Klaus Herfarth

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.

Stereotactic single-dose radiotherapy of stage I non–small-cell lung cancer (NSCLC)

PURPOSE The treatment of early-stage lung cancers is a primary domain of thoracic surgery, leading to persuasive results. In patients with medical contraindications, radiotherapy is an alternative, although with considerably worse outcome. Radiotherapy is associated with the risk of severe acute side effects and a permanent decrease of lung function. By the introduction of an extracranial stereotactic treatment technique, the amount of normal tissue in the high-dose region can be reduced, allowing the performance of single-dose treatment with high, biologically effective doses. METHODS AND MATERIALS Between October 1998 and May 2001, 10 patients with histologically confirmed Stage I non-small-cell lung cancer were treated with stereotactic single-dose radiotherapy. A self-developed stereotactic frame was used for patient positioning and navigation. Total doses applied ranged from 19 to 26 Gy. After treatment, regular CT-based follow-up was performed. RESULTS During a median follow-up period of 14.9 months, the tumors in 8 of 10 patients were locally controlled. The actuarial overall survival was 80% and 64%, respectively, 12 and 24 months after therapy. Actuarial local recurrence-free survival reached 88.9% and 71.1%, respectively. Therapy-related perifocal normal-tissue reaction occurred in 70% of all treated patients, although no major clinical symptoms were seen. In 5 patients, systemic metastases were found during follow-up; 1 patient developed suspect mediastinal lymph nodes. CONCLUSION Stereotactic single-fraction radiotherapy is a feasible, safe, and effective procedure for the treatment of Stage I non-small-cell lung cancer. It promises high local control with a reduced overall treatment time. However, further investigation in a larger patient collective with extended follow-up is necessary.

EXTRACRANIAL STEREOTACTIC RADIATION THERAPY: SET-UP ACCURACY OF PATIENTS TREATED FOR LIVER METASTASES

PURPOSE Patients with liver metastases might benefit from high-dose conformal radiation therapy. A high accuracy of repositioning and a reduction of target movement are necessary for such an approach. The set-up accuracy of patients with liver metastases treated with stereotactic single dose radiation was evaluated. METHODS AND MATERIALS Twenty-four patients with liver metastases were treated with single dose radiation therapy on 26 occasions using a self-developed stereotactic frame. Liver movement was reduced by abdominal pressure. The effectiveness was evaluated under fluoroscopy. CT scans were performed on the planning day and directly before treatment. Representative reference marks were chosen and the coordinates were calculated. In addition, the target displacement was quantitatively evaluated after treatment. RESULTS Diaphragmal movement was reduced to median 7 mm (range: 3-13 mm). The final set-up accuracy of the body was limited to all of median 1.8 mm in latero-lateral direction (range: 0.3-5.0 mm) and 2.0 mm in anterior-posterior direction (0.8-3.8 mm). Deviations of the body in cranio-caudal direction were always less than the thickness of one CT slice (<5 mm). However, a repositioning was necessary in 16 occasions. The final target shift was median 1.6 mm (0.2-7.0 mm) in latero-lateral and 2.3 mm in anterior-posterior direction (0.0-6.3 mm). The median shift in cranio-caudal direction was 4.4 mm (0.0-10.0 mm). CONCLUSIONS In patients with liver metastases, a high set-up accuracy of the body and the target can be achieved. This allows a high-dose focal radiotherapy of these lesions. However, a control CT scan should be performed directly before therapy to confirm set-up accuracy and possibly prompt necessary corrections.

