Karl Henne

Radiosurgery followed by planned observation in patients with one to three brain metastases.

OBJECTIVE To analyze the role of radiosurgery alone in patients with brain metastases. There were three specific study goals: 1) to determine whether survival of patients selected for this treatment approach can be predicted successfully by use of the recursive partitioning analysis classification defined by the Radiation Therapy Oncology Group; 2) to evaluate local control; and 3) to identify risk factors of cerebral failure. METHODS A total of 101 patients with Karnofsky Performance Scale scores of at least 50 and up to three brain metastases, each 3 cm or less in maximum diameter, were treated with radiosurgery alone. Survival, local control, distant brain freedom from progression (FFP), and overall brain FFP were evaluated according the method of Kaplan and Meier. Risk factors for survival and overall brain FFP were analyzed using the Cox model. RESULTS Median survival was 13.4 months, 9.3 months, and 1.5 months for patients in recursive partitioning analysis Classes 1, 2, and 3, respectively (P < 0.0001). At 1 year, local control, distant brain FFP, and overall brain FFP were 91, 53, and 51%, respectively. An interval greater than 2 years between diagnosis of the primary tumor and diagnosis of brain metastases and the presence of a single brain metastasis were associated with significantly higher overall brain FFP. CONCLUSION Recursive partitioning analysis classification successfully predicted survival. Radiosurgery alone yielded high local control. Overall brain FFP was highest in patients with an interval greater than 2 years between primary diagnosis and diagnosis of a single brain metastasis.

Salvage Lymph Node Dissection with Adjuvant Radiotherapy for Nodal Recurrence of Prostate Cancer

PURPOSE We evaluated the impact of salvage lymph node dissection with adjuvant radiotherapy in patients with nodal recurrence of prostate cancer. By default, nodal recurrence of prostate cancer is treated with palliative antihormonal therapy, which causes serious side effects and invariably leads to the development of hormone refractory disease. MATERIALS AND METHODS A total of 47 patients with nodal recurrence of prostate cancer based on evidence of (11)C-choline/(18)F-choline ((18)F-fluorethylcholine) positron emission tomography-computerized tomography underwent primary (2 of 52), secondary (45 of 52), tertiary (4 of 52) and quaternary (1 of 52) salvage lymph node dissection with histological confirmation. Of 52 salvage lymph node dissections 27 were followed by radiotherapy. Biochemical response was defined as a prostate specific antigen less than 0.2 ng/ml after salvage therapy. The Kaplan-Meier method, binary logistic regression and Cox regression were used to analyze survival as well as predictors of biochemical response and clinical progression. RESULTS Mean prostate specific antigen at salvage lymph node dissection was 11.1 ng/ml. A mean of 23.3 lymph nodes were removed per salvage lymph node dissection. Median followup was 35.5 months. Of 52 salvage lymph node dissections 24 resulted in complete biochemical response followed by 1-year biochemical recurrence-free survival of 71.8%. Gleason 6 or less (OR 7.58, p = 0.026), Gleason 7a/b (OR 5.91, p = 0.042) and N0 status at primary therapy (OR 8.01, p = 0.011) were identified as independent predictors of biochemical response. Gleason 8-10 (HR 3.5, p = 0.039) as a preoperative variable, retroperitoneal positive lymph nodes (HR 3.76, p = 0.021) and incomplete biochemical response (HR 4.0, p = 0.031) were identified as postoperative predictors of clinical progression. Clinical progression-free survival was 25.6% and cancer specific survival was 77.7% at 5 years. CONCLUSIONS Based on (11)C/(18)F-choline positron emission tomography-computerized tomography as a diagnostic tool, salvage lymph node dissection is feasible for the treatment of nodal recurrence of prostate cancer. Most patients experience biochemical recurrence after salvage lymph node dissection. However, a specific population has a lasting complete prostate specific antigen response.

