Animals↗
PubMed2003

Stereotactic radiotherapy of symptomatic circumscribed choroidal hemangiomas.

PURPOSE: To determine feasibility of low-dose stereotactic radiotherapy in the treatment of symptomatic circumscribed choroidal hemangioma. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: Five consecutive patients with perifoveolar and peripapillary circumscribed choroidal hemangioma and visual symptoms from exudative retinal detachment. METHODS: A dose of 20 Gy was delivered stereotactically with linear accelerator. Tumor dimensions were determined by B-scan ultrasonography. MAIN OUTCOME MEASURES: Resolution of subretinal fluid, best-corrected visual acuity, and reduction in tumor height. RESULTS: Median tumor height at baseline was 2.8 mm (range, 2.0-4.2 mm). Two tumors were subfoveolar, two were juxtafoveolar, and one was extrafoveolar. Cystic macular edema and subretinal fibrosis were present in both eyes with subfoveolar tumor. Exudative retinal detachment resolved within a median of 5 months (response rate, 100%; 95% CI, 48%-100%). Median best-corrected visual acuity was 20/50 (range, 20/22-20/100) at diagnosis and 20/25 (range, 20/20-20/60) 20 months after treatment. Tumor height had decreased a median of 24% (range, 0%-31%) by 6 months and 29% (range, 9%-59%) by 20 months. Secondary retinal pigment epithelial mottling associated with tumor regression occurred in two patients. One eye developed a paracentral scotoma. CONCLUSIONS: Stereotactic radiotherapy can be targeted precisely enough to induce regression of subretinal fluid from circumscribed choroidal hemangiomas.

Adult↗
PubMed2002

Late radiation effects in the dog brain: correlation of MRI and histological changes.

PURPOSE: To determine the correlation between sequential changes in the brain of dogs after irradiation, as detected by magnetic resonance imaging (MRI), with the eventual appearance of histological lesions. Histology was performed 77-115 weeks after irradiation. MATERIALS AND METHODS: Groups of five beagle dogs were irradiated to the brain with single doses of 10, 12, 14 or 16 Gy of 6 MV photons, at the 100% iso-dose. Sequential MRIs were taken to detect changes in the brain for 77-115 weeks after irradiation. Dose-effect relationships were established for changes in the brain as detected by MRI, computerized tomography (CT), gross morphology and histology. The doses that caused a specified response in 50% of the animals (ED(50)+/-SE) were calculated from these dose-effect relationships for each endpoint. RESULTS: The ED50 values (+/-SE) for focal and diffuse changes on T2-weighted MR images were 11.0+/-1.1 and 10.8+/-0.9 Gy, respectively. The ED50 values (+/-SE) for contrast enhancement on T1-weighted MR images and on CT were 13.4+/-0.6 and 13.0+/-0.6 Gy, respectively. It was 11.4+/-0.6 Gy for any type of histological lesion (haemorrhage, reactive change or glial scar) 77-115 weeks after irradiation. For a macroscopic lesion the ED50 (+/-SE) value was 13.0+/-1.1 Gy. CONCLUSIONS: The presence of focal or diffuse changes on T2-weighted MR images was the best indicator for the eventual appearance of any type of histological lesion in the dog brain after irradiation with single doses of photons. The ED50 for any histological lesion did not differ significantly from the ED50 for a focal (P>0.35) or diffuse (P=0.3) change on T2-weighted MR images.

Animals↗
PubMed2002

Acceptance tests and quality control (QC) procedures for the clinical implementation of intensity modulated radiotherapy (IMRT) using inverse planning and the sliding window technique: experience from five radiotherapy departments.

