S. Dinges

HIGH-DOSE RATE INTERSTITIAL WITH EXTERNAL BEAM IRRADIATION FOR LOCALIZED PROSTATE CANCER : RESULTS OF A PROSPECTIVE TRIAL

PURPOSE A prospective phase II trial was carried out to test the feasibility and effectiveness of a combined interstitial with external beam radiotherapy approach for localized prostate cancer. MATERIALS AND METHODS Between October 1992 and December 1994, 82 evaluable patients were treated. T2 and T3 tumours, according to the AJCC classification system of 1992, were found in 21 and 61 cases, respectively. The median follow-up was 24 months; three patients were lost during follow-up. All of the patients were pathologically proven to be node-negative by laparoscopic node dissection of the fossa obturatoria region. A dose of 9 Gy a week was prescribed during the first and second weeks of treatment (10 Gy each week from October 1992 to December 1993) interstitially with high-dose rate Iridium-192 brachytherapy to the prostate and tumour extension beyond the capsule. External beam four-field box irradiation was then given to the prostate to a dose of 45 Gy/25 fractions (40 Gy/20 fractions from October 1992 to December 1993). RESULTS Before starting treatment, a PSA value of > or =10 ng/ml was found in 64.6% (53/82) of patients with a median PSA of 14.0 ng/ml. The median PSA 3, 12 and 24 months after completion of therapy was 1.20, 0.78 and 0.70 ng/ml, respectively. The PSA value was < 1.0 ng/ ml in 52.9% of patients at 2 years. Negative punch biopsies 12 and 24 months after therapy were observed in 69.8% (44/63) and 73. 1% (38/ 52) of patients, respectively. A positive biopsy combined with a PSA value of > 1.0 ng/ml was considered as local failure. The local tumour control rate was 79.5% at 2 years. Acute side-effects were not increased relative to external beam irradiation alone. Severe side-effects were observed in three patients (two of the three patients had additional risk factors (colitis ulcerosa and diabetes mellitus)); they developed rectourethral fistulae requiring colostomy after biopsies from the anterior rectal wall. CONCLUSION The described method is feasible and well tolerable. The three complications observed were not caused by irradiation alone. Biopsies from the anterior rectal wall after definitive high-dose radiotherapy for prostate cancer have to be seen as obsolete. The rate of negative prostate biopsies of 73.1% after 24 months represents an encouraging result.

Local recurrences of soft tissue sarcomas in adults: a restrospective analysis of prognostic factors in 102 cases after surgery and radiation therapy

Between 1974 and 1990, 102 adult patients (age 18-86 years) with the diagnosis of a soft tissue sarcoma (STS) were treated with photons and/or electrons in combination with surgery. The total doses in the initial treatment volume (second order target volume) was 40-50 Gy. For the coning down volume (first order target volume) the median total dose was 59 Gy (range 45-72 Gy). A total of 18% (18/102) local failures was observed. In multivariate analysis, prognostic factors for the occurrence of a local failure were identified as follows: treatment of a primary or recurrent STS (P = 0.02), total dose (P = 0.025) and tumour grade (P = 0.05). Mode of surgery, tumour size (trunk versus extremity), pre- or postoperative radiotherapy, combined chemotherapy and tumour size (T1 versus T2) had no significant impact on the local relapse-free survival. These data give further evidence that combined surgery and radiotherapy is an effective modality in treatment of soft tissue sarcomas.

Combined treatment of inoperable carcinomas of the uterine cervix with radiotherapy and regional hyperthermia

