Postoperative Strahlentherapie bei Hochrisikopatientinnen mit Mammakarzinom und adjuvanter Chemotherapie

Ohne Zusammenfassung     

Simultane radiochemotherapie mit carboplatin bei patienten mit inoperablen fortgeschrittenen Kopf-Hals-Tumoren der stadien UICCIII und IV

BACKGROUND: The results of treating advanced tumors in the head and neck region with radiotherapy alone are disappointing. Concurrent radiotherapy and chemotherapy may improve this situation. The treatment results of concurrent radiochemotherapy at the University of Rostock were analyzed retrospectively. PATIENTS AND METHODS: From 1991 to 1996 92 patients with head and neck tumors were treated with concurrent radiochemotherapy (1.8 to 63 Gy; 70 mg/m2 carboplatin day 1 to 5 and 29 to 33) with palliative tumor resection (n = 37) or without surgical treatment (n = 55). Remission rate, overall survival and disease-free survival, local control and acute toxicity were analyzed. RESULTS: Six weeks after radiochemotherapy 56.5% of patients had a complete remission, 36% a partial remission and 7.5% "no change". With a median follow-up of 42 months (6 to 74 months) overall survival, disease-free survival and local control were 24.3%, 28.9%, 18.0% 5 years after treatment. All these criteria were significantly better in patients with palliative tumor resection compared to no surgical treatment (uni- and multivariate) and in patients with Stage III than in patients with Stage IV carcinomas (univariate), overall survival was significantly better in patients with Stage III (multivariate). A pretherapeutic Hb level below 7.0 mmol/l (11.27 g/dl) reduced the local control significantly (uni- and multivariate). Grade III and IV mucositis was detected in 10%, Grade III leucopenia in 12% of treated patients. Grade IV leucopenia and Grade III thrombopenia were observed in 1 patient each. CONCLUSION: The toxicity of this treatment is tolerable. However, additional trials must be conducted before considering the palliative tumor resection as standard therapy.     

Kombinierte brusterhaltende Chirurgie, Chemotherapie und Strahlentherapie bei der Behandlung des Mammakarzinoms

Background

The timing of breast conserving surgery, chemotherapy, and radiotherapy in breast cancer treatment has become the subject of increasing interest over the last years.

Patients and Method

Seventy-four patients who underwent postoperative radiotherapy at our institution between 1985 and 1992 form the basis of this study. Median follow-up time was 5 years. Seventy-three percent of patients were pre- or perimenopausal. Almost all patients (91%) were UICC-stage II. Axillary lymph nodes were positive in 95% of cases. Complete gross tumor resection was achieved in all patients, and in 65% final pathological margins were free of invasive or intraductal carcinoma. Postoperatively, 70% of patients received 6 cycles of polychemotherapy (predominantly CMF) before onset of irradiation. The radiation dose was in almost all cases 60 Gy including 10 Gy boost.

Results

Five years after start of treatment overall survival, disease-free survival, and local recurrence rates were 86% (95%-confidence limits, 76 to 93%), 73% (61 to 83%), and 8% (3 to 16%), respectively. For disease-free survival, the only significant prognostic factor was the number of involved lymph nodes: 0 to 3=86%, ≥4=40% (p<0,0001). The interval between surgery and radiation (≤versus >20 weeks) had no significant influence on disease-free survival or local tumor control. In contrast, there was a trend of increased regional and distant failure with shortening of the interval due to the delivery of less than 6 cycles chemotherapy before the onset of radiotherapy.

Conclusions

In our experience, there was no negative impact of a delay of radiotherapy in order to deliver full course chemotherapy before initiation of radiotherapy. However, the low statistical power of this analysis due to the small number of patients must be considered. It appears possible that a less intense chemotherapy before starting radiation treatment correlates with enhanced distant failure and subsequently decreased disease-free survival rates. Therefore, for patients at increased risk for distant metastasis, we prefer to give 6 cycles polychemotherapy before irradiation.     