BACKGROUND AND PURPOSE: An increasing number of radiotherapy centres is now aiming for clinical implementation of intensity modulated radiotherapy (IMRT), but--in contrast to conventional treatment--no national or international guidelines for commissioning of the treatment planning system (TPS) and acceptance tests of treatment equipment have yet been developed. This paper bundles the experience of five radiotherapy departments that have introduced IMRT into their clinical routine. METHODS AND MATERIALS: The five radiotherapy departments are using similar configurations since they adopted the commercially available Varian solution for IMRT, regarding treatment planning as well as treatment delivery. All are using the sliding window technique. Different approaches towards the derivation of the multileaf collimator (MLC) parameters required for the configuration of the TPS are described. A description of the quality control procedures for the dynamic MLC, including their respective frequencies, is given. For the acceptance of the TPS for IMRT multiple quality control plans were developed on a variety of phantoms, testing the flexibility of the inverse planning modules to produce the desired dose pattern as well as assessing the accuracy of the dose calculation. Regarding patient treatment verification, all five centres perform dosimetric pre-treatment verification of the treatment fields, be it on a single field or on a total plan procedure. During the actual treatment, the primary focus is on patient positioning rather than dosimetry. Intracavitary in vivo measurements were performed in special cases. RESULT AND CONCLUSION: The configurational MLC parameters obtained through different methods are not identical for all centres, but the observed variations have shown to be of no significant clinical relevance. The quality control (QC) procedures for the dMLC have not detected any discrepancies since their initiation, demonstrating the reliability of the MLC controller. The development of geometrically simple QC plans to test the inverse planning, the dynamic MLC modules and the final dose calculation has proven to be useful in pointing out the need to remodel the single pencil beam scatter kernels in some centres. The final correspondence between calculated and measured dose was found to be satisfactory by all centres, for QC test plans as well as for pre-treatment verification of clinical IMRT fields. An intercomparison of the man hours needed per patient plan verification reveals a substantial variation depending on the type of measurements performed.

Humans↗
PubMed2002

Palliative radiotherapy in the treatment of skeletal metastases.

Two-third of patients with metastatic cancer suffer from pain. Pain originating from skeletal metastases is the most common form of cancer pain. Bone pain, often exacerbated by pressure or movement, limits the patient's autonomy and social life. Pathological fracture and spinal cord compression are additional complications caused by bone metastases. Radiotherapy is effective in treating bone pain not adequately controlled by analgesics. Seventy percent of patients benefit from radiotherapy. Single and multifraction regimens are equally effective in relieving pain. Retreatment is needed somewhat more often following single fraction therapy. Most patients benefit from retreatment irrespectively of previous fractionation schedule. Hemibody irradiation and radioisotopes, e.g., strontium-89 and samarium-153 are used in treating scattered painful bone metastases. Radiotherapy is used for preventing pathological fracture by treating osteolytic lesions especially in the weight-bearing bones such as the spinal column and long bones. Radiotherapy is the treatment of choice in spinal cord compression, which is the most serious complication caused by bone secondaries. Radiotherapy provides efficient, well-tolerated and cost-effective palliative care.

Bone Neoplasms↗
PubMedDate not supplied

Boron neutron capture therapy of brain tumors: clinical trials at the finnish facility using boronophenylalanine.

Two clinical trials are currently running at the Finnish dedicated boron neutron capture therapy (BNCT) facility. Between May 1999 and December 2001, 18 patients with supratentorial glioblastoma were treated with boronophenylalanine (BPA)-based BNCT within a context of a prospective clinical trial (protocol P-01). All patients underwent prior surgery, but none had received conventional radiotherapy or cancer chemotherapy before BNCT. BPA-fructose was given as 2-h infusion at BPA-dosages ranging from 290 to 400 mg/kg prior to neutron beam irradiation, which was given as a single fraction from two fields. The average planning target volume dose ranged from 30 to 61 Gy (W), and the average normal brain dose from 3 to 6 Gy (W). The treatment was generally well tolerated, and none of the patients have died during the first months following BNCT. The estimated 1-year overall survival is 61%. In another trial (protocol P-03), three patients with recurring or progressing glioblastoma following surgery and conventional cranial radiotherapy to 50-60 Gy, were treated with BPA-based BNCT using the BPA dosage of 290 mg/kg. The average planning target dose in these patients was 25-29 Gy (W), and the average whole brain dose 2-3 Gy (W). All three patients tolerated brain reirradiation with BNCT, and none died during the first three months following BNCT. We conclude that BPA-based BNCT has been relatively well tolerated both in previously irradiated and unirradiated glioblastoma patients. Efficacy comparisons with conventional photon radiation are difficult due to patient selection and confounding factors such as other treatments given, but the results support continuation of clinical research on BPA-based BNCT.

Adult↗