Brigitte Hermann

Memory Function Before and After Whole Brain Radiotherapy in Patients With and Without Brain Metastases

PURPOSE To prospectively compare the effect of prophylactic and therapeutic whole brain radiotherapy (WBRT) on memory function in patients with and without brain metastases. METHODS AND MATERIALS Adult patients with and without brain metastases (n = 44) were prospectively evaluated with serial cognitive testing, before RT (T0), after starting RT (T1), at the end of RT (T2), and 6-8 weeks (T3) after RT completion. Data were obtained from small-cell lung cancer patients treated with prophylactic cranial irradiation, patients with brain metastases treated with therapeutic cranial irradiation (TCI), and breast cancer patients treated with RT to the breast. RESULTS Before therapy, prophylactic cranial irradiation patients performed worse than TCI patients or than controls on most test scores. During and after WBRT, verbal memory function was influenced by pretreatment cognitive status (p < 0.001) and to a lesser extent by WBRT. Acute (T1) radiation effects on verbal memory function were only observed in TCI patients (p = 0.031). Subacute (T3) radiation effects on verbal memory function were observed in both TCI and prophylactic cranial irradiation patients (p = 0.006). These effects were more pronounced in patients with above-average performance at baseline. Visual memory and attention were not influenced by WBRT. CONCLUSIONS The results of our study have shown that WBRT causes cognitive dysfunction immediately after the beginning of RT in patients with brain metastases only. At 6-8 weeks after the end of WBRT, cognitive dysfunction was seen in patients with and without brain metastases. Because cognitive dysfunction after WBRT is restricted to verbal memory, patients should not avoid WBRT because of a fear of neurocognitive side effects.

Intraoperative radiotherapy as a boost during breast-conserving surgery using low-kilovoltage X-rays: the first 5 years of experience with a novel approach.

PURPOSE Intraoperative radiotherapy (IORT) during breast-conserving surgery (BCS) has been recently introduced using different devices. We report the first 5 years of a single-center experience after introduction of a novel approach to deliver IORT as a tumor bed boost during BCS for breast cancer. METHODS AND MATERIALS A total of 155 breast cancers in 154 women (median age, 63 years; range, 30-83 years; T1/T2 = 100/55; N0/N+ = 108/47) were treated between February 2002 and December 2007 at the University Medical Center Mannheim, in whom IORT as tumor bed boost was applied using 50-kV X-rays (20 Gy) followed by 46-50 Gy whole-breast external-beam radiotherapy (EBRT). Chemotherapy, if indicated, was given before EBRT. The median interval between BCS plus IORT and EBRT was 40 days. Median follow-up was 34 months (maximum 80 months, 1 patient lost to follow-up). Overall survival and local relapse-free survival were calculated at 5 years using the Kaplan-Meier method. Seventy-nine patients were evaluated at 3-year follow-up for late toxicity according to the Late Effects in Normal Tissues-Subjective, Objective, Management, and Analytic system. RESULTS Ten patients died, 2 had in-breast relapse, and 8 developed distant metastases (5-year overall survival = 87.0%; 5-year local relapse-free survival = 98.5%). Grade 3 fibroses of the tumor bed were detected in 5% of the patients after 3 years. Skin toxicity was mild (telangiectases and hyperpigmentations in approximately 6% each). CONCLUSIONS Intraoperative radiotherapy as a tumor bed boost during BCS for breast cancer using low-kilovoltage X-rays followed by EBRT yields low recurrence and toxicity rates.

Optimization of dose distributions for adjuvant Locoregional radiotherapy of gastric cancer by IMRT