AimThe disappointing results for inoperable, advanced tumors of the uterine cervix after conventional radiotherapy alone necessitates improving of radiation therapy. Simultaneous chemotherapy or altered radiation fractionation, such as accelerated regimen, increase acute toxicity and treatment is often difficult to deliver in the planned manner. The purpose of this phase II study was to investigate the toxicity and effectiveness of a combined approach with radiotherapy and regional hyperthermia.Patients and MethodsFrom January 1994 to October 1995 18 patients with advanced carcinomas of the uterine cervix were treated in combination with radiotherpay and hyperthermia. The patients were treated with 6 to 20 MV photons delivered by a linear accelerator in a 4-field-box technique to a total dose of 50.4 Gy in 28 fractions. In the first and fourth week 2 regional hyperthermia treatments were each applied with the Sigma-60 applicator from a BSD-2000 unit. After this a boost to the primary tumor was given with high-dose-rate iridium-192 brachytherapy by an afterloading technique with 4×5 Gy at point A to a total of 20 Gy and for the involved parametrium anterioposterior-posterioanterior to 9 Gy in 5 fractions.ResultsThe acute toxicity was low and similar to an external radiotherapy alone treatment. No Grade III/IV acute toxicity was found. The median age was 47 years (range 34 to 67 years). In 16 of 18 patients a rapid tumor regression was observed during combined thermo-radiotherapy, which allowed the use of intracavitary high-dose-rate brachytherapy in these cases. Complete and partial remission were observed in 13 and 4 cases, respectively. One paitent die not respond to the treatment. The median follow-up was 24 months (range 17 to 36 months). The local tumor control rate was 48% at 2 years. Median T20, T50 and T90 values were 41.7°C (range 40.3 to 43.2°C), 41.1°C (range 39.2 to 42.5°C) and 39.9°C (range 37.7 to 41.9°C), respectively. Cumulative minutes of T90>40°C (Cum40T90) and cumulative minutes, which were isoeffective to 43°C, were calculated (CEM43T90, CEM43T50, CEM43T20). CEM43T90 was found to be a significant parameter in terms of local tumor control for the 4 hyperthermia treatments (p=0.019).Conclusion sThis treatment modality has proved to be feasible and well tolerable. The rapid tumor shrinkage in the combined approach of radiotherapy with hyperthermia before beginning brachytherapy seems to be a good prerequisite for improving of the disappointing results in cure of advanced cancer of the uterine cervix.ZusammenfassungZielDie unbefriedigenden Ergebnisse lokal fortgeschrittener, inoperabler Tumoren der Cervix uteri nach konventioneller Strahlentherapie machen eine Intensivierung der Therapie erforderlich. Simultane Chemotherapie oder akzelerierte Fraktionierungsschemata erhöhen meist die akute Toxizität, so daß die Therapie in der geplanten Form nur schwer durchgeführt werden kann. Das Ziel dieser Phase-II-Studie wares, Toxizität und Effektivität der kombinierten Strahlentherapie und regionalen Hyperthermie zu untersuchen.Patienten und MethodenVon Januar 1994 bis Oktober 1995 wurden 18 Patientinnen mit lokal fortgeschrittenen Karzinomen der Cervix uteri mit einer kombinierten Strahlentherapie und regionalen Hyperthermie behandelt. Die Patientinnen wurden mit 6-bis 20-MV-Photonen eines Linearbeschleunigers in einer 4-Felder-Box-Technik bis zu einer Gesamtdosis von 50,4 Gy in 28 Fraktionen bestrahlt. Während der ersten und vierten Woche erfolgten jeweils zwei regionale Hyperthermiebehandlungen mit dem Sigma-60-Applikator eines BSD-2000-Gerätes. Nach 50,4 Gy wurde ein Brachytherapie-Boost auf den Primärtumor mit HDR-Iridium 192 in Afterloading technik (4×5 Gy am Punkt A) bis zu einer Dosis von 20 Gy gegeben. Die initial befallenen Parametrien erhielten eine perkutane Dosiserhöhung um 9 Gy in fünf Fraktionen über ventrodorsale Gegenfelder.ErgebnisseDie akute Toxizität war gering, Nebenwirkungen Grad 3 oder 4 wurden nicht beobachtet. Das mediane Alter betrug 47 Jahre (Altersspanne 34 bis 67 Jahre). Bei 16 von 18 Patientinnen wurde eine rasche Tumorregression während der kombinierten Hyperthermie und Strahlentherapie beobachtet, wodurch die intrakavitäre Brachytherapie in diesen Fällen ermöglicht wurde. Eine komplette Remission wurde in 13 Fällen erreicht, viermal eine partielle Remission, in einem Fall erfolgte keine Reaktion. Die mediane Nachbeobachtungszeit betrug 24 Monate (17 bis 36 Monate). Nach zwei Jahren waren 48% der Tumoren lokal kontrolliert. Die medianen T20-, T50-und T90-Werte lagen bei 41,7°C (40,3 bis 43,2°C), 41,1°C (39,2 bis 42,5°C) und 39,9°C (37,7 bis 41,9°C). Zusätzlich wurden die kumulativen Minuten der T90-Werte über 40°C (Cum40T90) und die kumulativen Minuten, die isoeffektiv zu 43°C waren (CEM43T90, CEM43T50, CEM43T20), kalkuliert. Die CEM43T90-Werte für alle vier Hyperthermiebehandlungen waren ein signifikanter prognostischer Parameter in bezug auf die lokale Tumorkontrolle (p=0,019).Schlußfolgerung enDie beschreibene Therapie erwies sich als durchführbar und gut verträglich. Die gute Tumorregression während der kombinierten Therapie bis zum Beginn der Brachytherapie stellt eine günstige Voraussetzung zur Verbesserung der Heilungsergebnisse dieser lokal fortgeschrittenen Tumoren dar.

