[Postoperative radiotherapy of the chest wall in patients with male breast cancer]. / Postoperative Strahlentherapie der Thoraxwand beim Mammakarzinom des Mannes.

INTRODUCTION: We analysed our long-term results with postoperative radiotherapy of the chest wall in male breast cancer patients with respect to local control and survival. METHODS: Twenty-five patients with 26 histological proven carcinomas of the male breast underwent postoperative radiotherapy of the chest wall with (n = 15) or without regional lymphatics after mastectomy. Additionally 13 patients received adjuvant hormones and 3 patients adjuvant chemotherapy. Median age at treatment was 62.2 years (45.9-78.5 years). Median follow-up was 15.3 years (7.7-27.5 years). RESULTS: Overall survival after radiotherapy was 28 %, disease-specific survival was 64 %. Actuarial 3-, 5- and 10-year survival was 72 %, 56 % and 35 %. Median survival time was 6.1 years. Actuarial progression-free survival was 80 %, 52 % and 43 % after 3, 5 and 10 years, respectively. Local tumor control was 92 % (24 / 26). Survival was significantly affected by the presence of lymph node metastases (p < 0.01) and localisation of the tumor in the right breast (p < 0.04). CONCLUSION: Postoperative radiotherapy is an important part of the management of male breast cancer to improve local control and progression-free survival. The presence of lymph node metastases significantly impairs survival.

[The effect of haemoglobin levels on prognosis and quality of life of patients with bronchial carcinoma]. / Einfluss des Hämoglobinwertes auf Prognose und Lebensqualität beim Bronchialkarzinom.

As a consequence of tumour and therapy related effects anaemia is a particularly frequent occurrence in patients with lung cancer. The ensuing symptoms such as dyspnoea, fatigue and decreased general health reduce their quality of life and can impede if not altogether prevent an effective cytostatic therapy. A positive outcome after oxygen-dependent anti-tumour therapy, for example radiation therapy or various cytostatic treatments as well, can be reduced or even put at risk when tumour tissue is hypoxic. In order to treat anaemia, recombinant human erythropoietin can be used beside blood transfusions. Erythropoietins are well tolerated and allow for a long-lasting, gradual increase of Hb-levels, which cannot be achieved via transfusions. Furthermore, transfusion risks such as intolerance reactions or disease transmission can also be avoided. The various studies presented here evaluated the impact of anaemia treatment with erythropoietins on the need for transfusions and quality of life of patients with lung cancer over the last few years. They all agreed in their conclusion that both parameters can be improved with erythropoietin therapy. It turned out that the patients' quality of life improved most when Hb levels reached around 12 g/dl . Studies examining the impact of anaemia treatment on a patient's prognosis also showed positive effects in the majority of cases. In order to investigate this issue, our Heidelberg work group has designed a prospective, randomised phase-III study on NSCLC patients, which will be explained in detail further down.

Plasmocytoma of the urethra.

CASE HISTORY AND FINDINGS: A 35-year-old male patient presented with a 1-year history of hesitancy in voiding. An urethrogram revealed urethral stricture, therefore an urethrotomy with biopsies was performed. Histologic results suggested the diagnosis of extramedullary mature plasmocytoma. TREATMENT AND OUTCOME: After external beam radiotherapy with a total dose of 45 Gy the patient is disease-free without any therapy-related late effects after a follow-up of 36 months. CONCLUSION: Primary localization of extramedullar plasmocytomas in the genitourinary tract is very rare. This case report discusses a case of a male patient suffering from plasmocytoma of the urethra, who could be treated successfully by primary external beam radiotherapy.

[Reirradiation of chest wall local recurrences from breast cancer]. / Rebestrahlung der Thoraxwand bei lokal rezidivierenden Mammakarzinomen.

OBJECTIVE: The aim of this article was to describe the radio-therapeutic treatment options in previously irradiated patients suffering from breast cancer local recurrences and to review the literature. MATERIAL AND METHODS: Reirradiation of the chest wall can be performed using electron beams or alternatively CLDR/PDR (continuous/pulsed low dose rate) brachytherapy techniques with large skin moulds. With both techniques high doses can be applied to the chest wall while deeper-seated organs (lung, heart) can be spared to a large extent. Electron-beam therapy is readily available and the depth of treatment can be easily controlled by selecting the appropriate energy. The protracted irradiation schedule of CLDR/PDR brachytherapy results due to radiobiological reasons in a broad therapeutic ratio and safe treatment time. RESULTS: In the literature, more than 250 cases being reirradiated for chest wall local recurrences have been published. After retreatment using electron beams complete remissions were obtained in 41-74 % of the patients (brachytherapy 79-82 %). Severe grade IV complications (RTOG/EORTC) occurred in less than 10 % of the patients. CONCLUSIONS: With regard to the limited treatment options reirradiation of chest wall local recurrences resulted in high local control rates while toxicity remained acceptable. These data weaken the radio-therapeutic dogma that reirradiation of the chest wall may not be possible.