Background and Purpose: Locoregional relapse is a problem frequently encountered with advanced gastric cancer. Data from the randomized Intergroup trial 116 suggest effectiveness of adjuvant radiochemotherapy, albeit with significant toxicity. The potential of intensity-modulated radiotherapy (IMRT) to reduce toxicity by significantly reducing maximum and median doses to organs at risk while still applying sufficient dose to the target volume in the upper abdomen was studied. Patient and Methods: For a typical configuration of target volumes and organs, a step-and-shoot IMRT plan (eight beam orientations), developed as a class solution for treatment of tumors in the upper abdomen (Figures 1 to 3), a conventional plan, a combination of the conventional plan with a kidney-sparing boost plan, and a conventional plan with noncoplanar ap and pa fields for improved kidney sparing were compared with respect to coverage of target volume and dose to organs at risk with a dose of 45 Gy delivered as the median dose to the target volume. Results: When using the conventional three-dimensionally planned box techniques, the right kidney could be kept below tolerance, but median dose to the left kidney amounted to between 14.8 and 26.9 Gy, depending on the plan. IMRT reduced the median dose to the left kidney to 10.5 Gy, while still keeping the dose to the right kidney < 8 Gy. Liver was spared better with IMRT. Dose to the lungs was not significantly different, and dose to the spinal cord was higher (but well below tolerance) with IMRT. The dose distribution within the target volume was less homogeneous than for the conventional plans. With regard to target coverage, > 90% of prescription dose were delivered to > 90% of target volume with IMRT (Table 1). Conclusion: IMRT has the potential to deliver efficient doses to target volumes in the upper abdomen, while delivering dose to organs at risk in a more advantageous fashion than a conventional technique. For clinical implementation, the possibility of extensive organ motion in the upper abdomen has to be taken into account for treatment planning and patient positioning. The multitude of potential risks related to its application has to be the subject of thorough follow-up and further studies.Hintergrund und Ziel: Die adjuvante Therapie des fortgeschrittenen Magenkarzinoms wird kontrovers diskutiert. Der Intergroup- Trial 116 wies jedoch erstmals die prinzipielle Effizienz einer adjuvanten Radiochemotherapie nach. Des Weiteren stellt bei suffizienter strahlentherapeutischer Einfassung der Zielregion jedoch die Toxizität dieser Behandlungsstrategie ein Problem dar. Es wurde daher versucht, durch Einsatz der intensitätsmodulierten Strahlentherapie (IMRT) bei einem typischen Zielvolumen im Oberbauch die mediane und maximale Risikoorganbelastung bei vergleichbarer Zielvolumenabdeckung zu reduzieren. Patient und Methodik: Für eine typische Konfiguration von Zielvolumen und Risikoorganen wurden eine als „class solution“ entwickelte Acht-Felder-IMRT-Technik (Abbildungen 1 bis 3), ein konventioneller Plan, eine Kombination dieses konventionellen Plans mit einem nierenschonenden Boostplan und ein konventioneller Plan mit nonkoplanarer Ausrichtung von a.p. und p.a. Feld zur besseren Nierenschonung hinsichtlich Zielvolumeneinfassung und Belastung der Risikoorgane verglichen. Ergebnisse: Mit konventionellen Techniken konnte zwar die rechte Niere ausreichend geschont werden, die linke Niere wurde jedoch je nach Plan mit einer medianen Dosis zwischen 14,8 und 26,9 Gy belastet. IMRT reduzierte die mediane linksseitige Nierendosis auf 10,5 Gy, während die mediane rechtsseitige Nierendosis immer noch < 8 Gy gehalten werden konnte. Die Leberbelastung war bei IMRT ebenfalls reduziert. Die Lungendosen unterschieden sich nicht wesentlich. Die Rückenmarkdosis war bei IMRT höher als bei konventioneller Bestrahlung, jedoch deutlich unter der Toleranz. Die Dosisverteilung im Zielvolumen war bei IMRT inhomogener, auch mittels IMRT konnten zuverlässig > 90% der Verschreibungsdosis auf > 90% des Zielvolumens appliziert werden (Tabelle 1). Schlussfolgerung: IMRT moduliert die Belastung der Risikoorgane im Oberbauch gegenüber einer konventionell 3-D-geplanten Technik günstiger, sodass Ausschöpfung und Einhaltung der Organtoleranzen erleichtert werden. Bei der klinischen Implementierung muss die besondere Mobilität der Oberbauchorgane bei der Planung und der Patientenpositionierung berücksichtigt werden. Die zahlreichen technischen und biologischen Unwägbarkeiten der Anwendung der IMRT insbesondere in dieser Region erfordern die vorsichtige Implementierung, langfristige Nachbeobachtung und weitere Untersuchungen.