Hochdosierte Chemotherapie mit autologer Stammzelltransplantation bei Patienten mit rezidivierenden und Hochrisiko-Hirntumoren im Kindesalter

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Intraoperative und perkutane Radiotherapie des Pankreaskarzinoms

Summary Therapeutic strategies in the treatment of pancreatic carcinoma are based on the high number of non-resectable cancers, the high relative radioresistance and the high distant metastases rate. Even in curatively resected carcinomas, a locally effective treatment modality is needed because of the risk of microscopical residual disease in the peripancreatic tissue. The efficacy of radiotherapy is dose dependent. Based on an analysis of published data a dose of more than 50 Gy is recommended, resulting in a high morbidity rate with external beam radiotherapy alone. The use of intraoperative radiotherapy allows locally restricted dose escalation without increased perioperative morbidity. In adjuvant and in primary treatment, local tumor contol was improved (70–90 %). With palliative intent, pain relief was obtained rapidly in over 60 % of patients and led to improved patient performance. As a result of the high distant metastases rate, even in curatively resected carcinomas, the overall prognosis could not be significantly improved. Further dose escalation is limited by the increasing incidence of upper gastrointestinal bleeding (20–30 %). Eingegangen am 19. April 1996 Angenommen am 23. April 1996     

Wertigkeit von Mammographie, Sonographie und MRT zur Verlaufsbeurteilung der neoadjuvanten Chemotherapie bei lokal fortgeschrittenem Mammakarzinom

Purpose

The aim of this study is to give an overview on the surveillance of response to neoadjuvant chemotherapy in locally advanced breast cancer with mammography, ultrasound and breast MRI.

Material and methods

The results of a recently presented study on surveillance in the course of chemotherapy with contrast-enhanced MRI are compared with ratings based on mammography and ultrasound.

Results

Contrast-enhanced MRI correlates best with the histological tumor size when compared with mammography and ultrasound. Tumors with a high HER2 score (2+ with positive FISH test or 3+) show a significantly higher response compared to tumors with a lower HER2 score: size p <0.01, maximum enhancement p <0.01 and area under the curve (AUC) p <0.05. Reduction of tumor size and enhancement are complementary parameters and are not correlated to each other (r=0.22).

Discussion

Contrast-enhanced MRI of the breast is a reliable method for quantification of the response to neoadjuvant chemotherapy. The reductions of tumor size and of tumor enhancement are not correlated. Therefore, it may be reasonable to take both aspects for quantification of therapy response into account. Further studies are needed for evaluation of the value of breast MRI as a prognostic factor.     

Bestrahlung von Schädelbasistumoren mit Kohlenstoffionen bei der GSI Erste klinische Ergebnisse und zukünftige Perspektiven

BACKGROUND: Radiobiological and physical examinations suggest clinical advantages of heavy ion irradiation. We report the results of 23 women and 22 men (median age 48 years) with skull base tumors irradiated with carbon ion beams at the Gesellschaft für Schwerionenforschung (GSI), Darmstadt, from December 1997 until September 1999. PATIENTS AND METHODS: The study included patients with chordomas (17), chondrosarcomas (10) and other skull base tumors (Table 1). It is the first time that the intensity-controlled rasterscan-technique and the application of positron-emission tomography (PET) for quality assurance was used. All patients had computed tomography for three-dimensional-treatment planning (Figure 1). Patients with chordomas and chondrosarcomas underwent fractionated carbon ion irradiation in 20 consecutive days (median total dose 60 GyE). Other histologies were treated with a carbon ion boost of 15 to 18 GyE delivered to the macroscopic tumor after fractionated stereotactic radiotherapy (median total dose 63 GyE). RESULTS: Mean follow-up was 9 months. Irradiation was well tolerated by all patients. Partial tumor remission was seen in 7 patients (15.5%) (Figure 2). One-year local control rate was 94%. One patient (2.2%) deceased. No severe toxicity and no local recurrence within the treated volume were observed. CONCLUSION: Clinical effectiveness and technical feasibility of this therapy modality could clearly be demonstrated in our study. To evaluate the clinical relevance of the different beam modalities studies with larger patient numbers are necessary. To continue our project a new heavy ion accelerator exclusively for clinical use is planned to be constructed in Heidelberg.     