[Intraoperative extracorporeal irradiation and replantation in local treatment of primary malignant bone tumors]. / Intraoperative extrakorporale Irradiation und Replantation (IEIR) in der lokalen Behandlung primär maligner Knochentumoren.

In 13 patients with primary malignant bone tumors (10 Ewing's sarcoma, 1 parosteal osteosarcoma, 1 adamantinoma recurrence, and 1 MFH) local therapy was performed as intraoperative extracorporeal irradiation and replantation (IEIR) of the involved bone segment (5 tibia, 2 femur, and 6 pelvis). Of the 13 patients (69%), 9 are alive at the time of the follow-up (5 CDF, 4 AWM(treated)) and 4 patients died of disease (DOD). Up to now during the follow-up of 32 months (6-57), no local recurrence was observed in the replanted bone segments. The complication rate was very high (18 complications in 11 of the 13 patients, including 6 cases with complication V degrees according to Ruggieri with loss of the reconstruction). The typical complication is severe local infection necessitating removal of the replant. In cases of mechanical failure, the replanted segment could mostly be preserved by surgical revision and autologous bone grafting. If serious complications can be managed or avoided, functional results can be achieved. IEIR must be seen as an extraordinary reconstruction procedure in cases where established procedures such as endoprosthesis, biological reconstructions, or rotationplasties cannot be used or are refused by the patient.

Treatment planning intercomparison for spinal chordomas using intensity-modulated photon radiation therapy (IMRT) and carbon ions.

Spinal chordomas cannot be treated with an effective dose using conventional radiation therapy (RT) without exceeding the tolerance dose of the spinal cord while ensuring sufficient target coverage at the same time. In this study we investigate the potential physical advantages of combined photon intensity-modulated radiation therapy (IMRT) and raster-scanned carbon ion RT over photon IMRT alone. For a representative patient we generated a carbon ion RT plan and a photon IMRT plan. Additionally, combined plans consisting of both carbon ions and photon IMRT were calculated using ratios of 20:40 GyE, 30:30 GyE and 40:20 GyE. The best target coverage was obtained using carbon ions alone. Using a combination of photon IMRT and carbon ions, the target coverage was better than with photon IMRT alone. Due to the applied dose constraints, the sparing of the spinal cord was comparable for all plans. Using carbon ions alone, the non-target tissue volume irradiated to at least 30 GyE/50.4 GyE was reduced by 72%/84% compared to photon IMRT alone. These advantages were evident even with combined techniques. The actually delivered dose distribution is expected to be more dependent on patient misalignment with carbon ions compared with photon IMRT. A combination of carbon ions and photon IMRT might be preferable in order to profit by the physical advantages of carbon ions while ensuring a safe treatment.

Data security and protection in cross-institutional electronic patient records.

This paper aims at identifying the specific legal requirements concerning data security and data protection of patient health data that apply to a cross-institutional electronic patient record (EPR) and describes possible solutions for meeting these requirements. In Germany, the legal framework for such records provide that disclosure of patient health information to physicians of third-party institutions is only allowed in case that it is necessary for the joint treatment of the patient, i.e. in case of a "treatment connection". As a first step, the functionality of a remote-access architecture was proven allowing a one-way connection between the EPR systems of two health institutions in Germany, which jointly treat tumor patients. Besides, a signature system model for ensuring the integrity and authenticity of medical documents was developed and implemented in the existing information system architecture of the University Medical Center of Heidelberg. Especially in Germany, the legal framework for cross-institutional EPRs is very complex and has a considerable influence on the development and implementation of cross-institutional EPRs. However, its introduction is thought to be valuable, since a cross-institutional EPR will improve communication within shared care processes, and thus improve the quality of patient care.

[Modern techniques in the radiotherapy of prostate cancer. Non-surgical treatment options for localized stages]. / Moderne Techniken in der Radiotherapie des Prostatakarzinoms. Nichtoperative Optionen bei lokalisierten Stadien.