Retrobulbar irradiation for thyroid-associated orbitopathy: double-blind comparison between 2.4 and 16 Gy

PURPOSE Retrobulbar irradiation is used as a standard therapy for thyroid-associated orbitopathy. The evidence of its effectiveness is, however, scarce. Doses from 2.5 to 20 Gy have been recommended. METHODS Forty-three patients with active thyroid-associated orbitopathy were irradiated with 2.4 Gy and 43 with 16 Gy. Five measures of outcome were used: (1) appearance of the eye region, documented with photographs; (2) Hertel exophthalmometry; (3) range of vertical eye movements; (4) eye muscle thickness (sum of three MRI sections across the eight rectus eye muscles); and (5) complaints, indicated on a visual analog scale. RESULTS At 3 and 6 months after irradiation, no difference between 2.4 and 16 Gy was found in any of the five outcome measures (p between 0.099 and 0.993; Kruskal-Wallis test, Holm correction). Most outcome measures were slightly, but not significantly, improved in both the 2.4 and the 16 Gy groups. Patient complaints had improved significantly in both groups and the eye muscle thickness was significantly reduced in the 2.4 Gy group after 6 months. CONCLUSION The lack of a difference between 2.4 and 16 Gy is compatible with four different interpretations: (1) the irradiation could be ineffective; (2) the maximal effect could be already reached at 2.4 Gy; (3) the maximal effect could lie between 2.4 and 16 Gy; and (4) the effect could increase beyond a threshold of >or=16 Gy. From general experience with inflammatory disease, the last two possibilities are unlikely; only the first two interpretations carry some probability. Although the design of the study did not allow a distinction between these two possibilities, we conclude that retrobulbar irradiation for thyroid-associated orbitopathy should not exceed 2.4 Gy.

Detection of local recurrent prostate cancer after radical prostatectomy in terms of salvage radiotherapy using dynamic contrast enhanced-MRI without endorectal coil.

PurposeTo evaluate the value of dynamic contrast enhanced Magnetic Resonance Imaging (DCE-MRI) without endorectal coil (EC) in the detection of local recurrent prostate cancer (PC) after radical prostatectomy (RP).Material and methodsThirty-three patients with recurrent PC underwent DCE-MRI without EC before salvage radiotherapy (RT). At median 15 (mean 16±4.9, range 12–27) months after completion of RT all patients showed complete biochemical response. Additional follow up post RT DCE-MRI scans were available. Prostate specific antigen (PSA) levels at the time of imaging were correlated to the imaging findings.ResultsIn 22/33 patients (67%) early contrast enhancing nodules were detected in the post-prostatectomy fossa on pre-RT DCE-MRI images. The average pre-RT PSA level of the 22 patients with positive pre-RT DCE-MRI findings was significantly higher (mean, 0.74±0.64 ng/mL) compared to the pre-RT PSA level of the 11 patients with negative pre-RT DCE-MRI (mean, 0.24±0.13 ng/mL) (p<0.001). All post-RT DCE-MRI images showed complete resolution of initial suspicious lesions. A pre-RT PSA cut-off value of ≥0.54 ng/ml readily predicted a positive DCE-MRI finding.ConclusionsThis is the first study that shows that DCE-MRI without EC can detect local recurrent PC with an estimated accuracy of 83% at low PSA levels. All false negative DCE-MRI scans were detected using a PSA cut-off of ≥0.54 ng/mL.

Stereotactic fractionated radiotherapy for Klatskin tumours

BACKGROUND AND PURPOSE In spite of various efforts perihilar cholangiocellular carcinoma (Klatskin tumour) has still a bad prognosis. The treatment of patients with inoperable Klatskin tumours by stereotactic fractionated radiotherapy (SFRT) was analysed retrospectively. PATIENTS, METHODS AND MATERIALS: In our department 13 patients were treated for Klatskin tumours by SFRT (32-56 Gy, 3 x 4 Gy/week) from 1998 to 2008. The treatment technique was developed from stereotactic body frame radiotherapy to image guided (IGRT) stereotactic radiotherapy with control of patient positioning by cone beam computer tomography (CBCT). 6/13 patients received additional chemotherapy before or after SFRT. RESULTS A median survival of 33.5 (6.6-60.4) months after diagnosis was reached by SFRT. The median time of freedom from tumour progression was 32.5 (6.1-60.4, last patient died without tumour progression) months. The therapy was tolerated very well. Nausea was the most common side effect. 5/13 patients suffered from recurrent cholangitis caused and enhanced by the primary tumour and drainages or stents in the bile ducts. CONCLUSIONS In the context of reaching local control being still the main problem of Klatskin tumour patients, SFRT seems to be a very promising method for the treatment of these tumours.

