Biomedical subjects

J Debus

Publications and source records attributed to J Debus.

At least 73 records · Page 4Linked to original sources

PubMed2001

Tumor angiogenesis of low-grade astrocytomas measured by dynamic susceptibility contrast-enhanced MRI (DSC-MRI) is predictive of local tumor control after radiation therapy.

PURPOSE: To assess regional cerebral blood volume (rCBV) as a surrogate marker of angiogenesis in patients with low-grade fibrillary astrocytoma before radiation therapy and to correlate measured values with clinical outcome after fractionated stereotactic radiotherapy (FSRT). METHODS: Twenty-five patients with histologically proven fibrillary astrocytomas were examined using dynamic susceptibility contrast-enhanced MRI before radiotherapy. Radiotherapy was delivered to mean and median total doses of 60.9 and 60 Gy, respectively (range 55.8-66 Gy). During MRI for treatment planning, 55 T2*-weighted gradient echo images were acquired before, during, and after i.v. contrast-bolus injection. The acquired signal-time curves were converted into concentration-time curves. By normalization to an arterial input function, absolute and relative rCBV values were calculated. Measured pretherapeutic rCBV data were correlated to outcome in terms of local control after FSRT. RESULTS: Mean pretherapeutic rCBV for astrocytomas was 6.5 +/- 3.7 ml/100 g tissue. Mean and median follow-up times were 47.8 and 52 months, respectively. Fifteen tumors recurred during the period, with a mean and median latency of 39.1 and 42 months, respectively. Tumors recurring earlier than 42 months after FSRT showed a higher pretreatment rCBV than tumors recurring later and tumors in continued local control (8.12 +/- 4.48 ml/100 g vs. 6.0 +/- 2.3 ml/100 g and 4.73 +/- 2.47 ml/100 g; p = 0.02 and p = 0.03). The respective ratios of tumor rCBV in early recurrent tumors to gray matter and white matter rCBV were 0.98 +/- 0.38 and 2.17 +/- 1.36 as compared with 0.79 +/- 0.14 and 1.44 +/- 0.29 in locally controlled tumors (p = 0.074 and p = 0.056). CONCLUSIONS: In fibrillary low-grade astrocytomas, a noninvasive assessment of angiogenesis as indicated by rCBV measurement was feasible. The present data suggest that high pretherapeutic angiogenic activity in low-grade astrocytomas indicates a subgroup of tumors at higher risk for early local recurrence or malignant transformation after FSRT.

Adult↗

PubMed2001

Fractionated stereotactically guided radiotherapy and radiosurgery in the treatment of functional and nonfunctional adenomas of the pituitary gland.

PURPOSE: We evaluated survival rates and side effects after fractionated stereotactically guided radiotherapy (SCRT) and radiosurgery in patients with pituitary adenoma. METHODS AND MATERIALS: Between 1989 and 1998, 68 patients were treated with FSRT (n = 63) or radiosurgery (n = 5) for pituitary adenomas. Twenty-six had functional and 42 had nonfunctional adenomas. Follow-up included CT/MRI, endocrinologic, and ophthalmologic examinations. Mean follow-up was 38.7 months. Seven patients received radiotherapy as primary treatment and 39 patients received it postoperatively for residual disease. Twenty-two patients were treated for recurrent disease after surgery. Mean total dose was 52.2 Gy for SCRT, and 15 Gy for radiosurgery. RESULTS: Overall local tumor control was 93% (60/65 patients). Forty-three patients had stable disease based on CT/MRI, while 15 had a reduction of tumor volume. After FSRT, 26% with a functional adenoma had a complete remission and 19% had a reduction of hormonal overproduction after 34 months' mean. Two patients with STH-secreting adenomas had an endocrinologic recurrence, one with an ACTH-secreting adenoma radiologic recurrence, within 54 months. Reduction of visual acuity was seen in 4 patients and partial hypopituitarism in 3 patients. None of the patients developed brain radionecrosis or radiation-induced gliomas. CONCLUSION: Stereotactically guided radiotherapy is effective and safe in the treatment of pituitary adenomas to improve local control and reduce hormonal overproduction.

Adenoma↗

PubMed2001

High efficacy of fractionated stereotactic radiotherapy of large base-of-skull meningiomas: long-term results.