Acute neurocognitive impairment during cranial radiation therapy in patients with intracranial tumors

Background and PurposeThe objective of the current study was to evaluate the acute effects of cranial radiation therapy (CNS-RT) using different radiation doses (0, 1.8, 2, 3, ≥ 20 Gy) on cognitive function with special emphasis on memory. We assessed patients with and without intracranial tumors to distinguish between direct and indirect radiation effects on brain tissue.Materials and MethodsEighty-two patients were evaluated with neuropsychological testing before and acutely after radiotherapy (RT). Sixty-four patients received RT to the brain (55 with, 9 without intracranial tumor). Eighteen patients treated with RT to the breast served as controls.ResultsPatients with intracranial tumor demonstrated attention (19–38th percentile) and verbal memory scores (34–46th percentile) below the population average at baseline. The average Verbal Memory score was significantly different between patients with intracranial tumor and controls both at baseline (38th vs. 58th percentile) and after irradiation (27th vs. 52th percentile). Patients with preexisting peritumoral edema performed worse than patients without edema and controls. Radiation dose-related deficits were seen for working memory performance in patients with intracranial tumor.ConclusionOur data indicate no measurable impairment of cognitive functioning acutely after prophylactic cranial irradiation. Patients with intracranial tumor show a deterioration of almost all memory functions with a dose-dependent impairment in working memory. Patients with preexisting peritumoral brain edema show the strongest deterioration.ZusammenfassungHintergrund und ZielDie vorliegende Arbeit untersucht Akuteffekte der kraniellen Strahlentherapie (ZNS-RT) nach unterschiedlichen Bestrahlungsdosen (0, 1.8, 2, 3, ≥ 20 Gy) auf die kognitive Funktion unter besonderer Berücksichtigung des verbalen Gedächtnisses. Wir haben Patienten mit und ohne Hirntumor untersucht, um zwischen direkten und indirekten Bestrahlungseffekten auf das Hirngewebe zu unterscheiden.Patienten und Methodik82 Patienten wurden vor und unmittelbar nach Beginn der Radiotherapie (RT) neuropsychologisch untersucht. 64 Patienten wurden am ZNS bestrahlt (55 mit, 9 ohne Hirntumor). 18 Patientinnen, die an der Mamma bestrahlt wurden, dienten als Kontrollgruppe.ErgebnisseVor RT-Beginn lagen Aufmerksamkeitsleistungen (Prozentränge von 19–38) und verbale Gedächtnisleistungen (Prozentränge von 34–46) der Patienten mit Hirntumor unterhalb des Mittelwertes für die Normalbevölkerung (Tabellen 4, 5). Die durchschnittliche verbale Gedächtnisleistung der Patienten mit Hirntumor unterschied sich vor (Prozentrang 38 vs. 58) und nach RT (Prozentrang 27 vs. 52) signifikant von der der Kontrollgruppe (Abbildung 1). Patienten mit einem peritumoralen Hirnödem vor ZNS-RT zeigen schlechtere Leistungen als Patienten ohne Hirnödem und Kontrollpatienten (Abbildung 3). Bestrahlungsdosisabhängige Effekte wurden für das Arbeitsgedächtnis bei Patienten mit ZNS-Tumor beobachtet (Abbildung 2).SchlussfolgerungUnsere Daten zeigen keine messbaren kognitiven Beeinträchtigungen unmittelbar nach Beginn einer prophylaktischen Ganzhirnbestrahlung. Patienten mit Hirntumor zeigen eine Verschlechterung der verbalen Gedächtnisfunktionen und eine dosisabhängige Beeinträchtigung im Arbeitsgedächtnis. Patienten mit einem peritumoralen Hirnödem vor ZNS-RT zeigen die größten Veränderungen.