Quality of life and sexual functioning in endometrial cancer survivors

OBJECTIVE Recent evidence suggests equivalent efficacy in terms of local control for adjuvant vaginal brachytherapy (VBT) compared to external beam radiotherapy after surgery in patients with intermediate-high endometrial cancer. The objective of this study is to compare the quality of life (QoL) and sexual function of women with endometrial cancer that were treated with either surgery alone or surgery in combination with postoperative VBT. METHODS Women were interviewed at least 5 years after initial treatment for endometrial cancer. QoL was evaluated by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and the cervical cancer module, CX-24. Sexual function was evaluated by using the Female Sexual Function Index (FSFI). Eligible women had early stage disease, were currently disease-free, and had undergone surgery and adjuvant VBT, but neither external beam radiotherapy nor systemic treatment. This study group were then compared using univariate and multivariate analyses with an age-matched control group comprising of endometrial cancer patients without adjuvant VBT. RESULTS Fifty-five patients (29 surgery plus VBT and 26 surgical controls without VBT) were included for analysis. With respect to QoL including, e.g., physical, role, emotional and social functioning and likewise in terms of sexual function univariate and multivariate analyses did not show significant differences between patients with VBT and the controls without VBT of any of the outcome measures. CONCLUSION Adjuvant VBT after surgery does not seem to have a significant impact on quality of life and sexual function in endometrial cancer survivors.

3 Tesla multiparametric MRI for GTV-definition of Dominant Intraprostatic Lesions in patients with Prostate Cancer – an interobserver variability study

PurposeTo evaluate the interobserver variability of gross tumor volume (GTV) - delineation of Dominant Intraprostatic Lesions (DIPL) in patients with prostate cancer using published MRI criteria for multiparametric MRI at 3 Tesla by 6 different observers.Material and methods90 GTV-datasets based on 15 multiparametric MRI sequences (T2w, diffusion weighted (DWI) and dynamic contrast enhanced (DCE)) of 5 patients with prostate cancer were generated for GTV-delineation of DIPL by 6 observers. The reference GTV-dataset was contoured by a radiologist with expertise in diagnostic imaging of prostate cancer using MRI. Subsequent GTV-delineation was performed by 5 radiation oncologists who received teaching of MRI-features of primary prostate cancer before starting contouring session. GTV-datasets were contoured using Oncentra Masterplan® and iplan® Net. For purposes of comparison GTV-datasets were imported to the Artiview® platform (Aquilab®), GTV-values and the similarity indices or Kappa indices (KI) were calculated with the postulation that a KI > 0.7 indicates excellent, a KI > 0.6 to < 0.7 substantial and KI > 0.5 to < 0.6 moderate agreement. Additionally all observers rated difficulties of contouring for each MRI-sequence using a 3 point rating scale (1 = easy to delineate, 2 = minor difficulties, 3 = major difficulties).ResultsGTV contouring using T2w (KI-T2w = 0.61) and DCE images (KI-DCE = 0.63) resulted in substantial agreement. GTV contouring using DWI images resulted in moderate agreement (KI-DWI = 0.51). KI-T2w and KI-DCE was significantly higher than KI-DWI (p = 0.01 and p = 0.003). Degree of difficulty in contouring GTV was significantly lower using T2w and DCE compared to DWI-sequences (both p < 0.0001). Analysis of delineation differences revealed inadequate comparison of functional (DWI, DCE) to anatomical sequences (T2w) and lack of awareness of non-specific imaging findings as a source of erroneous delineation.ConclusionsUsing T2w and DCE sequences at 3 Tesla for GTV-definition of DIPL in prostate cancer patients by radiation oncologists with knowledge of MRI features results in substantial agreement compared to an experienced MRI-radiologist, but for radiotherapy purposes higher KI are desirable, strengthen the need for expert surveillance. DWI sequence for GTV delineation was considered as difficult in application.

Endoscopic ultrasound-guided brachytherapy of head and neck tumours. A new procedure for controlled application.

