Heinz D. Böttcher

Prophylactic endovascular radiotherapy to prevent intimal hyperplasia after stent implantation in femoropopliteal arteries

AbstractPurpose: Recurrent stenosis or occlusion by intimal hyperplasia occurs in up to 40% of patients with tantalum stent implantations in femoropopliteal arteries and greatly restricts their usefulness. We evaluated the effect of prophylactic endovascular radiotherapy on stenosed/occluded\ stents. Methods: We investigated prophylactic endovascular radiotherapy with a surface dose of 12 Gy using an iridium 192 source as a means to reduce or eliminate recurrent stenosis in 4 patients with stenosed/occluded stents, 6–8 months after the original implantation. Confirmatory diagnostic atherectomy, PTA or laser recanalization and endovascular radiotherapy were performed. Results: None of the four has developed recurrent obstruction within 23 to 30 months after this treatment, which up to now shows no short-term or long-term complications. Conclusion: We conclude that this limited experience is promising enough to warrant further study.

192Ir endovascular brachytherapy for avoidance of intimal hyperplasia after percutaneous transluminal angioplasty and stent implantation in peripheral vessels: 6 years of experience

PURPOSE Percutaneous transluminal angioplasty (PTA) with or without stent implantation is the accepted standard in the therapy of occlusive arterial disease. Despite improvements in the technique and medical equipment, there is still a restenosis rate of up to 40%. A high-dose-rate afterloading technique to avoid vascular stenosis or occlusion after PTA and subsequent stent implantation caused by intimal hyperplasia is presented with long-term results. METHODS AND MATERIALS Intravascular brachytherapy with a 10-Ci 192Ir source was performed in cases of recurrent vascular occlusion or stenosis which appeared within 6 months after a previous PTA. After recanalization by PTA and stent implantation, a 9-Fr ReKa catheter was positioned within the stent to center the applicator with its tip 2 cm below the stent. This catheter served as a guide for a 5-Fr flexible applicator. After this procedure the isodose was calculated and a 12-Gy to 3-mm source distance was applied. The procedure was followed by 72 h of heparinization. RESULTS From May 1990 to June 1996, 28 patients (21 male and seven female) were treated with endovascular brachytherapy. All patients had a clinically relevant restenosis or reocclusion of the arteria femoralis. Follow-up time ranged from 1 to 71 months. Twenty-eight patients had a sufficient follow-up time; 25 of these patients were examined. Twenty-one patients had treated vessel segments; four patients had no flow in the treated area. Two patients moved away with unknown addresses, and one patient died without any follow-up examination. Radiation-associated side effects were not notable. CONCLUSION Intraluminal brachytherapy with 192Ir is a safe and useful procedure to avoid endovascular hyperplasia after transluminal percutaneous angioplasty.

Prophylaxis with povidone-iodine against induction of oral mucositis by radiochemotherapy.

Oral mucositis is a frequent complication of radiochemotherapy. The origin of radiation-induced mucosal lesions is iatrogenic in nature, although further development of mucositis is essentially influenced by infection. It can be assumed that disinfection measures should decrease the severity of mucositis induced by radiochemotherapy. Therefore, in a prospective randomised study the efficacy of prophylactic oral rinsing with a disinfection agent was investigated. A randomised, prospective comparative trial was conducted with 40 patients undergoing radiochemotherapy of the head and neck region because of malignant disease. The treatment scheme consisted of irradiation to the tumour region and adjacent lymph nodes, with a total dose of 71.3 Gy, and simultaneous chemotherapy with carboplatin (60 mg/m2) on days 1–5 and 29–34. In all patients mucositis prophylaxis with nystatin, rutosides, panthenol and immunoglobulin was undertaken. In addition, 20 patients rinsed the oral cavity 4 times daily with povidone-iodine solution, while the group for comparison rinsed with sterile water. Clinical examination of the oral mucosa was performed weekly. Onset, grading and duration of mucositis were used as the main variables. Clinically manifest oral mucositis was observed in 14 patients in the iodine group (mean grading: 1.0) and in all 20 patients in the control group (mean grading: 3.0). The total duration (mean) of clinically observed mucositis was 2.75 weeks in treatment patients and 9.25 weeks in control patients. Median AUC (area under curve for grade vs duration) was 2.5 in the iodine rinsing patients and 15.75 in control patients. All differences found between the two groups were statistically significant. Increased iodine incorporation was not observed. A pathologic rise in thyroid hormone levels was not found in the iodine group. The results obtained indicate that incidence, severity and duration of radiochemotherapy-induced mucositis can be significantly reduced by oral rinsing with povidone-iodine in addition to the standard prophylaxis scheme. It can be concluded that rinsing with povidone-iodine is an easy, cheap and safe prophylactic method and can be recommended as a supportive treatment during antineoplastic treatment of the head and neck region.

