First patients treated with a 1.5 T MRI-Linac: clinical proof of concept of a high-precision, high-field MRI guided radiotherapy treatment.

The integration of 1.5 T MRI functionality with a radiotherapy linear accelerator (linac) has been pursued since 1999 by the UMC Utrecht in close collaboration with Elekta and Philips. The idea behind this integrated device is to offer unrivalled, online and real-time, soft-tissue visualization of the tumour and the surroundings for more precise radiation delivery. The proof of concept of this device was given in 2009 by demonstrating simultaneous irradiation and MR imaging on phantoms, since then the device has been further developed and commercialized by Elekta. The aim of this work is to demonstrate the clinical feasibility of online, high-precision, high-field MRI guidance of radiotherapy using the first clinical prototype MRI-Linac. Four patients with lumbar spine bone metastases were treated with a 3 or 5 beam step-and-shoot IMRT plan. The IMRT plan was created while the patient was on the treatment table and based on the online 1.5 T MR images; pre-treatment CT was deformably registered to the online MRI to obtain Hounsfield values. Bone metastases were chosen as the first site as these tumors can be clearly visualized on MRI and the surrounding spine bone can be detected on the integrated portal imager. This way the portal images served as an independent verification of the MRI based guidance to quantify the geometric precision of radiation delivery. Dosimetric accuracy was assessed post-treatment from phantom measurements with an ionization chamber and film. Absolute doses were found to be highly accurate, with deviations ranging from 0.0% to 1.7% in the isocenter. The geometrical, MRI based targeting as confirmed using portal images was better than 0.5 mm, ranging from 0.2 mm to 0.4 mm. In conclusion, high precision, high-field, 1.5 T MRI guided radiotherapy is clinically feasible.

Comparison of lumbosacral transforaminal epidural steroid injection techniques in terms of radiation safety.

AIM: To investigate the difference in radiation exposure to the patients between oblique and posteroanterior view, initial approach techniques in fluoroscopy-guided lumbosacral transforaminal epidural steroid injections. PATIENTS & METHODS: Total amount of Kerma area product, elapsed time of the procedure and fluoroscopy time were obtained from medical records retrospectively. RESULTS: 28 patients were included in each group. Fluoroscopy time was significantly lower in group 1, but there was no statistically significant difference in terms of procedure time and Kerma area product. CONCLUSION: Radiation risk does not change between these approaches.

Lumbar-sacral bone marrow dose modeling for acute hematological toxicity in anal cancer patients treated with concurrent chemo-radiation.

The aim of the study was to model acute hematologic toxicity (HT) and dose to pelvic osseous structures in anal cancer patients treated with definitive chemo-radiation (CT-RT). A total of 53 patients receiving CT-RT were analyzed. Pelvic bone marrow and corresponding subsites were contoured: ilium, lower pelvis and lumbosacral spine (LSBM). Dose-volume histograms points and mean doses were collected. Logistic regression was performed to correlate dosimetric parameters and ≥G3 HT as endpoint. Normal tissue complication probability (NTCP) was evaluated with the Lyman-Kutcher-Burman (LKB) model. Logistic regression showed a significant correlation between LSBM-mean dose and ≥G3 leukopenia (ß coefficient 0.122; p = 0.030; 95% CI 0.012-0.233). According to NTCP modeling, the predicted HT probability had the following parameters: TD50: 37.5 Gy, γ 50: 1.15, m: 0.347. For node positive patients, TD50: 35.2 Gy, γ 50: 2.27, m: 0.176 were found. Node positive patients had significantly higher PBM-V15 (Mean 81.1 vs. 86.7%; p = 0.04), -V20 (Mean 72.7 vs. 79.9%; p = 0.01) and V30 (Mean 50.2 vs. 57.3%; p = 0.03). Patients with a mean LSBM dose >32 Gy had a 1.81 (95% CI 0.81-4.0) relative risk to develop ≥G3 leukopenia. For node positive patients, those risks were 2.67 (95% CI 0.71-10). LKB modeling seems to suggest that LSBM-mean dose should be kept below 32 Gy to minimize ≥G3 HT in anal cancer patients treated with IMRT and concurrent chemotherapy. The contribution of LSBM dose in the development of HT above 25 Gy seems steeper in node positive patients.