Brachytherapy is an established procedure in primary and in recurrent cancer. We perform afterloading brachytherapy during general anaesthesia. The target organ is punctured with hollow needles which are loaded with 192iridium via remote control. The depth and number of needles depend on tumour extension. In the interdisciplinary approach of our departments, this method has been improved and supplied by B-scan ultrasound control. Needles are positioned under continuous ultrasonographic guidance, and adjacent structures (e.g. the carotid artery) are localized ultrasonographically. Thus violation of the large vessels is avoided and the exact position of the needles within the tumour is improved. In this paper, we report results on 22 patients suffering from recurrent carcinoma of the head and neck following surgery and curative radiation, and 17 patients with first onset of cancer. We did not observe any severe complications such as haemorrhage, osteomyelitis, or dyspnoea. The only side-effect was temporary oedema, sometimes associated with a short-term increase of pain. No systemic side-effects occurred. The method is described and results from both patient groups are reported in detail. We conclude from our data that ultrasonographically-controlled endoscopic brachytherapy is a valuable procedure in locally-advanced primary, and in recurrent head and neck cancer.

Abteilungs- und Patientenmanagement in der Strahlenheilkunde

Hintergrund und Ziel:Die Arbeit im Bereich der Strahlentherapie ist hauptsächlich dadurch geprägt, dass täglich eine Vielzahl z.T. komplexer Arbeitsabläufe bewältigt und dabei hohe Sicherheitsanforderungen erfüllt werden müssen. Dieser Sachverhalt und stetig wachsender ökonomischer Druck zwingen uns, neue Strategien zu entwickeln, die unsere Arbeitsabläufe optimieren und deren Zuverlässigkeit und Sicherheit garantieren. Da es relativ wenige strahlentherapeutische Einrichtungen gibt und das Augenmerk bislang hauptsächlich auf den beschleunigernahen Systemen (Bestrahlungsplanung, Beschleunigersteuerung usw.) lag, stehen derzeit seitens der Industrie nur wenige Systeme zur Verfügung, die geeignet wären, auch die ökonomischen, organisatorischen und administrativen Bedürfnisse der Strahlentherapie zu unterstützen.Methodik:Im Rahmen der Baumaßnahme „neue Strahlenklinik“ am Universitätsklinikum Freiburg wurde von den Funktionsbereichen Klinische und Administrative Informatik und Medizinische Physik in enger Zusammenarbeit mit dem ärztlichen Personal ein umfassendes Konzept zur Steuerung und Organisation einer strahlentherapeutischen Einrichtung entwickelt. Das Konzept wurde im Zuge des Neubaues und des damit verbundenen HBFG-Verfahrens (Hochschulbauförderungsgesetz) durch die Deutsche Forschungsgemeinschaft begutachtet und mit Bundesmitteln in vollem Umfang unterstützt.Ergebnisse und Schlussfolgerung:Voraussetzung für das Ziel, ein homogenes und umfassendes Management einer Strahlenklinik zu betreiben, war die direkte Verbindung der beschleunigernahen Seite mit der organisatorischen/administrativen Umgebung. Die dadurch entstandene gemeinsame Datenbasis und Konsistenz schafften Transparenz und ermöglichten uns erstmals die umfassende organisatorische und EDV-technische Kontrolle aller Arbeitsabläufe. Nach nunmehr 2 Jahren Vollbetrieb und Umsetzung zahlreicher Teilprojekte stehen wir unmittelbar vor dem film- und papierlosen Digitalbetrieb.Background and Purpose:The activities in radiotherapy are mainly affected by numerous partly very complex operational procedures which have to be completed while high safety requirements have to be fulfilled. This fact and steadily increasing economic pressure are forcing us to develop new strategies which help us to optimize our operational procedures and assure their reliability. As there are not so many radiotherapeutic institutions and the main focus, up to now, was mainly stressed on the acceleration systems (radiation planning, acceleration control), only few industrial systems are available which could also support the economic, organizational and administrative needs of radiotherapy.Methods:During the building operations for the “new clinic for radiotherapy” at the University Hospital Freiburg, Germany, the staff of the clinical and administrative information and the medical physicists developed, in close cooperation with the physicians, a comprehensive concept to control and organize a radiotherapeutic institution. This concept was examined during the construction phase of the new clinic and the adjoined HBFG (“Hochschulbauförderungsgesetz”) process by the “Deutsche Forschungsgemeinschaft” and financed totally by federal funds.Results and Conclusion:The precondition for the goal to operate a homogeneous and comprehensive management of a clinic for radiotherapy was the direct connection of the acceleration area with the organizational/administrative surrounding. The thus developed common basic dates and consistence created transparency and allowed us for the first time to control all operational procedures by EDV-technical means. After 2 years full-time operation and implementation of numerous particular projects we are now ready for film- and paperless digital work.