NONINVASIVE PATIENT FIXATION FOR EXTRACRANIAL STEREOTACTIC RADIOTHERAPY

PURPOSE To evaluate the setup accuracy that can be achieved with a novel noninvasive patient fixation technique based on a body cast attached to a recently developed stereotactic body frame during fractionated extracranial stereotactic radiotherapy. METHODS AND MATERIALS Thirty-one CT studies (> or = 20 slices, thickness: 3 mm) from 5 patients who were immobilized in a body cast attached to a stereotactic body frame for treatment of paramedullary tumors in the thoracic or lumbar spine were evaluated with respect to setup accuracy. The immobilization device consisted of a custom-made wrap-around body cast that extended from the neck to the thighs and a separate head mask, both made from Scotchcast. Each CT study was performed immediately before or after every second or third actual treatment fraction without repositioning the patient between CT and treatment. The stereotactic localization system was mounted and the isocenter as initially located stereotactically was marked with fiducials for each CT study. Deviation of the treated isocenter as compared to the planned position was measured in all three dimensions. RESULTS The immobilization device can be easily handled, attached to and removed from the stereotactic frame and thus enables treatment of multiple patients with the same stereotactic frame each day. Mean patient movements of 1.6 mm+/-1.2 mm (laterolateral [LL]), 1.4 mm+/-1.0 mm (anterior-posterior [AP]), 2.3 mm+/-1.3 mm (transversal vectorial error [VE]) and < slice thickness = 3 mm (craniocaudal [CC]) were recorded for the targets in the thoracic spine and 1.4 mm+/-1.0 mm (LL), 1.2 mm+/-0.7 mm (AP), 1.8 mm+/-1.2 mm (VE), and < 3 mm (CC) for the lumbar spine. The worst case deviation was 3.9 mm for the first patient with the target in the thoracic spine (in the LL direction). Combining those numbers (mean transversal VE for both locations and maximum CC error of 3 mm), the mean three-dimensional vectorial patient movement and thus the mean overall accuracy can be safely estimated to be < or = 3.6 mm. CONCLUSION The presented combination of a body cast and head mask system in a rigid stereotactic body frame ensures reliable noninvasive patient fixation for fractionated extracranial stereotactic radiotherapy and may enable dose escalation for less radioresponsive tumors that are near the spinal cord or otherwise critically located while minimizing the risk of late sequelae.

ASSESSMENT OF FOCAL LIVER REACTION BY MULTIPHASIC CT AFTER STEREOTACTIC SINGLE-DOSE RADIOTHERAPY OF LIVER TUMORS

PURPOSE To characterize and quantitatively assess focal radiation reactions in the liver after stereotactic single-dose radiotherapy for liver malignancies. METHODS AND MATERIALS A total of 131 multiphasic CT scans were performed in 36 patients before and after stereotactic radiotherapy for liver tumors. The examination protocol included a nonenhanced scan and contrast-enhanced scans at different times after contrast injection. The volume of the reaction was determined in each scan and the threshold dose calculated using the dose-volume histogram of the treatment plan. RESULTS Every patient showed a focal radiation reaction on at least one follow-up examination. In 74% of the posttherapeutic scans, a sharply demarcated hypodense area surrounded the treated tumor in the nonenhanced scans. The reaction occurred at a median of 1.8 months (range 1.2-4.6) after radiotherapy. The median threshold dose was 13.7 Gy (range 8.9-19.2). The threshold dose strongly correlated with the time of detection after therapy (r = 0.7). Radiologically, three reaction types were found on the enhanced scans: type 1, portal-venous phase: hypodense and late phase: isodense; type 2, portal-venous phase: hypodense and late phase: hyperdense; and type 3, portal-venous phase: isodense/hyperdense and late phase: hyperdense. Type 1 or 2 reactions were observed significantly earlier than type 3 (p <0.05). The median threshold dose for type 1 or 2 reactions was significantly lower than for type 3 (p <0.05). The reaction volume decreased with longer follow-up (2-4 months: median 40% of initial volume). The reaction types shifted with follow-up: 58% were of type 1 at the initial manifestation and 58% were of type 3 at the next examination thereafter. CONCLUSION A focal radiation reaction occurs after stereotactic single-dose therapy in the liver. The volume of the reaction decreases and changes its radiologic appearance during follow-up. This reaction has to be differentiated from recurrent tumor.

Helical tomotherapy. Experiences of the first 150 patients in Heidelberg.