Clinical Implementation of Volumetric Intensity-Modulated Arc Therapy (VMAT) with ERGO++

Background and Purpose:Volumetric modulated arc therapy (VMAT) has the potential to deliver dose distributions comparable to the established intensity-modulated radiotherapy techniques for a multitude of target paradigms. Prior to implementing VMAT into their clinical routine in December 2008, the authors evaluated the dose calculation/delivery accuracy of 24 sample VMAT plans (prostate and anal cancer target paradigms) with film and ionization dosimetry. After the start of the clinical program, in vivo measurements with a rectal probe were performed.Material and Methods:The VMAT plans were generated by the treatment-planning system (TPS) ERGO++ (Elekta, Crawley, UK) and transferred to a phantom. Film dosimetry was performed with Kodak EDR2 films, and evaluated with dose profiles and γ-index analysis. Appropriate ionization chambers were used for absolute dose measurements in the phantom and for in vivo measurements. The ionization chamber was used with localization of the measurement volume based on positioning cone-beam computed tomography.Results:Plans were transferred from ERGO++ to the record and verify (R&V) system/linear accelerator (linac). The absolute dose deviations recorded with the ionization chamber were 1.74% ± 1.62% across both indications. The γ-index analysis of the film dosimetry showed no deviation > 3%/3 mm in the high-dose region. On in vivo measurements, a deviation between calculation and measurement of 2.09% ± 2.4% was recorded, when the chamber was successfully positioned in the high-dose region.Conclusion:VMAT plans can be planned and treated reproducibly in high quality after the commissioning of the complete delivery chain consisting of TPS, R&V system and linac. The results of the individual plan verification meet the commonly accepted requirements. The first in vivo measurements confirm the reproducible precision of the delivered dose during clinical treatments.ZusammenfassungHintergrund und Ziel:Die volumetrisch modulierte Arc-Therapie (VMAT) bietet die Möglichkeit, für einige Planparadigmata zur bisher etablierten intensitätsmodulierten Strahlentherapie vergleichbare Dosisverteilungen zu generieren. Vor der im Dezember 2008 erfolgten Einführung von VMAT in die eigene klinische Routine überprüften die Autoren Dosisberechnung und Bestrahlungsgenauigkeit anhand von 24 VMAT-Plänen (Anal- und Prostatakarzinomplanungsparadigmata) mittels Film- und Ionisationsdosimetrie. Erste Patientenbestrahlungen wurden mittels rektaler In-vivo-Dosimetrie verifiziert.Material und Methodik:Die VMAT-Pläne wurden mit dem Planungssystem ERGO++ (Elekta, Crawley, UK) generiert und in einem Phantom verifiziert. Filmdosimetrie wurde mittels Kodak-EDR2-Film, Dosisprofilen und der γ-Analyse realisiert. Geeignete Ionisationskammern wurden für absolute Dosismessungen im Phantom und für die In-vivo-Dosimetrie verwendet. Ein Cone-Beam-Computertomogramm wurde für die Lokalisation des Messvolumens der Ionisationskammer im Rektum verwendet.Ergebnisse:Die Pläne wurden durchgängig fehlerfrei von ERGO++ an das „record and verify“-(R&V-)System und an den Beschleuniger übertragen. Die mittlere Abweichung der Absolutdosimetrie betrug 1,74% ± 1,62%. Die γ-Index-Analyse der Filmdosimetrie zeigte keine Abweichung > 3%/3 mm im Hochdosisbereich. Die In-vivo-Messungen ergaben nach erfolgreicher Positionierung im Hochdosisbereich eine mittlere Abweichung zwischen berechneter und applizierter Dosis von 2,09% ± 2,4%.Schlussfolgerung:VMAT-Pläne können auf Basis der klinisch zugelassenen Kette aus Planungs-, R&V- und Bestrahlungssystem nach adäquater Kommissionierung reproduzierbar erzeugt und zuverlässig bestrahlt werden. Die Ergebnisse der Individualplanverifikation erfüllen die allgemein akzeptierten Bedingungen. Erste in vivo ermittelte Dosen bestätigen die Präzision der Dosisapplikation im klinischen Einsatz.

Can the Radiation Dose to CT-Enlarged but FDG-PET-Negative Inguinal Lymph Nodes in Anal Cancer Be Reduced?