High precision film dosimetry with GAFCHROMIC films for quality assurance especially when using small fields.

Treatment units for radiosurgery, brachytherapy, implementation of seeds, and IMRT generate small high dose regions together with steep dose gradients of up to 30%-50% per mm. Such devices are used to treat small complex-shaped lesions, often located close to critical structures, by superimposing several single high dose regions. In order to test and verify these treatment techniques, to perform quality assurance tasks and to simulate treatment conditions as well as to collect input data for treatment planning, a GAFCHROMIC film based dosimetry system for measuring two-dimensional (2-D) and three-dimensional (3-D) dose distributions was developed. The nearly tissue-equivalent radiochromic GAFCHROMIC film was used to measure dose distributions. A drum scanner was investigated and modified. The spectral emission of the light source and the filters together with the efficiency of the CCD filters for the red color were matched and balanced with the absorption spectra of the film. Models based on refined studies have been developed to characterize theoretically the physics of film exposure and to calibrate the film. Mathematical descriptions are given to calculate optical densities from spectral data. The effect of darkening has been investigated and is described with a mathematical model. The influence of the scan temperature has been observed and described. In order to cope with the problem of individual film inhomogeneities, a double irradiation technique is introduced and implemented that yields dose accuracies as good as 2%-3%. Special software routines have been implemented for evaluating and handling the film data.

Stellenwert der18F-Fluordeoxyglucose-Positronen-emissionstomographie in der Radiotherapieplanung von Kopf-Hals-Tumoren