Chemo-radiotherapy for locally advanced head and neck cancer-long-term results of a phase II trial

The feasibility and effectiveness of a combined chemo-radiotherapy treatment modality for locally advanced head and neck cancer was tested in a phase II trial. Between 1990 and 1993, 74 patients (20 female/54 male) with head and neck cancer stage III (n = 12) and IV (n = 62) were treated with accelerated radiotherapy (72 Gy) and simultaneous chemotherapy (5-FU, folinic acid, mitomycin C). The median follow-up time was 43 months (1-72). Complete remission (CR) was absent in 76% (56/74) of patients and, after subsequent resection of residual lymph nodes, another 8 patients achieved CR. The cumulative local control rate was 72% and disease-specific survival rate was 59% at 4 years. Two patients died with treatment-related conditions (pancytopenia, larynx oedema). By multivariate analysis, only lymph node status was an independent parameter for local control (P = 0.04). This treatment was feasible and toxicity was not a treatment-limiting factor. As a consequence, a German multicentre phase III trial was initiated in 1995.

Virtuelle Simulation@@@Virtual simulation — First clinical results in patients with prostate cancer: Erste klinische Ergebnisse bei Patienten mit Prostatakarzinom

AIM Investigation of options of virtual simulation in patients with localized prostate cancer. PATIENTS AND METHODS Twenty-four patients suffering from prostate cancer were virtual simulated. The clinical target volume was contoured and the planning target volume was defined after CT scan. The isocenter of the planning target volume was determined and marked at patients skin. The precision of patients marking was controlled with conventional simulation after physical radiation treatment planning. RESULTS Mean differences of the patients mark revealed between the 2 simulations in all room axes around 1 mm. The organs at risk were visualized in the digital reconstructed radiographs. CONCLUSIONS The precise patients mark of the isocentre by virtual simulation allows to skip the conventional simulation. The visualisation of organs at risk leeds to an unnecessarily of an application of contrast medium and to a further relieve of the patient. The personal requirement is not higher in virtual simulation than in conventional CT based radiation treatment planning.ZusammenfassungZielUntersuchung von Optionen der virtuellen Simulation bei Patienten mit lokal begrenztem Prostatakarzinom.Patienten und Methode24 Patienten mit einem lokal begrenzten Prostatakarzinom wurden virtuell simuliert. Nach dem Bestrahlungsplanungs-CT erfolgte die Konturierung des Klinischen Zielvolumens und des Planungszielvolumens sowie die Bestimmung des geometrischen Isozentrums, das auf der Haut markiert wurde. Nach Erstellung des Bestrahlungsplanes wurde die Genauigkeit der Markierung des Isozentrums am konventionellen Simulator überprüft.ErgebnisseDie Markierung des Isozentrums an den Patienten erfolgte mit einer mittleren Abweichung von 1 mm in allen drei Ebenen. Auf den digital rekonstruierten Simulationsaufnahmen werden alle vorher konturierten Strukturen wie Zielvolumina und Risikoorgane dargestellt.SchlußfolgerungenAufgrund der Präzision der Markierung des Isozentrums kann bei Einsatz der virtuellen Simulation bei Patienten mit einem lokal begrenzten Prostatakarzinom auf die konventionelle Simulation verzichtet werden. Die Darstellung der Risikoorgane in den digital rekonstruierten Simulationsaufnahmen ermöglicht den Verzicht auf die Kontrastmittelapplikation bei der Simulation und führt zu einer weiteren Entlastung für den Patienten. Der personelle Aufwand ist im Vergleich zur konventionellen CT-gestützten Bestrahlungsplanung nicht höher.AbstractAimInvestigation of options of virtual simulation in patients with localized prostate cancer.Patients and MethodsTwenty-four patients suffering from prostate cancer were virtual simulated. The clinical target volume was contoured and the planning target volume was defined after CT scan. The isocenter of the planning target volume was determined and marked at patient’s skin. The precision of patients marking was controlled with conventional simulation after physical radiation treatment planning.ResultsMean differences of the patient’s mark revealed between the 2 simulations in all room axes around 1 mm. The organs at risk were visualized in the digital reconstructed radiographs.ConclusionThe precise patient’s mark of the isocentre by virtual simulation allows to skip the conventional simulation. The visualisation of organs at risk leeds to an unnecessarity of an application of contrast medium and to a further relieve of the patient. The personal requirement is not higher in virtual simulation than in conventional CT based radiation treatment planning.