Purpose:To investigate whether a dose reduction to CT-enlarged but FDG-PET-negative (([18F]-fluoro-2-deoxy-D-glucose positron emission tomography) inguinal lymph nodes in radiochemotherapy of anal cancer is safe.Patients and Methods:39 sequential patients with anal cancer (mean age 59 years [range: 37–86 years], median follow-up 26 months [range: 3–51 months]) receiving pretherapeutic FDG-PET were included. All patients were treated with combined radiochemotherapy including elective radiation of the inguinal lymph nodes with 36 Gy. In case of involvement (FDG-PET positivity defined as normalized SUV [standard uptake value] above Δ > 2.5 higher than blood pool), radiation dose was increased up to 50–54 Gy. Planning CT and PET results were compared for detectability and localization of lymph nodes. In addition, local control and freedom from metastases were analyzed regarding the lymph node status as determined by FDG-PET.Results:In the planning CTs, a total of 162 inguinal lymph nodes were detected with 16 in nine patients being suspicious. Only three of these lymph nodes in three patients were PET-positive receiving 50.4–54 Gy, whereas all other patients only received elective inguinal nodal irradiation. No recurrence in inguinal lymph nodes occurred, especially not in patients with CT-enlarged inguinal lymph nodes and elective irradiation only. Patients with PET-positive nodal disease had a higher risk of developing distant metastases (p = 0.045).Conclusion:Reduction of the irradiation dose to CT-enlarged but PET-negative inguinal lymph nodes in anal cancer seems not to result in increased failure rates.Ziel:Untersucht wurde, ob eine Reduktion der Bestrahlungsdosis auf im CT vergrößerte, aber PET-negative (Positronenemissionstomographie) inguinale Lymphknoten bei der kombinierten Radiochemotherapie des Analkarzinoms ohne Verschlechterung der Prognose möglich ist.Patienten und Methodik:39 Patienten mit Analkarzinom (median Alter 59 Jahre [37–86 Jahre]), mittlerer Nachsorgezeitraum 26 Monate [3–51 Monate]) mit einer prätherapeutischen PET-Untersuchung wurden in die Auswertung eingeschlossen (Tabelle 1). Alle Patienten erhielten eine kombinierte Radiochemotherapie einschließlich einer elektiven Bestrahlung der inguinalen Lymphknoten bis zu einer Dosis von 36 Gy, bei Befall (PET-positiv: normalisierter Uptakewert mehr als das 2,5fache höher als der gemessene Wert im Blutpool) wurde die Dosis auf 50–54 Gy aufgesättigt. Das Bestrahlungsplanungs-CT und die PET-Untersuchung wurden in Bezug auf Nachweisbarkeit und Lokalisation der Lymphknoten verglichen. Zusätzlich wurden die lokale Kontrolle und das metastasenfreie Überleben in Abhängigkeit vom im PET erhobenen Lymphknotenstatus ermittelt.Ergebnisse:In den Bestrahlungsplanungs-CTs wurden insgesamt 162 inguinale Lymphknoten detektiert; davon wurden 16 bei neun Patienten als suspekt eingestuft. Nur drei dieser suspekten inguinalen Lymphknoten bei drei Patienten waren PET-positiv und wurden mit 50,4–54 Gy bestrahlt (Abbildungen 1a und 1b), während alle anderen Patienten nur eine elektive Bestrahlung der Leisten mit 36 Gy erhielten (Tabellen 2a bis 2c). Keiner der Patienten entwickelte ein Rezidiv im Bereich der inguinalen Lymphknoten, insbesondere auch nicht die Patienten, die bei im CT vergrößerten Lymphknoten nur elektiv in den Leisten bestrahlt wurden. Patienten mit PET-positiven Lymphknoten hatten ein erhöhtes Risiko für Fernmetastasen (p = 0,045; Abbildung 2).Schlussfolgerung:Eine Reduktion der Bestrahlungsdosis bei im CT vergrößerten, aber PET-negativen inguinalen Lymphknoten scheint nicht mit einem erhöhten Rezidivrisiko einherzugehen.