ZusammenfassungHintergrundEine exakte Ausbreitungsdiagnostik ist Voraussetzung für die individualisierte Bestrahlungsplanung bei Patienten mit Kopf-Hals-Tumoren. Trotz hoher Zuverlässigkeit der in der Routine eingesetzten Verfahren Computer-und Kernspintomographie ist die sichere Diagnostik eines lymphonodalen Tumorbefalls oft nicht möglich. Wir untersuchten im Rahmen einer Studie, ob die zusätzliche Durchführung einer18F-Fluordeoxyglucose-Positronenemissionstomographie (FDG-PET) hier einen für die Radiotherapieplanung relevanten Informationsgewinn erbringt.Patienten und MethodeUntersucht wurden Daten von 34 Patienten mit Plattenepitheltumoren der HNO-Region, bei denen im Rahmen des Staging vor Radiotherapieplanung zusätzlich zu Sonographie, MRT, CT und Panendoskopie eine FDG-PET durchgeführt wurde. Ausgewertet wurde, wie häufig und in welchem Ausmaß das Ergebnis der PET eine Änderung des geplanten Bestrahlungsfeldes bzw. des Behandlungskonzeptes erforderte.ErgebnisseBei 7/12 der Rezidive und 9/22 der Primärtumoren wurde durch die FDG-PET ein konventionell nicht festgestellter Tumorbefall diagnostiziert. In allen Fällen war eine Änderung des Therapiekonzeptes oder des Bestrahlungsvolumens erforderlich. Überdurchschnittlich häufig waren therapierelevante PET-Befunde bei Rezidivtumoren, großen Primärtumoren (T3 und T4) und bei Primärtumoren mit ausgedehntem Lymphknotenbefall (N2 und N3).SchlußfolgerungBesonders bei Rezidivtumoren und fortgeschrittenen Kopf-Hals-Tumoren erbringt die FDG-PET einen Gewinn an diagnostischer Information für die Radiotherapieplanung. Bei dieser Patientengruppe sowie bei unklarer Befundlage sollte die FDG-PET als zusätzliches diagnostisches Verfahren im prätherapeutischen Staging vor der Entscheidung über Therapiestrategie und Bestrahlungsplanung hinzugezogen werden.AbstractPurposeAn individualized radiation treatment planning in patients with head and neck tumors requires an exact definition of tumorspread. Despite of high reliability of methods like computed tomography, sonography or magnetic resonance imaging used in daily routine, the correct diagnosis of lymphonodal tumor infiltration is often not possible. In a prospective trial, we examined whether an additional FDG-PET gives a relevant gain of information for radiation treatment planning.Patients and MethodsWe studied data of 34 patients with histologically confirmed squamous cell carcinoma of the head and neck who received a FDG-PET prior to treatment planning additionally to conventional staging procedures. The extent of changes of treatment strategy or target volume due to additional FDG-PET finding were analyzed.ResultsIn 9/22 of patients with primary tumors and in 7/12 of patients with recurrent disease, FDG-PET detected additional tumor manifestations. In all cases, changes of treatment strategy or target volume were necessary. Regarding patients with primary tumors, the percentage of treatment modifications was highest in patients with large tumors (T3 and T4) and patients with advanced lymph node involvement (N2 and N3).ConclusionsEspecially in patients with recurrent disease and patients with advanced tumor stages, FDG-PET is able to give clinically relevant information compared to conventional staging procedures. Therefore, in these group of patients a FDG-PET study prior to radiotherapy planning should be considered.PURPOSE An individualized radiation treatment planning in patients with head and neck tumors requires an exact definition of tumorspread. Despite of high reliability of methods like computed tomography, sonography or magnetic resonance imaging used in daily routine, the correct diagnosis of lymphonodal tumor infiltration is often not possible. In a prospective trial, we examined whether an additional FDG-PET gives a relevant gain of information for radiation treatment planning. PATIENTS AND METHODS We studied data of 34 patients with histologically confirmed squamous cell carcinoma of the head and neck who received a FDG-PET prior to treatment planning additionally to conventional staging procedures. The extent of changes of treatment strategy or target volume due to additional FDG-PET findings were analyzed. RESULTS In 9/22 of patients with primary tumors and in 7/12 of patients with recurrent disease, FDG-PET detected additional tumor manifestations. In all cases, changes of treatment strategy or target volume were necessary. Regarding patients with primary tumors, the percentage of treatment modifications was highest in patients with large tumors (T3 and T4) and patients with advanced lymph node involvement (N2 and N3). CONCLUSIONS Especially in patients with recurrent disease and patients with advanced tumor stages, FDG-PET is able to give clinically relevant information compared to conventional staging procedures. Therefore, in these group of patients a FDG-PET study prior to radiotherapy planning should be considered.

Multimodality Treatment Including Postoperative Radiation and Concurrent Chemotherapy with Weekly Docetaxel is Feasible and Effective in Patients with Oral and Oropharyngeal Cancer