Kombinierte brusterhaltende Chirurgie, Chemotherapie und Strahlentherapie bei der Behandlung des Mammakarzinoms. Der Einflu? des Intervalls zwischen Operation und Bestrahlungsbeginn

Ohne Zusammenfassung The online version of the original article can be found at     

Regression des Yoshida-Sarkoms unter Normoxie und Hypoxie nach fraktionierter Bestrahlung

Purpose

Tumor regression is one of the most important factors determinating the tumor control probability after radiotherapy. The changes in the regression of tumors during fractionated radiotherapy and the application of different radioprotectors or radiosensitizerse make render to assess their effectivity.

Material and Method

The effect of hypoxic breathing (8,1% O₂) on the tumor regression of Yoshida sarcoma was studied using rats of Wistar strain. Different fractionation schedules were used: 10×3 Gy, 6×5 Gy and 3×10 Gy.

Results

No significant changes in the tumor regression after radiotherapy in any group in any time independent from respiratoric hypoxia were recorded. The tumor regression rate was significantly influenced by treatment schedule (p<0.0005).

Conclusions

Our results support the hypothesis of hypoxy-radiotherapy. The acute hypoxic hypoxia, caused due the breathing of hypoxic gas mixture with 8 to 10% oxygen, did not influence the radiation induced tumor regression in animal experiment. For this criterium no protection can be shown. The influence of hypoxy-radiotherapy on the local tumor control is necessary to evaluate in further experiments.     

Dosis-Volumen-Histogramme und 3D-Planung bei der brusterhaltenden Therapie des Mammakarzinoms

Aim

Improvement of the dose homogeneity in radiation treatment of the intact breast using 3D-planning and dose volume histograms.

Patients and Method

3D-planning, including the calculation of dose volume histograms of the planning target volume, was performed on 15 patients, who underwent radiation therapy with tangential photon beams. A standard plan and 2 modified or optimized plans were evaluated. Different dosimetric parameters like maximum dose, mean dose, standard deviation and the fractional volume which receives doses from 95 to 105% of the reference dose were compared and correlated with breast size.

Results

With increasing breast size standard planning leads to increased overdosage, both in magnitude and volume. Individual optimization by modifying weights and wedges gives no improvement in dose homogeneity, whereas a photon energy of 10 MV results in a more homogeneous dose distribution. The drawback of the higher energy is the increased underdosage of the skin.

Conclusion

Using the standard geomertry of tangential fields the dose homogeneity cannot be improved significantly by 3D-planning, compared to our standard technique.     

2D- und 3D-Parameterbilder zur Analyse der Kontrastmittelverteilung bei dynamischen CT- und MR-Untersuchungen