Impact of chemotherapy on normal tissue complication probability models of acute hematologic toxicity in patients receiving pelvic intensity modulated radiation therapy.

PURPOSE: To determine how chemotherapy agents affect radiation dose parameters that correlate with acute hematologic toxicity (HT) in patients treated with pelvic intensity modulated radiation therapy (P-IMRT) and concurrent chemotherapy. METHODS AND MATERIALS: We assessed HT in 141 patients who received P-IMRT for anal, gynecologic, rectal, or prostate cancers, 95 of whom received concurrent chemotherapy. Patients were separated into 4 groups: mitomycin (MMC) + 5-fluorouracil (5FU, 37 of 141), platinum ± 5FU (Cis, 32 of 141), 5FU (26 of 141), and P-IMRT alone (46 of 141). The pelvic bone was contoured as a surrogate for pelvic bone marrow (PBM) and divided into subsites: ilium, lower pelvis, and lumbosacral spine (LSS). The volumes of each region receiving 5-40 Gy were calculated. The endpoint for HT was grade ≥3 (HT3+) leukopenia, neutropenia or thrombocytopenia. Normal tissue complication probability was calculated using the Lyman-Kutcher-Burman model. Logistic regression was used to analyze association between HT3+ and dosimetric parameters. RESULTS: Twenty-six patients experienced HT3+: 10 of 37 (27%) MMC, 14 of 32 (44%) Cis, 2 of 26 (8%) 5FU, and 0 of 46 P-IMRT. PBM dosimetric parameters were correlated with HT3+ in the MMC group but not in the Cis group. LSS dosimetric parameters were well correlated with HT3+ in both the MMC and Cis groups. Constrained optimization (0

[Structural changes in the sensory ganglia of the spinal nerves after repeated magnetic stimulation on the model of ischemic myelopathy].

The aim of this study was to examine the association of morphological changes in the-sensory ganglia of the spinal nerves (SGSN) with the cilinical symptomatology in rats with the experimentally induced ischemic myelopathy (IM), untreated or treated with repeated magnetic stimulation (RMS). The efficacy and mechanisms of RMS action on SGSN were studied by electron microscopy in 16 rats with IM. According to the results of treatment, in SGSN both at a distance from the damaged area (lumbar SGSN) and close to it (cervical SGSN) the morphological signs of regenerative-reparative processes were found in the cells and nerve fibers (restoration of the organelle structure in the cytoplasm o0f neurons and neurolemmocytes, the increase in the number of he latter and fiber remyelination). The expression of the structural changes correlated with the degree of functional recovery.

Gluteal artery perforator flap: a viable alternative for sacral radiation ulcer and osteoradionecrosis.

Radiotherapy is a crucial part in the treatment of cancer; however, it may cause adverse effects to normal tissue such as radiation-induced ulcer and osteoradionecrosis. The few cases of conservative management that were reported had a limited value and unsatisfactory results. The most reliable method to treat sacral radiation ulcer and osteoradionecrosis is a wide excision of the affected tissue, followed by coverage with well-vascularised tissue. Musculocutaneous free flaps and local gluteus maximus musculocutaneous flaps have been used; however, there were many drawbacks such as dissection of recipient vessel in the previously radiated area and donor-site morbidity. During a 4-year time period at our institute, we found favourable clinical results using gluteal artery perforator procedure for radiation-induced ulcers and osteoradionecrosis of the sacral area. The 10 patients, who were treated with gluteal artery perforator flaps, had chronic non-healing radiation ulcers or bone exposure of the sacrum. Intra-operatively, massive debridement of bone and soft tissue was performed, while the well-vascularised skin with only a colour change was preserved. The flap was designed to include two or more perforators using Doppler flowmetry and the perforators were preserved with surrounding subcutaneous tissue during the flap elevation. The mean post-operative follow-up period was 25.7 months. As regards the surgery, there was one major complication (of partial flap loss) and three minor complications (of wound dehiscence). In the patient with partial flap loss due to infection and a floating flap, the contralateral superior gluteal artery perforator flap was used to treat complications. Other complications were conservatively treated and well healed. Gluteal perforator flaps are a valuable alternative in treating sacral radiation ulcers and osteoradionecrosis. Sufficient excision of devitalised tissue is a crucial procedure to achieve optimal results.