Background and Purpose:Helical tomotherapy was introduced into clinical routine at the Department of Radiation Oncology, University Hospital of Heidelberg, Germany, in July 2006. This report is intended to describe the experience with the first 150 patients treated with helical tomotherapy. Patient selection, time effort, handling of daily image guidance with megavoltage (MV) CT, and quality of radiation plans shall be assessed.Patients and Methods:Between July 2006 and May 2007, 150 patients were treated with helical tomotherapy in the University Hospital of Heidelberg. Mean age was 60 years with a minimum of 30 years and a maximum of 85 years. 79 of these patients received radiotherapy as a part of multimodal treatment pre- or postoperatively, 17 patients received treatment as a combined radiochemotherapy. 76% were treated with curative intent. Radiotherapy sites were central nervous system (n = 7), head and neck (n = 28), thoracic (n = 37), abdominal (n = 58) and skeletal system (n = 20). Most common tumor entities were prostate cancer (n = 28), breast cancer (n = 17), gastrointestinal tumors (n = 19), pharyngeal carcinoma (n = 14), lymphoma (n = 13), metastatic disease (bone n = 14, liver n = 6, lung n = 4, lymph node n = 2), sarcoma (n = 8), malignant pleural mesothelioma (n = 5), ovarian cancer treated with whole abdominal irradiation (n = 4), lung cancer (n = 3), skin malignancies (n = 3), chordoma (n = 2), meningioma (n = 2), one ependymoma and one medulloblastoma treated with craniospinal axis irradiation (n = 2), and others (n = 4). Nine patients were treated with single-fraction radiosurgery, nine with image-guided spinal reirradiation, and twelve patients were treated at multiple targets simultaneously. A pretreatment MV-CT scan was performed in 98.2% of the 3,026 fractions applied. After matching with the kilovoltage planning CT, corrections for translations and rotation around longitudinal axis (roll) were done.Results:Mean time on table was 24.8 min for the mentioned tumor entities with fractionated radiation, mean treatment time 10.7 min. Mean correction vector after MV-CT registration was 6.9 mm. With helical tomotherapy it was possible to achieve highly conformal dose distributions for targets of all sizes and multiple targets within one procedure. Image guidance with MV-CT allowed daily position correction and safe and precise treatment application. This was feasible even if the desired immobilization was not possible due to obesity, claustrophobia, pain, or neurologic or orthopedic impairment.Conclusion:Helical tomotherapy and daily image guidance with MV-CT could fast be introduced into daily clinical routine. This technique allows precise intensity-modulated radiotherapy (IMRT) in standard cases and offers new treatment options in a huge variety of difficult cases.Hintergrund und Ziel:Die helikale Tomotherapie wurde im Juli 2006 in der radioonkologischen Abteilung der Universitätsklinik Heidelberg in die klinische Routine eingeführt. Diese Arbeit soll die Erfahrungen der ersten 150 mit helikaler Tomotherapie behandelten Patienten beschreiben. Die Selektion der Patienten, Zeitaufwand, täglicher Gebrauch der Bildführung mittels Megavolt-(MV-)CT sowie die Qualität der Bestrahlungspläne sollen untersucht werden.Patienten und Methodik:Zwischen Juli 2006 und Mai 2007 wurden 150 Patienten mittels helikaler Tomotherapie im Universitätsklinikum Heidelberg behandelt. Das mittlere Alter betrug 60 Jahre mit einem Minimum von 30 Jahren und einem Maximum von 85 Jahren. 79 der Patienten erhielten eine Radiotherapie als Teil einer multimodalen Behandlung prä- oder postoperativ, 17 Patienten wurden einer kombinierten Radiochemotherapie unterzogen. 76% wurden in kurativer Absicht therapiert. Orte der Radiotherapieapplikation waren zentrales Nervensystem (n = 7), Kopf/Hals (n = 28), Thorax (n = 37), Abdomen (n = 58) und Skelettsystem (n = 20). Die häufigsten Tumorentitäten waren Prostatakarzinome (n = 28), Mammakarzinome (n = 17), gastrointestinale Tumoren (n = 19), Pharynxkarzinome (n = 14), Lymphome (n = 13), Metastasen (ossär n = 14, hepatisch n = 6, pulmonal n = 4, Lymphknoten n = 2), Sarkome (n = 8), maligne Pleuramesotheliome (n = 5), Ovarialkarzinome, die mittels Ganzabdomenbestrahlung behandelt wurden (n = 4), Bronchialkarzinome (n = 3), Hautmalignome (n = 3), Chordome (n = 2), Meningeome (n = 2), ein Ependymom und ein Medulloblastom, welche mittels Neuroachsenbestrahlung behandelt wurden, sowie andere Histologien (n = 4). Neun Patienten erhielten eine radiochirurgische Therapie in einer einzelnen Fraktion, neun Patienten eine bildgeführte spinale Rebestrahlung, und zwölf Patienten wurden an multiplen Targets gleichzeitig behandelt. Ein prätherapeutisches MV-CT wurde in 98,2% der 3 026 applizierten Fraktionen durchgeführt, und nach dem Matching wurden hierauf basierend Korrekturen für Translationen und Rotation um die Longitudinalachse („roll“) durchgeführt.Ergebnisse:Für die beschriebenen Tumorentitäten betrug die durchschnittliche Zeit auf dem Bestrahlungstisch bei fraktionierter Bestrahlung 24,8 min, die durchschnittliche Nettobehandlungszeit 10,7 min. Der mittlere Korrekturvektor nach MV-CT-Matching lag bei 6,9 mm. Mittels helikaler Tomotherapie war es möglich, hochkonformale Dosisverteilungen für Zielvolumina aller Größen oder multiple Zielvolumina in einer einzelnen Bestrahlungsprozedur zu erzielen. Dabei erlaubte die tägliche Bildführung mittels MV-CT eine sichere Positionskorrektur und präzise Durchführung der Therapie. Dies war auch möglich, wenn eine gewünschte Immobilisation aufgrund von Platzangst, Adipositas, Schmerzen oder neurologischer oder orthopädischer Begleiterkrankungen nicht vorgenommen werden konnte.Schlussfolgerung:Helikale Tomotherapie und tägliche Bildführung mittels MV-CT konnten schnell und erfolgreich in die klinische Routine eingeführt werden. Diese Technik ermöglicht die präzise und schonende Behandlung von Standardfällen mittels intensitätsmodulierter Strahlentherapie (IMRT) und eröffnet neue Behandlungsoptionen für schwierige Fälle.