Zweitmalignome nach Therapie des Morbus Hodgkin : das Freiburger Kollektiv 1940 bis 1991

AIM To quantify the risk of second malignancies in patients with Hodgkins disease treated at the Department of Radiotherapy, University Clinic Freiburg, with the object of comparing this risk with the international experience and as a contribution to the discussion about future treatment. PATIENTS AND METHODS Second malignancies were reviewed in 1,588 patients treated for Hodgkins disease between 1940 and 1991. Treatment consisted of involved or extended field radiotherapy as a single modality or in combination with chemotherapy. Before the early 1970s, chemotherapy used (sequential) monodrug regimens. The mean follow-up was 8.3 years. The cumulative risk was calculated using the Kaplan-Meier method and related to the risk of a normal population taken from epidemiological data of the National Cancer Institute. An estimate of radiation dose at the site of origin of the second malignancy was obtained from representative measurements employing an Alderson phantom. RESULTS After 5, 10, 15 and 20 years the cumulative risk for all malignancies was 1.5%, 4.2%, 9.4% and 21%, respectively; for solid tumors it came to 1.2%, 3.1%, 7.9% and 19%; for non-Hodgkin lymphoma (NHL) the risk amounted to 0.1%, 0.9%, 1.4% and 1.9%; and for leukemia it was 0.1%, 0.3%, 0.6% and 0.6%. For the same time points the relative risk for all malignancies was calculated to be 1.1, 1.4, 1.8 and 2.5; for solid tumors it came to 1.0, 1.1, 1.6 and 2.5; for NHL it amounted to 3.3, 11.8, 9.3 and 8.0; and for leukemia it was 3.3, 3.1, 3.4 and 2.1. For combinations of radiotherapy and chemotherapy the risk for second malignancies was highest in patients receiving ABVD any time during their treatment. 51% of the second malignancies were located infield, 22% at the field border and 27% outfield. In those cases for which the cause of death was known, Hodgkins disease accounted for 79% followed by second malignancies accounting for 8%. The results obtained in Freiburg fell within the range reported in international publications. CONCLUSION The increased incidence of second malignancies in cured Hodgkins patients is along-term risk making regular follow-up mandatory. Although part of the second malignancies are unrelated to therapy, there is a need to carefully collect the data from patients treated according to new protocols in order to detect any changes in the number or kind of second malignancies in due time. This may well lead to a reassessment of therapeutic concepts.ZielDatenerhebung zur Frage des Zweitmalignomrisikos bei Patienten mit Morbus Hodgkin der Abteilung Strahlentherapie der Freiburger Universitätsklinik als Standortbestimmung im internationalen Vergleich und als Beitrag zur Diskussion neuer Therapiemodalitäten.Patienten und MethodikDie Krankenunterlagen von 1 588 Patienten der Behandlungsjahrgänge 1940 bis 1991 wurden hinsichtlich der Inzidenz von soliden Tumoren, Non-Hodgkin-Lymphomen und Leukämie nach Therapie des Morbus Hodgkin ausgewertet. Die mittlere Beobachtungszeit betrug 8,3 Jahre. Die Behandlungsmodalitäten umfaβ ten Strahlentherapie allein als “Involved”-oder “Extended-field”-Bestrahlung und kombinierte Strahlenchemotherapie, seit etwa 1970 als konsequente Polychemotherapie. Zur Ermittlung des relativen kumulativen Zweimalignomrisikos wurde das kumulative Risiko in Beziehung zu epidemiologischen Daten des National Cancer Institute gesetzt. Die Abschätzung der Strahlendosis am Entstehungsort der Zweitmalignome erfolgte nach Meβ ergebnissen am Alderson-Phantom.ErgebnisseDas kumulative Risiko betrug nach fünf, zehn, 15 bzw. 20 Jahren für alle Malignome 1,5%, 4,2%, 9,4% bzw. 21%, für solide Tumoren 1,2%, 3,1%, 7,9% bzw. 19%, für Non-Hodgkin-Lymphome 0,1%, 0,9%, 1,4% bzw. 1,9% und für Leukämie 0,1%, 0,3%, 0,6% bzw. 0,6%. Für die gleichen Zeiträume wurde