Background:To examine the feasibility and efficacy of weekly docetaxel with concurrent radiation as postoperative treatment in a multimodality approach to oral and oropharyngeal cancer.Patients and Methods:94 patients (Table 1) with primary resectable squamous cell carcinoma of the oral cavity and oropharynx (UICC stage I 14%, II 15%, III 18%, IV 53%; Table 2) were treated with a multimodality therapy program consisting of neoadjuvant intra-arterial high-dose chemotherapy (cisplatin 150 mg/m2 with parallel systemic sodium thiosulfate 9 g/m2 for neutralization), followed by surgery of the primary and neck, and postoperative concurrent radiation and chemotherapy with weekly docetaxel (20–30 mg/m2; Table 3). Chronic toxicities were followed over a period of 5 years.Results:At a median follow-up of 4 years, the 5-year survival rate for all 94 patients was 80%, and disease-free survival was 73% (Figures 1 and 2). Among patients with advanced disease (stage III and IV), survival was 83 and 59%, respectively (Figure 4). Grade 3 and 4 mucositis was the main acute toxicity necessitating supportive care. Long-term toxicity appears to be moderate (Table 4). The maximum tolerated dose of weekly docetaxel was 25 mg/m2.Conclusions:Concurrent radiation and chemotherapy with weekly docetaxel is a feasible postoperative treatment in a multimodality approach to oral and oropharyngeal cancer, resulting in high overall and disease-free survival. This approach warrants further evaluation in prospective randomized trials.Hintergrund:Untersuchung der Durchführbarkeit und Effektivität einer wöchentlichen Docetaxelapplikation bei konkomitanter Bestrahlung in einem multimodalen Behandlungskonzept von Mundhöhlen- und Oropharynxkarzinomen.Patienten und Methoden:94 Patienten (Tabelle 1) mit primären resektablen Plattenepithelkarzinomen der Mundhöhle und des Oropharynx (UICC-Stadium I 14%, II 15%, III 18%, IV 53%; Tabelle 2) wurden mit einem multimodalen Therapiekonzept behandelt, das aus einer neoadjuvanten intraarteriellen Hochdosischemotherapie (150 mg/m2 Cisplatin mit paralleler systemischer Neutralisierung durch 9 g/m2 Natriumthiosulfat), einer Radikaloperation des Primarius und des Halses sowie einer postoperativen konkomitanten Bestrahlung und Chemotherapie mit wöchentlicher Docetaxelgabe (20–30 mg/m2) bestand (Tabelle 3). Chronische Nebenwirkungen wurden über 5 Jahre hinweg beobachtet.Ergebnisse:Nach einem medianen Follow-up von 4 Jahren lag die 5-Jahres-Überlebensrate aller 94 Patienten bei 80% und das krankheitsfreie Überleben bei 73% (Abbildungen 1 und 2). Bei Patienten mit fortgeschrittener Erkrankung (Stadium III und IV) lag das Überleben bei jeweils 83% und 59% (Abbildung 4). Eine Mukositis der Grade III und IV war die hauptsächliche Akuttoxizität, die eine supportive Therapie nötig machte. Die Langzeittoxizität schien moderat zu sein (Tabelle 4). Die maximal tolerierte wöchentliche Docetaxeldosis war 25 mg/m2.Schlussfolgerungen:Die konkomitante Bestrahlung und Chemotherapie mit wöchentlicher Docetaxelgabe ist eine durchführbare postoperative Behandlung in einem multimodalen Therapiekonzept für Mundhöhlen- und Oropharynxkarzinome, die in einem hohen Gesamt- und krankheitsfreien Überleben resultiert. Dieser Therapieansatz erfordert eine weitere Bewertung in prospektiven randomisierten Studien.

Survival of very young children with medulloblastoma (primitive neuroectodermal tumor of the posterior fossa) treated with craniospinal irradiation

PURPOSE Very young children with medulloblastoma are considered to have a worse prognosis than older children. As radiotherapy remains an important part of the treatment, the adverse prognosis could be due to inadequate radiation treatment rather than biological factors. We analyzed the published literature to examine the impact of radiotherapy on survival in this group. METHODS AND MATERIALS A Medline search was performed and we reviewed studies of treatment of medulloblastoma where radiotherapy was delivered using megavoltage equipment and the minimum follow-up allowed the calculation of 5-year survival rates. RESULTS Thirty-nine studies were published between 1979 and 1996 with a treatment including craniospinal irradiation and boost to the posterior fossa. Eleven studies comprising 1366 patients analyzed survival by age at diagnosis. Eight of 11 studies showed a worse 5-year survival for the younger patient group which reached statistical significance in two. There is also a suggestion of a higher proportion of children with metastatic disease at presentation in the very young age group. The usual policy in younger children was to give a lower dose of radiotherapy to the craniospinal axis (CSA) and posterior fossa (PF) with reduction of dose in the range of 15 to 25% compared to standard treatment. As dose reduction to the posterior fossa is associated with worse survival and local recurrence is the predominant site of failure, the major determinant of worse survival in very young children with medulloblastoma may be suboptimal radiotherapy. Protocols including postoperative chemotherapy with delayed, omitted, or only local tumor irradiation do not reach survival rates of protocols with standard radiotherapy, also suggesting a continued importance for irradiation. CONCLUSION Very young children with medulloblastoma have a worse prognosis than older children. Inadequate radiation dose and technique to the primary tumor region may be a major contributing factor. Current chemotherapeutic regimes alone are not sufficient to compensate for reduced radiation doses and volumes.