PURPOSE: Large skull-base meningiomas are difficult to treat due to their proximity or adherence to critical structures. We analyzed the long-term results of patients with skull-base meningiomas treated by a new approach with high-precision fractionated stereotactic radiotherapy. PATIENTS AND METHODS: One hundred eighty-nine patients with benign meningiomas were treated with conformal fractionated stereotactic radiotherapy between 1985 and 1998. Patients were undergoing a course of radiotherapy either as primary treatment, following subtotal resection, or for recurrent disease. The median target volume was 52.5 mL (range, 5.2 to 370 mL). The mean radiation dose was 56.8 Gy (+/- 4.4 Gy). Follow-up examinations, including magnetic resonance imaging, were performed at 6-month intervals thereafter. RESULTS: The median follow-up period was 35 months (range, 3 months to 12 years). Overall actuarial survival for patients with World Health Organization (WHO) grade I meningiomas was 97% after 5 years and 96% after 10 years. Local tumor failure was observed in three of 180 patients with WHO grade I tumors and was significantly higher in two of nine patients with WHO grade II tumors. A volume reduction of more than 50% was observed in 26 patients (14%). Preexisting cranial nerve symptoms resolved completely in 28% of the patients. Clinically significant treatment-induced toxicity was seen in 1.6% of the patients. No treatment-related deaths occurred. CONCLUSION: The results of this study demonstrate that fractionated stereotactic radiotherapy is safe and effective in the therapy of subtotally resected or unresectable meningiomas. The overall morbidity and incidence subacute and late side effects of this conformal radiotherapy approach were low.

Adolescent↗

PubMed2001

Transient enlargement of contrast uptake on MRI after linear accelerator (linac) stereotactic radiosurgery for brain metastases.

PURPOSE/OBJECTIVE: With the increasing number of patients successfully treated with stereotactic radiosurgery for brain metastases, decision making after therapy based on follow-up imaging findings becomes more and more important. Magnetic resonance imaging (MRI) is the most sensitive means for follow-up studies. The objective of this study was to investigate the treatment outcome of our radiosurgery program and to describe the response of brain metastases to contrast-enhanced MRI after linear accelerator (linac) stereotactic radiosurgery and identify factors to distinguish among local control and local failure. METHODS AND MATERIALS: Using serial MRI, we followed the course of 87 brain metastases in 48 consecutive patients treated between September 1996 and November 1997 with linac-based radiosurgery with 15-MV photons. Treatment planning was performed on an MR data cube. For spherical metastases, radiosurgery was delivered using a 9 noncoplanar arc technique with circular-shaped collimators. For irregularly shaped targets, radiosurgery was delivered using a manually driven multi-leaf collimator with a leaf width of 1.5 mm projected to the isocenter. Median radiosurgery dose was 20 Gy prescribed to the 80% isodose. Together with whole brain radiotherapy (20 x 2 Gy, 5/w), a median radiosurgical dose of 15 Gy was delivered. Median follow-up was 8 (range 2--36) months. Factors influencing local control and survival rates were analyzed with respect to MRI response, and Kaplan-Meier curves were calculated. RESULTS: Actuarial local tumor control was 91% at one and two years. Patient survival at one and two years was 30% and 18%. Median survival was 9 months. During follow-up in 70 (81%) of the 87 treated metastases, the contrast-enhancing volumes on T1W images were stable or disappeared partly or completely. A transient enlargement of contrast-enhancing volumes was observed in 11 (12%) of the 87 lesions treated, while a progressive enlargement due to local treatment failure was observed in 6 (7%) of the 87 treated metastases. Younger age, early contrast onset after radiosurgery, and previous chemotherapy were associated with this transient enlargement of contrast-enhancing lesion volume. CONCLUSIONS: Linac-based radiosurgery is an effective, noninvasive, and safe treatment option for patients with brain metastases. A marked enlargement of the contrast-enhancing volume on T(1)-weighted MR images after radiosurgery is a sensitive predictor for, but not equivalent with, local failure. In as many as two-thirds of the cases with contrast enlargement in MRI follow-up, the contrast enlargement is transient with no need for further treatment. While some MRI findings are more likely if transient enlargement is present, a clear decision cannot be made based on MRI, and ultimately the clinical status dictates further action.