das relative kumulative Risiko (RR) für alle Malignome mit 1,1,1,4,1,8 bzw. 2,5, für solide Tumoren mit 1,0,1,1,1,6 bzw. 2,5, für Non-Hodgkin-Lymphome mit 3,3,11,8, 9,3 bzw. 8,0 und für Leukämie mit 3,3,3,1, 3,4 bzw. 2,1 berechnet. Nach Kombination der Strahlentherapie mit einer konsequenten Polychemotherapie (seit ca. 1970) hatten die ABVD enthaltenden Kombinationstherapien bei Berücksichtigung der Primär- und Sekundärtherapie das höchste Zweitmalignomrisiko. Von den Zweitmalignomen entwickelten sich 51% im Bestrahlungsfeld, 22% am Feldrand und 27% auβ erhalb des Bestrahlungsfeldes. Unter den bekannten Todesursachen lag der Morbus Hodgkin mit 79% an erster Stelle, gefolgt von der Zweitmalignommortalität mit 8%. Insgesamt wichen die Freiburger Ergebnisse nicht entscheidend von den Ergebnissen bisher international veröffentlichter Publikationen ab.Schluβ folgerungDie erhöhte Inzidenz von Zweitmalignomen als Langzeitrisiko nach Therapie des Morbus Hodgkin ist in jedem Fall ein Grund, eine konsequente und praktisch permanente ärztliche Nachsorge zu fordern. Auch mit dem Vorbehalt, daβ nicht jedes Zweitmalignom notwendig der Therapie angelastet werden kann, ist sie ein Grund mehr, den Morbus Hodgkin in multizentrischen Therapiestudien zu behandeln, um möglichst rasch Änderungen im Charakter und in der Inzidenz der Zweitmalignome zu erfassen und gegebenenfalls das therapeutische Konzept zu korrigieren.AbstractAimTo quantify the risk of second malignancies in patients with Hodgkin’s disease treated at the department of radiotherapy, University Clinic Freiburg, with the object of comparing this risk with the international experience and as a contribution to the discussion about future treatment.Patients and MethodsSecond malignancies were reviewed in 1 588 patients treated for Hodgkin’s disease between 1940 and 1991. Treatment consisted of involved or extended field radiotherapy as a single modality or in combination with chemotherapy. Before the early 1970’s, chemotherapy used (sequential) monodrug regimens. The mean follow-up was 8.3 years. The cumulative risk was calculated using the Kaplan-Meier method and related to the risk of a normal population taken from enidemiological data of the National Cancer Institute. An estimate of radiation dose at the site of origin of the second malignancy was obtained from representative measurements employing an Alderson phantom.ResultsAfter 5, 10,15 and 20 years the cumulative risk for all malignancies was 1.5%, 4.2%, 9.4% and 21%, respectively; for solid tumors it came to 1.2%, 3.1%, 7.9% and 19%; for non-Hodgkin lymphoma (NHL) the risk amounted to 0.1%, 0.9%, 1.4% and 1.9%; and for leukemia it was 0.1%, 0.3%, 0.6% and 0.6%. For the same time points the relative risk for all malignancies was calculated to be 1.1,1.4,1.8 and 2.5; for solid tumors it came to 1.0,1.1,1.6 and 2.5; for NHL it amounted to 3.3,11.8, 9.3 and 8.0; and for leukemia it was 3.3, 3.1, 3.4 and 2.1. For combinations of radiotherapy and chemotherapy the risk for second malignancies was highest in patients receiving ABVD any time during their treatment. 51% of the second malignancies were located infield, 22% at the field border and 27% outfield. In those cases for which the cause of death was known, Hodgkin’s disease accounted for 79% followed by second malignancies accounting for 8%. The results obtained in Freiburg fell within the range reported in international publications.ConclusionThe increased incidence of second malignancies in cured Hodgkin’s patients is a long-term risk making regular follow-up mandatory. Although part of the second malignancies are unrelated to therapy, there is a need to carefully collect the data from patients treated according to new protocols in order to detect any changes in the number or kind of second malignancies in due time. This may well lead to a reassessment of therapeutic concepts.