Stereotactic single-dose radiotherapy (radiosurgery) of early stage nonsmall-cell lung cancer (NSCLC).

The clinical results after stereotactic single‐dose radiotherapy of nonsmall‐cell lung cancer (NSCLC) stages I and II were evaluated.

Differentiation of radiation necrosis from tumor progression using proton magnetic resonance spectroscopy.

Abstract. We report on a young woman who was treated by stereotactic radiotherapy for recurrence of an initially resected low-grade astrocytoma. MRI follow-up examination 7 months after radiotherapy showed a gadolinium-DTPA-enhancing mass lesion indicative of high-grade tumor progression. This assumption was also supported by positron emission tomography with [2-18F]fluoro-2-deoxy-D–glucose (FDG-PET). In contrast, proton MR spectroscopy (1H-MRS) indicated radiation necrosis, which was confirmed histopathologically in surgical specimens. Subsequent follow-up examinations up to 19 months after surgery showed no evidence of tumor recurrence.

A Multi-institutional Clinical Trial of Rectal Dose Reduction via Injected Polyethylene-Glycol Hydrogel During Intensity Modulated Radiation Therapy for Prostate Cancer: Analysis of Dosimetric Outcomes

PURPOSE To characterize the effect of a prostate-rectum spacer on dose to rectum during external beam radiation therapy for prostate cancer and to assess for factors correlated with rectal dose reduction. METHODS AND MATERIALS Fifty-two patients at 4 institutions were enrolled into a prospective pilot clinical trial. Patients underwent baseline scans and then were injected with perirectal spacing hydrogel and rescanned. Intensity modulated radiation therapy plans were created on both scans for comparison. The objectives were to establish rates of creation of ≥ 7.5 mm of prostate-rectal separation, and decrease in rectal V70 of ≥ 25%. Multiple regression analysis was performed to evaluate the associations between preinjection and postinjection changes in rectal V70 and changes in plan conformity, rectal volume, bladder volume, bladder V70, planning target volume (PTV), and postinjection midgland separation, gel volume, gel thickness, length of PTV/gel contact, and gel left-to-right symmetry. RESULTS Hydrogel resulted in ≥7.5-mm prostate-rectal separation in 95.8% of patients; 95.7% had decreased rectal V70 of ≥ 25%, with a mean reduction of 8.0 Gy. There were no significant differences in preinjection and postinjection prostate, PTV, rectal, and bladder volumes. Plan conformities were significantly different before versus after injection (P=.02); plans with worse conformity indexes after injection compared with before injection (n=13) still had improvements in rectal V70. In multiple regression analysis, greater postinjection reduction in V70 was associated with decreased relative postinjection plan conformity (P=.01). Reductions in V70 did not significantly vary by institution, despite significant interinstitutional variations in plan conformity. There were no significant relationships between reduction in V70 and the other characteristics analyzed. CONCLUSIONS Injection of hydrogel into the prostate-rectal interface resulted in dose reductions to rectum for >90% of patients treated. Rectal sparing was statistically significant across a range of 10 to 75 Gy and was demonstrated within the presence of significant interinstitutional variability in plan conformity, target definitions, and injection results.