Analysis of Variance↗

PubMed2001

Three-dimensional accuracy and interfractional reproducibility of patient fixation and positioning using a stereotactic head mask system.

PURPOSE: Conformal radiotherapy in the head and neck region requires precise and reproducible patient setup. The definition of safety margins around the clinical target volume has to take into account uncertainties of fixation and positioning. Data are presented to quantify the involved uncertainties for the system used. METHODS AND MATERIALS: Interfractional reproducibility of fixation and positioning of a target point in the brain was evaluated by biplanar films. 118 film pairs obtained at 52 fractions in 4 patients were analyzed. The setup was verified at the actual treatment table position by diagnostic X-ray units aligned to the isocenter and by a stereotactic X-ray localization technique. The stereotactic coordinates of the treated isocenter, of fiducials on the mask, and of implanted internal markers within the patient were measured to determine systematic and random errors. The data are corrected for uncertainty of the localization method. RESULTS: Displacements in target point positioning were 0.35 +/- 0.41 mm, 1.22 +/- 0.25 mm, and -0.74 +/- 0.32 mm in the x, y, and z direction, respectively. The reproducibility of the fixation of the patient's head within the mask was 0.48 mm (x), 0.67 mm (y), and 0.72 mm (z). Rotational uncertainties around an axis parallel to the x, y, and z axis were 0.72 degrees, 0.43 degrees, and 0.70 degrees, respectively. A simulation, based on the acquired data, yields a typical radial overall uncertainty for positioning and fixation of 1.80 +/- 0.60 mm. CONCLUSIONS: The applied setup technique showed to be highly reproducible. The data suggest that for the applied technique, a safety margin between clinical and planning target volume of 1-2 mm along one axis is sufficient for a target at the base of skull.

Algorithms↗

PubMed2001

Stereotactic single-dose radiation therapy of liver tumors: results of a phase I/II trial.

PURPOSE: To investigate the feasibility and the clinical response of a stereotactic single-dose radiation treatment for liver tumors. PATIENTS AND METHODS: Between April 1997 and September 1999, a stereotactic single-dose radiation treatment of 60 liver tumors (four primary tumors, 56 metastases) in 37 patients was performed. Patients were positioned in an individually shaped vacuum pillow. The applied dose was escalated from 14 to 26 Gy (reference point), with the 80% isodose surrounding the planning target volume. Median tumor size was 10 cm(3) (range, 1 to 132 cm(3)). The morbidity, clinical outcome, laboratory findings, and response as seen on computed tomography (CT) scan were evaluated. RESULTS: Follow-up data could be obtained from 55 treated tumors (35 patients). The median follow-up period was 5.7 months (range, 1.0 to 26.1 months; mean, 9.5 months). The treatment was well tolerated by all patients. There were no major side effects. Fifty-four (98%) of 55 tumors were locally controlled after 6 weeks at the initial follow-up based on the CT findings (22 cases of stable disease, 28 partial responses, and four complete responses). After a dose-escalating and learning phase, the actuarial local tumor control rate was 81% at 18 months after therapy. A total of 12 local failures were observed during follow-up. So far, the longest local tumor control is 26.1 months. CONCLUSION: Stereotactic single-dose radiation therapy is a feasible method for the treatment of singular inoperable liver metastases with the potential of a high local tumor control rate and low morbidity.

Adult↗

PubMed2001

[Radiotherapy planning for paraspinal tumors with CT-myelography].

BACKGROUND AND AIM: Artifacts due to metal implants are an important problem in diagnostic radiology and radiotherapy planning in tumors such as chordoma of the spine. A strict differentiation between target and radiosensitive structures e.g. spinal cord is absolutely essential for high-dose radiotherapy. Up to now CT and MRI techniques have provided only limited image quality in such situations. We introduce an approach to facilitate segmentation by using the technique of CT-myelography for radiation treatment. PATIENT AND METHOD: A 48-year-old woman with multiple inoperable relapses of a chordoma in the lumbar spine and extensive metal instrumentation in this area was given to radiotherapy using IMRT-technique (intensity modulated). MRI- and CT-planning images did not allow differentiation between myelon, cauda equina, dural sac and tumor. In this situation we performed a CT-myelography with the patient in treatment position. RESULT: CT-myelographic images enabled precise differentiation between myelon, cauda equina and intraspinal tumor. A substantial improvement of the segmentation of the spinal cord was obtained. There was no compression of the dural sac along the spine. This information provided the basis for a precise radiotherapy planning in IMRT-technique. CONCLUSION: In situations where CT- and MRI-techniques are not able to generate precise images which allow differentiation between tumor, myelon and cauda equina because of metal artifacts, CT-myelography is a promising technique which may help the diagnostic radiologist and radiation oncologist in planning radiotherapy.