The implementation of computer-assisted three-dimensional radiotherapy treatment planning methods based on computed tomography together with sophisticated beam modeling with individual blocks and multi-leaf-collimators in the 90's enabled the creation of steep dose gradients between the target volume and surrounding radiosensitive normal tissue. For prostate cancer, a clear dose dependence between the treated radiation dose and the treatment success is proven, especially for patients with intermediate and unfavorable prognostic criteria. However, with conventional radiotherapy, rectum and urinary bladder are limiting the applicable dose. New technical methods allow a safe dose escalation without increasing of treatment-related toxicity. An improvement in terms of PSA remission and local control was yielded. This article presents the different established external beam and interstitial treatment techniques and their clinical results.

Intensity modulated radiotherapy (IMRT) for recurrent, residual, or untreated skull-base meningiomas: preliminary clinical experience.

OBJECTIVE: To investigate the feasibility of using intensity modulated radiotherapy (IMRT) for complex-shaped benign meningiomas of the skull base and report clinical experience. METHODS: Twenty patients with benign skull-base meningiomas WHO degrees I (histopathologically proven in 16/20) were treated with IMRT between June 1998 and August 1999. Each tumor was complex in shape and adherent to, or encompassed, organs at risk (cranial nerves, optic apparatus, and brainstem). All patients, immobilized in a customized head mask integrated into a stereotactic system, were planned on an inverse treatment planning system using 5 or 7 coplanar, equidistant beams and 5 intensity steps. Each treatment plan was verified extensively before treatment. Follow-up with MRI and clinical examination was performed at 6 and 18 weeks and every 6 months thereafter. RESULTS: Target volumes ranged from 27 to 278 cc (median: 108 cc). Mean dose in 32 fractions ranged between 55.8 and 58.2 Gy. At median follow-up of 36 months (range: 31-43 months), pre-existing neurologic symptoms improved in 12/20 (60%), remained stable in 7/20 (35%), and worsened in 1 (5%) patient. Radiographic follow-up revealed significant tumor shrinkage 6 weeks post-IMRT in 2 patients and partial remission in 3 more patients at 9-17 months; other tumor volumes remained stable. There was no radiation-induced peritumoral edema, increase in tumor size, or new onset of neurologic deficits. Transient acute treatment side effects included nausea and vomiting and single occurrences of conjunctivitis/increased tearing and serous tympanitis. CONCLUSION: IMRT in the treatment of central nervous system meningiomas is feasible and safe, offering highly conformal irradiation for complex-shaped skull-base tumors while sparing adjacent critical structures. If the tumor remissions seen here are found in the ongoing treatments, IMRT may be considered the treatment of choice for inoperable or subtotally resected meningiomas and for otherwise difficult-to-treat, complex-shaped tumors of the central nervous system adjacent to critical structures, with the potential of dose escalation for malignant tumors.

Calcification in coronary arteries as quantified by CT scans correlated with tobacco consumption in patients with inoperable non-small cell lung cancer treated with three-dimensional radiotherapy.

It has been shown that radiological manifestations of coronary artery sclerosis are an indirect measure of co-morbidity and predictive of survival. The aim of the present study is to evaluate the outcome and side effects after three-dimensional (3D) radiotherapy in patients with unresectable non-small cell lung cancer (NSCLC) stage I, II and IIIA, depending on coronary artery calcification, Karnofsky performance index (KI) and co-morbidity. Between 1993 and 1999, 89 patients with unresectable NSCLC were treated with 3D-radiotherapy. The median age was 66.6 years and median KI 80%. All patients had 3D-treatment planning, based on CT scans. The median total dose was 60 Gy in 2 Gy fractions five times a week. The mean follow-up period was 13.2 months and mean survival time 12.2 months. Significant prognostic factors for improved survival were KI and tumour stage. Patients with a KI<90% had a median survival of 6.5 months compared with 14 months, in patients with KI>/==" BORDER="0">90% (p<0.001). NSCLC stage I+II showed a significantly longer median survival than patients with NSCLC stage IIIA (16.5 months versus 7 months, p<0.004). A significant correlation was seen between pack-years and coronary artery calcification (p<0.05) and between age and marked coronary artery calcification. The incidence of calcification was 67% in smokers (>/==" BORDER="0">20 pack-years) and 43/58 in patients >60 years (p<0.007). Side effects, e.g. pneumonitis, did not correlate with coronary artery calcification but correlated with chronic obstructive lung disease in 19/89 patients. Conventional CT scans for 3D-treatment planning are able to detect coronary artery calcification. There is a significant correlation between age, KI, tobacco consumption and vascular calcification. Although there was a trend to worse overall survival, coronary artery calcification was not a significant predictor of progression-free and overall survival.