Intraoperative Radiotherapy (IORT) as a Boost in Patients with Early-Stage Breast Cancer – Acute Toxicity

Background: We report on acute toxicities as well as the early cosmetic outcome of patients receiving intraoperative radiotherapy (IORT) followed by whole-breast radiotherapy (WBRT) compared to patients treated with standard WBRT alone. Patients and Methods: From 2/2002 until 2/2005, 84 breast cancer patients were treated with IORT during breast-conserving surgery (BCS) as a boost (20 Gy/50 kV X-rays) followed by WBRT. After wound healing, all IORT patients were treated with WBRT at a total dose of 46 Gy. For the purpose of comparison, 53 patients treated consecutively between 1/2003 and 12/2004 in our institution with BCS followed by WBRT at a total dose of 50-66 Gy, were analyzed. All patients had a defined followup schedule. Toxicities were prospectively documented using the CTC/EORTC Score. Cosmesis was evaluated after 6 months using a 1-4 score. Results: Treatment was well tolerated with no grade 3/4 acute toxicity. Rare adverse effects following IORT included wound healing problems (2%), erythema grade I-II (3%), palpable seroma (6%) and mastitis (2-4%). The number of patients with induration of the tumor bed was comparably low. Conclusion: IORT with the IntrabeamTM system applied as a boost during BCS, followed by 46 Gy WBRT, exerts similar acute toxicity as standard WBRT. Further follow-up is needed to assess long-term toxicity and efficacy.

Intrafraction motion of the prostate during an IMRT session: a fiducial-based 3D measurement with Cone-beam CT.

BackgroundImage-guidance systems allow accurate interfractional repositioning of IMRT treatments, however, these may require up to 15 minutes. Therefore intrafraction motion might have an impact on treatment precision. 3D geometric data regarding intrafraction prostate motion are rare; we therefore assessed its magnitude with pre- and post-treatment fiducial-based imaging with cone-beam-CT (CBCT).Methods39 IMRT fractions in 5 prostate cancer patients after 125I-seed implantation were evaluated. Patient position was corrected based on the 125I-seeds after pre-treatment CBCT. Immediately after treatment delivery, a second CBCT was performed. Differences in bone- and fiducial position were measured by seed-based grey-value matching.ResultsFraction time was 13.6 ± 1.6 minutes. Median overall displacement vector length of 125I-seeds was 3 mm (M = 3 mm, Σ = 0.9 mm, σ = 1.7 mm; M: group systematic error, Σ: SD of systematic error, σ: SD of random error). Median displacement vector of bony structures was 1.84 mm (M = 2.9 mm, Σ = 1 mm, σ = 3.2 mm). Median displacement vector length of the prostate relative to bony structures was 1.9 mm (M = 3 mm, Σ = 1.3 mm, σ = 2.6 mm).Conclusiona) Overall displacement vector length during an IMRT session is < 3 mm.b) Positioning devices reducing intrafraction bony displacements can further reduce overall intrafraction motion.c) Intrafraction prostate motion relative to bony structures is < 2 mm and may be further reduced by institutional protocols and reduction of IMRT duration.

Radiotherapy of the Neuroaxis for Palliative Treatment of Leptomeningeal Carcinomatosis