Humans↗

PubMed2001

[Late radiation changes after small volume radiosurgery of the rat brain. Measuring local cerebral blood flow and histopathological studies].

BACKGROUND: The goal of this study was to investigate late effects following stereotactic single fraction and small volume irradiation on cerebral blood flow and histologic alterations in the rat brain parenchyma. MATERIAL AND METHODS: 66 Copenhagen rats, separated into eleven groups of six animals each received single doses of 20, 30, 40, 50 and 100 Gy using a 15 MV linear accelerator. Six rats served as controls. Two cylindrical collimators of 2 mm and 3 mm aperture were used. The diameters of the spherical 80% isodose were 3.7 and 4.7 mm, respectively (Table 1). Irradiation was applied to a predefined area in the right frontal lobe. 19 months after irradiation local cerebral blood flow (LCBF) was measured by the autoradiographic method in one animal of each dose group between 20 and 50 Gy. 9 and 19 months after irradiation, half of the animals of each group were sacrificed for brain histology. All animals irradiated with 100 Gy were sacrificed 7 months after irradiation. RESULTS: An increase of local cerebral blood flow was measured in brain structures within the 80% isodose in animals irradiated with 50 Gy (Figure 3) compared to the contralateral hemisphere. Measurements close to necrotic areas showed a strong decrease of local cerebral blood flow (Figure 1). A volume increase of the irradiated hemisphere was seen after 19 months (Figure 2). The histologic examination after 19 months showed necrotic areas in the 30-50 Gy groups (Figure 4b) but not in the 20 Gy groups (Figure 4c). The animals who received 100 Gy demonstrated brain necrosis within 9 months after irradiation (Figure 4a). At both points in time the groups irradiated with the 3-mm collimator showed more pronounced histomorphologic and functional changes compared to the groups irradiated with the 2-mm collimator. CONCLUSION: Alterations of the local cerebral blood flow were measured as a late effect after single dose irradiation. The alterations of the local cerebral blood flow could be explained by the histomorphologic changes of the blood vessels. Using a semi-quantitative classification a dose, time and volume dependence for the endpoint radionecrosis was seen.

Animals↗

PubMed2001

[Stereotactic irradiation of liver metastases].

PURPOSE: A number of minimal-invasive methods have been developed for the treatment of non-resectable liver metastases. A focused high dose can be delivered to a liver tumor with sparing of surrounding normal liver tissue using non-invasive stereotactic techniques. METHODS: Sixty-six metastases were treated stereotactically in 43 patients during a phase 2 trial. RESULTS: There were no major side effects observed. The actuarial local control was 82% after 18 months. The median actuarial survival was 24 months. However, there was a significantly improved survival in patients without additional extrahepatic tumor manifestation at the time of treatment compared to those, who were treated in palliative intention (87% vs. 24% after 18 months, p = 0.001 (log-rank). CONCLUSION: Stereotactic single dose irradiation is a non-invasive and safe treatment option for patients with inoperable liver metastases. Phase III studies will further evaluate this new approach.

Actuarial Analysis↗

PubMed2001

[Magnetic resonance-guided therapy with focused ultrasound. Non-invasive surgery of breast carcinoma?].

Magnetic resonance guided focused ultrasound surgery (MRgFUS) has the potential to become an important therapy modality in the adjuvant, neoadjuvant or palliative cancer treatment. All ultrasound accessible regions are possible target areas, especially breast tumors. Ultrasound propagation is well predictable. The ultrasound energy can be focused to a defined spot through the intact skin, and temperatures of 60 degrees C to 85 degrees C can be induced locally for a few seconds that instantaneously necrose biological tissues, while sparing surrounding healthy tissue. In addition, MRI is sensitive to temperature allowing for online monitoring of the temperature focus. In this work we demonstrate our Heidelberg experiments from basic research and animal studies towards the clinical realization of MRgFUS in breast cancer patients. The most important of these experiments involved sheep as an appropriate model for the human breast. A new therapy setup is designated to treat human breast patients in a clinical 1.5 T MRI scanner. While the therapies have been successful so far without any side effects, the future clinical role of noninvasive MRgFUS has to be defined by clinical studies.