Bilateral breast carcinoma versus unilateral disease. Review of 498 patients.

In literature data, an uncertainty exists whether occurrence of bilateral breast cancer decreases the survival probability of affected patients. Therefore, we analyzed the medical records of 498 postoperatively irradiated (1977-1982) female breast cancer patients (T1-4,N0-3,M0). In the follow-up time, in 36 patients a bilateral breast carcinoma treated by surgery with or without radiotherapy was found. The 10-year overall survival rates were 54% in patients who had unilateral disease, compared with 56% in bilateral carcinoma patients, respectively. The incidence of metastasis did not differ between both groups: 24.2% versus 38.8%. Eleven percent of unilateral cancers recurred; in the other group, local failure of the first and second tumor was observed in 19.4% and 11.1%, respectively. We conclude that the occurrence of bilateral breast cancer has no significant impact on survival, although the development of local failures and metastases seems to be more frequent. The therapeutic strategy in bilateral carcinoma should resemble the treatment procedure in unilaterally affected patients.

Can prophylactic application of immunoglobulin decrease radiotherapy-induced oral mucositis?

Therapeutic application of immunoglobulin is reported to be successful in radiation-induced oral and oropharyngeal mucositis. In this study the efficacy of prophylactic application of immunoglobulin was investigated. In 42 patients with head and neck cancer, postoperative radiation treatment or radiation combined with chemotherapy was performed. In 20 consecutive patients, prophylactic mucositis treatment consisted of panthenol (4 x 10 ml/day) and nystatin (4 x 1 ml/day). The 22 following patients received, supplementary to panthenol and nystatin, 800 mg (5 ml) human immunoglobulin intramuscularly once weekly. During the treatment time, the degree of mucositis was examined 3 times a week. The distribution of maximal mucositis degree revealed slightly more severe mucous membrane reaction in the control group compared with the immunoglobulin group (n.s.). The analysis of mean mucositis degrees in both groups demonstrated statistically significant differences (t test, p = 0.031) related to the entire group (n = 42) and to those 16 patients receiving radiation combined with chemotherapy. There was no significant immunoglobulin-induced effect on mucositis in patients treated by radiation alone. The time from the beginning of therapy to the first interruption could be prolonged 5 days in the immunoglobulin group (n.s.). In conclusion, it is demonstrated that the prophylactic application of immunoglobulin seems to lower the degree of radiation-induced mucositis. In comparison to the published data about therapeutically given immunoglobulin, the clinical efficacy of the prophylactic application of immunoglobulin as it is performed in this study is less evident.

Influence of irradiation on therapy-associated psychological distress in breast carcinoma patients

PURPOSE To confirm our assumptions regarding factors that apparently cause psychological distress related to adjuvant radiotherapy in breast cancer patients and to evaluate variables that can predict therapy-associated distress. METHODS AND MATERIALS Between January 1997 and April 1998, 111 women (33-84 years) with early-stage breast cancer were irradiated (56 Gy) after breast-conserving surgery. Patients were given self-assessment questionnaires on the first and last day of radiotherapy. Statistical analysis was performed using the structural equation model LISREL, variance analysis, and regression analysis. RESULTS The internal subject-related factors (coping, radiation-related anxiety, physical distress, psychological distress) reciprocally influenced each other, whereas external radiotherapy-specific factors (environmental influence, confidence in the medical staff) were causally related to coping, anxiety, and distress. Fifty-three percent of the women felt distressed because cancer affected the breast; 48% were initially afraid of radiotherapy. For 36%, anxiety was not reduced during treatment. Highly distressed women were identified by the following parameters: < or =58 years; initial anxiety; they were affected by having breast cancer, were negatively affected by environmental factors, and did not find distraction helpful. CONCLUSION Despite considerable individual variability in breast cancer patients, it seems possible to identify women who run a high risk of therapy-associated distress. In these patients, psychosocial support is necessary to reduce treatment-related anxiety and to stabilize confidence in the medical staff.