Dosimetric predictors of acute hematologic toxicity in cervical cancer patients treated with concurrent cisplatin and intensity-modulated pelvic radiotherapy.

PURPOSE: To identify dosimetric parameters associated with acute hematologic toxicity (HT) and chemotherapy delivery in cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated pelvic radiotherapy. METHODS AND MATERIALS: We analyzed 37 cervical cancer patients receiving concurrent cisplatin (40 mg/m(2)/wk) and intensity-modulated pelvic radiotherapy. Pelvic bone marrow (BM) was contoured for each patient and divided into three subsites: lumbosacral spine, ilium, and lower pelvis. The volume of each region receiving 10, 20, 30, and > or =40 Gy (V(10), V(20), V(30), and V(40), respectively) was calculated. HT was graded according to the Radiation Therapy Oncology Group system. Multivariate regression models were used to test associations between dosimetric parameters and HT and chemotherapy delivery. RESULTS: Increased pelvic BM V(10) (BM-V(10)) was associated with an increased Grade 2 or worse leukopenia and neutropenia (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.24-3.53; p = 0.006; and OR, 1.41; 95% CI, 1.02-1.94; p = 0.037, respectively). Patients with BM-V(10) > or =90% had higher rates of Grade 2 or worse leukopenia and neutropenia than did patients with BM-V(10) <90% (11.1% vs. 73.7%, p < 0.01; and 5.6% vs. 31.6%, p = 0.09) and were more likely to have chemotherapy held on univariate (16.7% vs. 47.4%, p = 0.08) and multivariate (OR, 32.2; 95% CI, 1.67-622; p = 0.02) analysis. No associations between HT and V(30) and V(40) were observed. Dosimetric parameters involving the lumbosacral spine and lower pelvis had stronger associations with HT than did those involving the ilium. CONCLUSION: The volume of pelvic BM receiving low-dose radiation is associated with HT and chemotherapy delivery in cervical cancer patients undergoing concurrent chemoradiotherapy.

Application of heat- and steam-generating sheets to the lumbar or abdominal region affects autonomic nerve activity.

Effects of applying a heat- and steam-generating (HSG) sheet on peripheral hemodynamics and autonomic nerve activity were examined. An HSG sheet was applied to the lumbar or abdominal region. Measurements included skin temperature at the lumbar and abdominal regions and the fingertip, total hemoglobin, tissue oxygen saturation ratio (StO2), pupillary light reflex, changes in ECG R-R interval blood pressure and percutaneous electrogastrography (EGG). A heat-generating sheet without steam was used as the control. Based on the present findings, application of the HSG sheet to the lumbar or abdominal region may improve peripheral hemodynamics and inhibit sympathetic nerve activity, resulting in parasympathetic nerve activity dominance.

[Gadolinium enhancement of the anterior portion of the lumbosacral roots in a case of post-irradiation lumbosacral radiculopathy].

A 35-year-old woman, who underwent the removal of her uterus as a result of treatment for cancer of the cervix, developed weakness in the distal lower limbs after 8 months of subsequent radiation therapy. Although she could not walk because of distal dominant weakness and atrophy in the legs, no sensory disturbances were observed. An MRI scan showed gadolinium enhancement of the anterior portion of the lumbosacral roots in the cauda equina, which corresponded to her neurological symptoms. The administration of corticosteroid and warfarin dramatically alleviated her neurological symptoms, and a follow-up MRI scan one month later demonstrated a marked diminution of the gadolinium enhancement. There were only seven reports describing the abnormalities of the MRI findings, all of which noted the gadolinium enhancement of the anterior portion of the lumbosacral roots. Together with the findings in other reports, the enhancement abnormalities seem to be characteristic of post-irradiation lumbosacral radiculopathy.