Animals↗

PubMed2001

[High resolution MR-venography of cerebral arteriovenous malformations].

PURPOSE: The purpose of this study was to evaluate the diagnostic potential of a high resolution MR venography technique in patients with cerebral arteriovenous malformations (AVM). A high-resolution 3D gradient echo sequence was used with a long echo time TE to obtain venous information down to sub-pixel sized vessel diameters of several hundred microns. The method is based on the paramagnetic property of deoxyhemoglobin and the resulting developing phase difference between veins and brain parenchyma at long echo times which leads to signal cancellation. The reconstructed venograms were compared with TOF-MR angiography using qualitative and quantitative criteria with the conventional DSA serving as the reference gold standard. METHODS: In 17 patients with angiographically proven cerebral AVM the method indicates its potential in clinical applications. Venography was able to detect all AVM whereas TOF-MRA failed in three patients. In the delineation of venous drainage patterns MR venography was superior to TOF-MRA, however, as expected the method detected only about half of the main feeding arteries. Due to susceptibility artifacts at air/tissue boundaries or interference with paramagnetic hemosiderin, MR venography was limited with respect to the delineation of the exact nidus sizes and shapes in ten patients with AVM located close to the skull base or in patients having suffered from previous bleeding. RESULTS: Although the visualization of draining veins represents an important prerequisite in the surgical and radiosurgical treatment planning of cerebral AVM, there exist limitations of the technique in regions where strong induced static field inhomogeneities are present. CONCLUSIONS: Due to its high sensitivity the method may be of special importance in the early detection and assessment of small AVM which are difficult to diagnose with other MR methods.

Adolescent↗

PubMed2001

Postoperative fluid-attenuated inversion recovery MR imaging of cerebral gliomas: initial results.

Fluid-attenuated inversion-recovery (FLAIR) imaging has shown to be a valuable imaging modality in the assessment of intra-axial brain tumors; however, no data are available about the role of this technique in the clinically important postoperative stage. The purpose of this study was to evaluate the diagnostic potential of FLAIR MR imaging in residual tumor after surgical resection of cerebral gliomas. Fifteen patients with residual cerebral gliomas were examined within the first 18 days after partial surgical resection of cerebral gliomas. The imaging protocol included T1-weighted spin echo, T2- and proton-density-weighted fast spin echo, and FLAIR imaging with identical slice parameters. T1 and FLAIR were repeated after contrast media application. Detection and delineation of residual tumor were the primary parameters of the image analysis. Additionally, the influence of image artifacts on the image interpretation was assessed. On FLAIR images residual signal abnormalities at the border of the resection cavities were observed in all patients, whereas T2- and T1-weighted images present residual abnormalities in 13 of 15 and 10 of 15 patients, respectively. The FLAIR imaging was found to be superior to conventional imaging sequences in the delineation of these changes and comparable to contrast enhanced T1-weighted imaging in the delineation of residual enhancing lesions. Because of protein cell components and blood byproducts within the resection cavity, FLAIR imaging was unable to suppress the cerebrospinal fluid (CSF) in 4 patients. After the decomposition of proteins and blood, CSF could again be completely suppressed and residual or recurrent tumors were clearly identified. Our preliminary study has shown that FLAIR may be a valuable diagnostic modality in the early postoperative MR imaging after resection of cerebral gliomas due to its better delineation of residual pathologic signal at the border of the resection cavity. It should therefore be integrated into the early and/or intraoperative MR imaging protocol.

Adolescent↗

PubMed2001

Radiotherapy for advanced adenoid cystic carcinoma: neutrons, photons or mixed beam?