Zusammenfassung Ziel: Bei dynamischen Kontrastmittel- (KM) Studien k?nnen spezifische Merkmale der Zeit/Intensit?ts-Kurve (ZIK) eines jeden Bildpunktes verwendet und in Form von Parameterbildern dargestellt werden. Aufbauend auf bestehenden Konzepten der zweidimensionalen Analyse der KM-Dynamik soll eine dreidimensionale Erweiterung mit ad?quater computergraphischer Visualisierung realisiert werden. Methode: Bildgebung: Intraven?se KM-Injektion; First-pass-Analyse mit CT bei schneller Akquisition einer einzigen Schicht; Untersuchung der l?ngerfristigen KM-Anreicherung mit 40 MR-Schichten (6 Sequenzen alle 90 s=240 Bilder). Softwareentwicklungen: ZIK beliebiger ROIs/VOIs; Parameterbilder: 1. Maximum-Intensit?ts-Projektion (TMIP) aller Pixel als Funktion über die Zeit; 2. zeitliche KM-Gradienten (TG) anhand der ZIK-Amplitude; 3. ZIK-Steigung/Gef?lle; 4. Zeitpunkte der ZIK-Maxima; 5. Korrelationskoeffizienten zu Vergleichs-ZIK. Die berechneten 3D-Daten der KM-Anreicherung wurden mittels multiplanarer Reformatierung, MIP, Oberfl?chenrekonstruktion, Volume Rendering und Textur-Mapping visualisiert und animiert. Ergebnisse: TMIP und TG erlaubten bei First-pass-Analysen die simultane oder getrennte Pr?sentation unterschiedlicher Zeitr?ume des KM-Bolus. Die Korrelationsbilder gestatteten die Hervorhebung von Regionen, die ?hnlichkeiten zu vorgegebenen ZIK-Mustern aufwiesen. Computergraphische Techniken gestatteten 1. ein anatomisch/funktionales Mapping von Originalbild und KM-Anreicherungsverhalten sowie 2. die fusionierte Darstellung von KM-Anreicherungsbetrag und farbkodierter Zeit des KM-Maximums in einem gemeinsamen Bild. Schlu?folgerungen: Die exakte Quantifizierung von Pr?senz, Grad und Ankunftszeit des Kontrastmittels in lokalen Bildregionen unterstützt die Beurteilung der Vaskularisation sowie von isch?mischen bzw. nekrotischen Arealen.      

MR-Perfusions- und spektroskopische Bildgebung bei WHO-Grad-II-Astrozytomen

BACKGROUND: This study evaluates whether MR perfusion imaging and spectroscopic imaging (MRSI) can depict anaplastic areas in WHO grade II astrocytomas, whether these areas are co-localized, and whether the prognosis can be better predicted. MATERIAL AND METHODS: Fifteen patients (nine female, six male, aged 42+/-14 years) with WHO grade II astrocytomas but without preceding radio- or chemotherapy were examined every 3 months with MR perfusion imaging and MRSI (mean follow-up 18 months). Using a region of interest analysis, the regional relative cerebral blood volume (rrCBV) and blood flow (rrCBF) were measured in tumor tissue. In the same areas, choline/creatine (Cho/Cr) and choline/N-acetyl-aspartate (Cho/NAA) ratios were quantified. RESULTS: During follow-up, nine patients had stable disease. In six patients, the tumor showed progression and contrast-enhancement. The progressing tumors had already had higher perfusion (rrCBF 2.1+/-1.4; rrCBV 1.9+/-1.1) parameters than the stable astrocytomas (rrCBF 1.2+/-0.6, p=0.01; rrCBV 1.4+/-0.8, p=0.05) at first examination. However, the Cho/NAA and Cho/Cr ratios only tended to be higher than in stable astrocytomas (Cho/NAA 2.4+/-1.0 vs. 2.0+/-1.5, p=0.23; Cho/Cr 1.7+/-0.6 vs. 1.4+/-0.5, p=0.06). In all six progressing tumors, areas of maximum perfusion and maximum Cho/NAA and Cho/Cr ratio were co-localized. During follow-up, contrast-enhancement was observed in these areas. CONCLUSIONS: MR perfusion imaging can depict anaplastic areas in WHO grade II astrocytomas earlier than conventional MRI and thus enables a better prediction of prognosis.     

Entwicklung und Anwendung dynamischer MRT-Messungen zur Evaluierung von Perfusionsver?nderungen bei Rektumkarzinomen unter Bestrahlung in der klinischen Routine Erste Ergebnisse