Background: Leptomeningeal carcinomatosis occurs in about 5% of solid tumors and may seriously compromise quality of life. Aim of the present study was to evaluate the feasibility of craniospinal irradiation with and without intrathecal chemotherapy and its efficacy with regard to symptom palliation and survival. Patients and Methods: 16 patients (mean age 46 years; nine breast cancers, five lung cancers, one renal cell cancer, one tumor of unknown primary site) with leptomeningeal carcinomatosis occurring after a median interval from primary tumor diagnosis of 5 months (0–300 months) received craniospinal irradiation between October 1995 and May 2000. The median total dose was 36 Gy (à 1.6–2.0 Gy). Ten patients were additionally treated with intrathecal methotrexate (15 mg per cycle, 2–8 cycles). Results: Median survival was 12 weeks, 8 weeks after radiotherapy alone, 16 weeks after combined modality treatment. 14 patients died from disease. Eleven patients (68%) experienced regression of their neurological symptoms during or soon after completion of radiotherapy. Seven patients regained their ability to walk, six had pain reduction, three regression of bladder and bowel incontinence. In three patients symptom progression and in two patients no change occurred. Side effects were: myelosuppression (CTC) Grade I: n = 2, Grade II: n = 4, Grade III: n = 4 patients and Grade IV: n = 1. Nine patients had dysphagia, seven mucositis, three suffered from nausea. No late toxicity was observed. Conclusion: Craniospinal radiotherapy is feasible and effective for palliative treatment of leptomeningeal carcinomatosis. As far as the small patient number permits any definite conclusions, combined modality treatment seems superior to irradiation alone.Hintergrund: Eine Leptomeningeosis carcinomatosa, die bei ca. 5% aller soliden Tumoren auftritt, kann die Lebensqualität erheblich beeinträchtigen. Ziel der Studie war es, Machbarkeit und Effektivität einer kraniospinalen Bestrahlung mit und ohne intrathekale Chemotherapie in Bezug auf neurologische Ausfälle und Überleben zu untersuchen. Patienten und Methodik: 16 Patient/innen (medianes Alter 46 Jahre; neun Mammakarzinome, füf Bronchialkarzinome, ein Nierenzellkarzinom, ein unbekannter Primärtumor) mit Meningeosis carcinomatosa, die nach einem medianen Intervall zur Erstdiagnose von 5 Monaten (0–300 Monaten) auftrat, erhielten zwischen Oktover 1995 und Mai 2000 eine Bestrahlung der Neuroachse mit einer medianen Dosis von 36 Gy (à 1,6–2,0 Gy). Zehn Patienten erhielten zusätzlich zwei- bis achtmal eine intrathekale Chemotherapie mit jeweils 15 mg MTX. Resultate: Das mediane Überleben ab Nachweis der Meningeosis betrug 12 Wochen (4–84 Wochen), nach alleiniger Radiatio 8 Wochen, nach kombinierter Therapie 16 Wochen. 14 Patienten verstarben tumorbedingt. Bei elf Patienten (68%) trat während bzw. unmittelbar im Anschluss an die Radiatio ein anhaltender Rückgang der neurologischen Beschwerdesymptomatik ein (siebenmal Wiedererlangung der Gehfähigkeit, sechsmal Schmerzreduktion, dreimal Rückbildung der Blasen- und Mastdarmstörungen). Bei drei Patienten bestand unter Therapie einer Progression der Symptome, in zwei Fällen ein Status idem. Nebenwirkungen waren: Hämatotoxizität (CTC) Grad I: n = 2, Grad II: n = 4, Grad III: n = 4, Grad IV: n = 1. Schluckbeschwerden traten bei neun, eine Mukositis bei sieben und Übelkeit bei drei Patienten auf. Schlussfolgerung: Durch Bestrahlung der Neuroachse ist bei Meningeosis carcinomatosa ein substantieller palliativer Effekt auf die neurologische Symptomatik bei akzeptablen Nebenwirkungen erzielbar. Sofern bei der geringen Fallzahl zu beurteilen, erscheint eine Verlängerung der Überlebenszeit nur durch Kombination mit einer intrathekalen MTX-Chemotherapie erzielbar.

Long-Term Outcome after Combined Radiochemotherapy for Anal Cancer – Retrospective Analysis of Efficacy, Prognostic Factors, and Toxicity

Background: This retrospective study evaluated the efficacy, prognostic factors, and toxicity of combined radiochemotherapy for anal cancer. Patients and Methods: Data of 90 patients treated with radiochemotherapy between 1990 and 2006 were analyzed. Mean follow-up was 30 months (range: 2–129 months). Endpoints were disease-specific survival, local control, freedom from metastasis, and colostomy-free survival. Tumor stage, nodal status, age, sex, tumor site, tumor resection, and radiation dose were analyzed for prognostic value. Acute toxicity was scored according to the RTOG/EORTC scale, late toxicity according to the LENT/ SOMA scale. Results: Disease-specific survival was 86%, local control 79%, freedom from metastasis 92%, and colostomy-free survival 83%. Higher T category was associated with inferior prognosis for colostomy-free survival (p = 0.000), male sex for local control (p = 0.004) and diseasespecific survival (p = 0.002), and tumor site at the anal margin for local control (p = 0.03). 4 of 7 patients with recurrent anal margin tumors had human papillomavirus (HPV)-related disease. 49% of patients suffered from ≧ grade 3 acute toxicity. 3 patients had late toxicity of grade 3 concerning sphincter control. Conclusion: Combined radiochemotherapy for anal cancer is a highly effective therapy with pronounced acute and minor late toxicity. In the case of higher T stage, male sex, and cancer at the anal margin, treatment intensification should be considered.