PURPOSE: To compare retrospectively radiotherapy with neutrons, photons, and a photon/neutron mixed beam in patients with advanced adenoid cystic carcinoma of the head and neck. Local control, survival, distant failure, and complications were analyzed. MATERIALS AND METHODS: Between 1983 and 1995, 75 patients with inoperable, recurrent, or incompletely resected adenoid cystic carcinoma of the head and neck received radiotherapy that consisted of either fast 14.1 MV DT neutrons (median dose 16 neutron Gy), linac-based photon irradiation (median dose 64 photon Gy), or both (median dose 8 neutron Gy and 32 photon Gy). Follow-up ranged from 1 to 160 months (median 51 months), and the surviving patients had a minimum follow-up of 3 years at the time of analysis. RESULTS: The actuarial 5-year local control was 75% for neutrons, and 32% for both mixed beam and photons (P = 0.015, log-rank). This advantage for neutrons in local control was not transferred to significant differences in survival (P > 0.1). The survival is dictated by the tumor diseases due to distant metastases occurring in 29 (39%) of the 75 patients. Positive lymph nodes were the only significant factor (P = 0.001) associated with the development of distant metastases although negative lymph nodes did not predict absence of distant metastases, but predicted a delay of occurrence. In multivariate analysis postoperative radiotherapy (P = 0.003) and small tumor size (P = 0.01) were associated with high local control, while primary therapy (P = 0.006) and negative lymph nodes (P = 0.01) were associated with longer survival. While acute toxicity was similar in all three radiotherapy groups, severe late grade 3 and 4 toxicity tended to be more prevalent (P > 0.1) with neutrons (19%) than with mixed beam (10%) and photons (4%). CONCLUSION: Fast neutron radiotherapy provides higher local control rates than a mixed beam and photons in advanced, recurrent or not completely resected adenoid cystic carcinoma of the major and minor salivary glands. Neutron radiotherapy can be recommended in patients with bad prognosis with gross residual disease (R2), with unresectable tumors, or inoperable tumors. The type of radiation does not impact survival, which is dominated by the high number of distant metastases.

Adult↗

PubMed2001

MR monitoring of focused ultrasound surgery in a breast tissue model in vivo.

The objective of this study was to investigate MRI methods for monitoring focused ultrasound surgery (FUS) of breast tumors. To this end, the mammary glands of sheep were used as tissue model. The tissue was treated in vivo with numerous single sonications which covered extended target volumes by employing a scanning technique. The ultrasound focus position was controlled by online temperature mapping based on the temperature dependence of the relaxation time T(1). This approach proved to be reliable and offers thus an alternative to proton resonance frequency methods, whose application is hampered in fatty tissues. FUS-induced tissue changes were visible on T(2)- as well as on pre- and post-contrast T(1)-weighted images. According to our initial experience, noninvasive MRI-guided FUS of breast tumors is feasible.

Adipose Tissue↗

PubMed2001

Partial irradiation of the brain.

Late radiation injury is the main dose-limiting factor for radiotherapy of tumors of the central nervous system (CNS). Clinical experience as well as analyses of complication data, both for brain necrosis and for changes in neuroimaging after radiosurgery, suggest a pronounced volume effect in the brain. However, the relationships of dose and volume to complications after irradiation of lesions in the brain have yet to be quantitatively assessed. The quantification of volume effects and the modeling of normal tissue response to partial organ irradiation of the brain are particularly demanding because of the highly differentiated and complex structure of the brain and the variety of endpoints after radiotherapy for CNS diseases. This article summarizes the existing clinical data that demonstrate a volume effect in the brain and the current state of knowledge regarding the modeling of complications following partial irradiation of the brain.

Brain↗

PubMed2001

Treatment planning for heavy ion radiotherapy: clinical implementation and application.

The clinical implementation and application of a novel treatment planning system (TPS) for scanned ion beams is described, which is in clinical use for carbon ion treatments at the German heavy ion facility (GSI). All treatment plans are evaluated on the basis of biologically effective dose distributions. For therapy control, in-beam positron emission tomography (PET) and an online monitoring system for the beam intensity and position are used. The absence of a gantry restricts the treatment plans to horizontal beams. Most of the treatment plans consist of two nearly opposing lateral fields or sometimes orthogonal fields. In only a very few cases a single beam was used. For patients with very complex target volumes lateral and even distal field patching techniques were applied. Additional improvements can be achieved when the patient's head is fixed in a tilted position, in order to achieve sparing of the organs at risk. In order to test the stability of dose distributions in the case of patient misalignments we routinely simulate the effects of misalignments for patients with critical structures next to the target volume. The uncertainties in the range calculation are taken into account by a margin around the target volume of typically 2-3 mm, which can, however, be extended if the simulation demonstrates larger deviations. The novel TPS developed for scanned ion beams was introduced into clinical routine in December 1997 and was used for the treatment planning of 63 patients with head and neck tumours until July 2000. Planning strategies and methods were developed for this tumour location that facilitate the treatment of a larger number of patients with the scanned heavy ion beam in a clinical setting. Further developments aim towards a simultaneous optimization of the treatment field intensities and more effective procedures for the patient set-up. The results demonstrate that ion beams can be integrated into a clinical environment for treatment planning and delivery.