Ziel: Entwicklung und Anwendung dynamischer Magnetresonanztomographiemessungen zur Erhebung von Perfusionsparametern bei Rektumkarzinomen unter Bestrahlung in der klinischen Routine. Patienten und Methode: Bei Rektumkarzinompatienten (n = 8), die sich einer präoperativen kombinierten Radiochemotherapie unterzogen, wurden Perfusionsdaten erhoben. An einem 1,5-Tesla-Ganzkörperkernspintomographen wurden ultraschnelle T1-Mapping-Sequenzen zum Erhalt von T1-Maps mit Intervallen von 14 und 120 Sekunden implementiert. Die Meßzeit der dynamischen Messungen betrug 40 Minuten. Die Maßschicht (Schichtdicke 5mm) wurde so gewählt, daß sowohl Tumor als auch arterielle Gefäße dargestellt wurden. Gadolinium-DTPA-(Gd-DTPA-)Konzentrations-Zeit-Kurven wurden nach einem prolongierten Bolus im arteriellen Blut und im Tumor berechnet. Die angewendete Methode erlaubte eine räumliche Auflösung von 2 2 2 2 5 mm und eine zeitliche Auflösung von 14 Sekunden. Die Meßdaten wurden vor und in konstanten Intervallen während Therapie erhoben. Ergebnisse: Die räumliche und zeitliche Auflösung der T1-Maps war ausreichend, um Areale mit unterschiedlicher Kontrastmittelkinetik innerhalb des Tumors zu erfassen sowie die großen Beckenarterien sicher zu identifizieren. Bei sechs Patienten konnten Gd-DTPA-Konzentrationskurven im Tumor unter Therapie erhoben werden. Der Perfusionsindex (Pi) versus Strahlendosis zeigte eine signifikante Zunahme in der ersten oder zweiten Woche der Bestrahlung, bevor er entweder kontinuierlich absank oder nach anfänglichem Abfall einen erneuten Anstieg aufwies. Der durchschnittliche Pi-Ausgangswert betrug 0,16 (ǂ,049), das durchschnittliche Pi-Maximum war 0,23 (- 0,058). Die relativen Perfusionsveränderungen betrugen zwischen 20 und 83%. Schlußfolgerung: Unsere Ergebnisse zeigen, daß sich die verwendete Methode zur Erfassung von Perfusionsparametern unter Bestrahlung eignet und in der klinischen Routine anwendbar ist. In der Zukunft könnte mittels der gewonnenen Daten eine individualisierte tumor- und perfusionsangepaßte Therapieoptimierung bei kombinierter Radiochemotherapie durchgeführt werden. Purpose: This study was aimed at measuring microcirculatory parameters and contrast medium accumulation within the rectal carcinoma during fractionated radiotherapy in the clinical setting. Materials and Methods: Perfusion data were observed in patients with rectal carcinoma (n = 8) who underwent a properative combined chemo/radiotherapy. To acquire perfusion data, an ultrafast T1 mapping sequence was carried out on a 1.5-Tesla whole body imager to obtain T1 maps at intervals of 14 or 120 seconds. The overall measurement time was 40 minutes. The transaxial slice thickness (5mm) was chosen in such a way that both arterial vessels and the tumor could be clearly identified. The gadolinium-DTPA (Gd-DTPA) concentration time curve was evaluated for arterial blood and tumor after intravenous constant rate infusion. The method allows a spatial resolution of 2 2 2 2 5 mm and a temporal resolution of 14 seconds. Patients underwent MR imaging before and at constant intervals during fractionated radiotherapy. Results: Spatial and temporal resolution of dynamic T1 mapping was sufficient to reveal varying CM accumulation levels within the tumor and to identify the great arteries in the pelvis. In 6 patients Gd-DTPA concentration-time-curves were evaluated within the tumor during radiation. Pi index of Gd-DTPA versus radiation dose showed a significant increase in the first or second week of treatment, then either returned slowly to pretreatment level or a renewed increase was observed. The average Pi-value at the beginning was 0.16 (ǂ.049), reaching highest level of 0.23 (ǂ.058). In all groups the rise from the Pi-value to the Pi-maximum was statistically significant. The relative increase in perfusion ranged between 20 to 83%. Conclusion: The results show, that the ultrafast MR-technique described above provide a suitable tool for monitoring tumor microcirculation during therapeutic interventions and offers the potential for an individualized optimization of therapeutic procedures.     

Blutalkoholmaximum und Resorptionszeit bei ganz kleinen Alkoholdosen

Ohne Zusammenfassung