Helical Tomotherapy as a New Treatment Technique for Whole Abdominal Irradiation

Purpose:To describe a new intensity-modulated radiotherapy (IMRT) technique using helical tomotherapy for whole abdominal irradiation (WAI) in patients with advanced ovarian cancer.Material and Methods:A patient with radically operated ovarian cancer FIGO stage IIIc was treated in a prospective clinical trial with WAI to a total dose of 30 Gy in 1.5-Gy fractions as an additional therapy after adjuvant platinum-based chemotherapy. The planning target volume (PTV) included the entire peritoneal cavity. PTV was adapted according to breathing motion as detected in a four-dimensional respiratory-triggered computed tomography (4D-CT). Inverse treatment planning was done with the Hi-Art tomotherapy planning station. Organs at risk (OARs) were kidneys, liver, bone marrow, spinal cord, thoracic and lumbosacral vertebral bodies, and pelvic bones. Daily control of positioning accuracy was performed with megavoltage computed tomography (MV-CT).Results:Helical tomotherapy enabled a very homogeneous dose distribution with excellent sparing of OARs and coverage of the PTV (V90 of 93.1%, V95 of 86.9%, V105 of 1.9%, and V110 of 0.01%). Mean liver dose was 21.57 Gy and mean kidney doses were 9.75 Gy and 9.14 Gy, respectively. Treatment could be performed in 18.1 min daily and no severe side effects occurred.Conclusion:Helical tomotherapy is feasible and fast for WAI. Tomotherapy enabled excellent coverage of the PTV and effective sparing of liver, kidneys and bone marrow.Ziel:Beschreibung der ersten klinischen Erfahrungen mit einer helikalen Tomotherapie als neuartiges Therapieverfahren für eine intensitätsmodulierte Ganzabdomenbestrahlung in der adjuvanten Therapie des fortgeschrittenen Ovarialkarzinoms.Material und Methodik:Eine Patientin mit Ovarialkarzinom im Stadium FIGO IIIc wurde im Rahmen einer prospektiven klinischen Studie nach radikaler Operation und sechs Zyklen adjuvanter platinhaltiger Chemotherapie zusätzlich mit einer Ganzabdomenbestrahlung mittels helikaler Tomotherapie behandelt. Die Gesamtdosis betrug 30 Gy mit einer wöchentlichen Fraktionierung von 5 × 1,5 Gy. Das Planungszielvolumen (PTV) umfasste die gesamte Peritonealhöhle unter Einschluss der paraaortalen und pelvinen Lymphabflusswege. Das Ausmaß des Zielvolumens wurde der Atembewegung auf Basis einer atemgetriggerten vierdimensionalen Computertomographie (4D-CT) angepasst. Es wurde mit dem Hi-Art-tomotherapy-Planungssystem invers geplant. Als Risikoorgane wurden Nieren, Leber, Rückenmark, Brustwirbelsäule, Lendenwirbelsäule und knöchernes Becken definiert. Die korrekte Patientenpositionierung wurde mittels Megavolt-Computertomographie (MV-CT) täglich kontrolliert.Ergebnisse:Mittels helikaler Tomotherapie konnten eine homogene Dosisverteilung, eine exzellente Schonung der Risikoorgane sowie eine ausgezeichnete Erfassung des PTV erreicht werden (V90: 93,1%, V95: 86,9%, V105: 1,9%, V110: 0,01%). Die mediane Dosis an der Leber betrug 21,57 Gy und an den Nieren jeweils 9,75 Gy und 9,14 Gy. Die tägliche Bestrahlungsdauer lag bei 18,1 min. Es traten keine schweren Nebenwirkungen CTC (Common Toxicity Criteria) Grad 3 oder 4 auf.Schlussfolgerung:Die Ganzabdomenbestrahlung mittels helikaler Tomotherapie ist machbar und in der klinischen Routine einsetzbar. Mit der helikalen Tomotherapie konnte eine exzellente Erfassung des PTV bei gleichzeitig sehr guter Schonung von Leber, Nieren und Knochenmark erreicht werden.