Brain Neoplasms↗

PubMed2001

Improving chemoradiotherapy in rectal cancer.

The optimal management of rectal cancer remains a major challenge for oncologists. The treatment of stage II/III rectal cancer has historically been associated with a high risk of local recurrence and poor survival, which led to the development of adjuvant treatments in the hope of improving outcomes. The approach to adjuvant therapy for rectal cancer currently varies widely between Europe and the U.S. Postoperative adjuvant chemoradiation is the standard of care in the U.S. In contrast, in Europe, because there is a greater emphasis placed on preoperative imaging, meticulous surgical technique, and accurate pathologic reporting of the circumferential or radial margin, preoperative treatment (radiotherapy and chemoradiation) is used widely. The aims of preoperative radiotherapy and chemoradiation are to facilitate a curative resection (R0) and to increase the chance of performing sphincter-sparing procedures, and, therefore, to improve both survival and quality of life. This article reviews the clinical trials that led to these diverging standards of care. An interesting new approach in chemoradiation is the use of the oral fluoropyrimidine capecitabine as a combination partner for radiotherapy. Preclinical studies have demonstrated that the combination of capecitabine and radiotherapy has highly enhanced antitumor activity. This is most likely attributable to the upregulation of thymidine phosphorylase (the rate-limiting enzyme needed to convert capecitabine to 5-fluorouracil [5-FU]) in tumor cells following radiotherapy. A phase I study has consequently been performed to establish a feasible chemoradiotherapy combination. Capecitabine has the potential to replace bolus or continuous infusion 5-FU as the standard treatment for rectal cancer and offers a potentially enhanced therapeutic ratio. Oral chemotherapy has the additional advantage of simplifying chemoradiation and providing a treatment that is more appealing to patients.

Administration, Oral↗

PubMed2001

Tumor cytotoxicity in vivo and radical formation in vitro depend on the shock wave-induced cavitation dose.

Local tumor therapy using focused ultrasonic waves may become an important treatment option. This technique exploits the ability of mechanical waves to induce thermal and nonthermal effects noninvasively. The cytotoxicity to cultured cells and biological tissues in vivo that results from exposure to ultrasonic shock waves is considered to be a nonthermal effect that is partly a consequence of ultrasound-induced cavitation. Cavitation is defined as the formation of bubbles during the negative wave cycle; their subsequent oscillation and/or violent implosion can affect surrounding structures. To investigate cavitational effects in cells and tissues, defined cavitation doses must be applied while ideally holding all other potential ultrasound parameters constant. The application of independent cavitation doses has been difficult and has yielded little knowledge about quantitative cavitation-tissue interactions. By using a special shock-wave pulse regimen and laser optical calibration in this study, we were able to control the cavitation dose independently of other physical parameters such as the pressure amplitudes, and averaged acoustic intensity. We treated Dunning prostate tumors (subline R3327-AT1) transplanted into Copenhagen rats with shock waves at three cavitation dose levels and then determined the tumor growth delay and the histopathological changes. All of the treated animals exhibited a significant tumor growth delay compared to the controls. Higher cavitation doses were associated with a greater delay in the growth of the tumor and more severe effects on tumor histopathology, such as hemorrhaging, tissue disruption, and necrosis. In vitro, the cavitation dose level correlated with the amount of radical formation. We concluded that the process of acoustic cavitation was responsible; higher cavitation doses caused greater effects in tumors both in vivo and in vitro. These findings may prove important in local tumor therapy and other applications of ultrasound such as ultrasound-mediated drug delivery.

Animals↗