X-irradiation of adult spinal cord increases its capacity to support neurite regeneration in vitro.

Previous in vitro studies have shown that X-irradiation during early postnatal life can change the environment of CNS tissue in later adult life such that it becomes more supportive of neurite regeneration from adult dorsal root ganglion (DRG) neurons than non-irradiated tissue. The question arises whether or not x-irradiation during adult life can alter the CNS environment such that it also becomes more supportive of neurite regeneration. This was investigated by exposing portions of the spinal cord of adult rats to 10, 20 or 40 Gray of X-irradiation and later using this tissue to prepare cryosections suitable for use as a substrate in a cryoculture assay. Fixed cryocultures were immunolabelled using anti-glial fibrillary acidic protein (GFAP) to visualise the tissue sections and anti-growth associated protein (GAP-43) to visualise the regenerating neurites. Tissue sections from sham-irradiated animals and from those irradiated with 10 Gray did not support the regeneration of neurites. However, sections of spinal cords from rats treated with either 20 or 40 Gray of X-irradiation 4 or 32 days prior to sampling were found to support a certain degree of neurite regeneration. It is concluded that X-irradiation of adult CNS tissue can alter its environment such that it becomes more supportive of neurite regeneration and it is speculated that this change may be the result of alterations in the glial cell populations in the post-irradiated tissues.

[Laser-evoked potentials: diagnostic approach to the dorsal root]. / Laserevozierte Potentiale: der diagnostische Zugang zur Hinterwurzel.

Functional diagnostics of the dorsal root are especially effective via nociceptive fibers on account of less intersegmental overlap compared to large-diameter fibers of the mechanoreceptive afferents. Laser-evoked potentials (LEP) are induced by short, painful heat stimuli. The aim of this work was to describe changes of the LEP in cases of dorsal root damage. The recorded LEP changes will be discussed with regard to their prognostic value as well as pathophysiologic aspects of dorsal root damage. Dorsal root function was tested in 21 patients suffering from clinically proven radiculopathy in one of the segments L4 to S1. Mechanosensibility and thermosensibility were clinically investigated. LEP were induced by slightly painful stimuli (80 on the affected and 80 on the contralateral unaffected dermatome). The LEP were evaluated by amplitude of the averaged electroencephalogram (EEG). In addition, a subjective pain rating was recorded after each stimulus. Investigation of dorsal root function by LEP in patients with radiculopathy yields two typical changes of the amplitude. On the one hand, there were significant reductions of amplitude, and on the other hand, a complete loss of LEP was found. LEP changes allow a graduation of patients who show no obvious differences in their clinical appearance. Which mechanisms are responsible as concerns deafferentiation and neuropathy of the dorsal root fibers are discussed. With regard to the LEP changes, a prognostic relevance in patients with dorsal root affections is likely. This question will be addressed in a prospective study soon.

[Metabolic reactions in sensory and motor neurons after exposure to various physical factors]. / Metabolicheskie reaktsii v chuvstvitel'nykh i dvigatel'nykh neironakh pri deistvii na organizm nekotorykh fizicheskikh faktorov.

A course of radiation of biologically active points of the guinea pig lumbosacral area has been performed by means of focused frequency-modulated and a continuous beam of the helium-neon laser, having various power density, as well as by means of an impulsive magnetic field. A comparative histoenzymatic analysis of sensitive neurons of the lumbar spinal nodes and of the caudal-mesenteric motor neurons has been carried out. The response of the metabolic processes in the sensitive neurons depends not so much on the type of action, as on adequacy of the parameters applied. The power density, frequency of impulse generation and time of application are important for characterization of the adequacy of the laser radiation. Peculiarities of the metabolic reactions in the sensitive and sympathetic neurons in response to the actions studied are discussed.