[Intraoperative radiotherapy as part of the treatment concept of soft tissue sarcomas]. / Die intraoperative Strahlentherapie im Behandlungskonzept von Weichteilsarkomen.

The therapy of soft tissue sarcomas is not uniform. The goal of treatment for soft tissue sarcomas is surgical resection with negative microscopic margins. Other therapy options are pre-, intra-, or postoperative radiotherapy as well as neoadjuvantor adjuvant chemotherapy with different drugs, systemic or under local perfusion of the limb. If a margin-free surgical resection is not possible, intraoperative radiation therapy (IORT) offers the possibility for treatment of sites at high risk for local recurrence. The goal of this collaborating study of the Orthopedic University Hospital of Heidelberg and the department of Radio-Oncology of the University Hospital of Heidelberg is to observe the influence of IORT on the rate of local recurrence, complications, metastases, and survival in another wise unchanged tumor management. From 1960 to 1998,78 patients were treated for soft tissue sarcomas; 26 of 78 patients underwent intraoperative radiation and 52 patients were treated without intraoperative radiation. We found a recurrence rate of 15% in the IORT group and 29% in the non-IORT group. No difference for survival or distant recurrence was found, also no difference in early postoperative complication rate, but a higher rate of late complications after IORT (34% vs 7%) was remarkable. We think intraoperative radiation allows better local control and for that reason IORT is integrated into our therapeutic concept. Its influence on survival and distant metastases needs further investigations.

[Computer-assisted reconstruction of coronary vessels]. / Rechnerunterstützte Rekonstruktion von Herzkranzgefässen.

End stage coronary artery disease with linear stenosis of the main vessels despite several coronary interventions is a current challenge for surgical treatment. As the long term results are mainly determined by the pathology of the coronary vessels a simple revascularisation with arterial or venous grafts provides no adequate solution of the problem. An exactly controlled 3D-reconstruction of the coronary vessels enabling selective thrombendarteriectomy (TEA) seems to be a new approach, that may be limited by neointimal hyperproliferation of the coronary vessels. Intraoperative brachytherapy may be a tool to inhibit this process.

Networking in shared care--first steps towards a shared electronic patient record for cancer patients.

OBJECTIVES: This paper aims at identifying the data protection and security requirements for a cross-institutional EPR. Three possible models and the first steps towards a cross-institutional EPR for the Thoraxklinik Heidelberg and the Department of Clinical Radiology of the University Medical Center of Heidelberg shall be discussed. METHODS: A comprehensive analysis of literature and legal documents supplied information for determining the data protection and security requirements. By means of information system analysis, the technical preconditions in both institutions as well as three possible models towards a cross-institutional EPR were identified. RESULTS: According to the German penal code it is only allowed to reveal patient information to external physicians in cases of so-called "treatment connection". An extension of the written consent, signed by the patient, verifying the patient agreement that his/her patient data will be stored in a cross-institutional EPR is needed. Among the three models that we identified, the model that constitutes of a virtual EPR with distributed data capture in both institutions was favored. By means of SecuRemote software a secure connection between the Thoraxklinik Heidelberg and the Department of Clinical Radiology was established, allowing the physicians to view the complete cross-institutional health information of a jointly treated patient during the weekly consultation on radiotherapy. CONCLUSIONS: Many requirements listed in this paper are requirements for electronic patient records in general. Besides these general requirements there are specific requirements for a cross-institutional EPR. The legal situation in Germany complicates the development and implementation of a cross-institutional EPR. However, we think that the efforts are reasonable, because a cross-institutional EPR will be able to improve the communication between health institutions, medical disciplines and persons involved in shared care processes. It provides them with more complete health information about the jointly treated patients. A cross-institutional EPR is, therefore, expected to improve the quality of patient care.

Radiation recall dermatitis from docetaxel.

BACKGROUND: Experiences with inflammatory skin reactions after treatment with docetaxel and prior exposure to radiotherapy like a recall phenomenon are very rare. We present the case of an uncommon and severe skin reaction after docetaxel application and prior radiotherapy. PATIENT AND METHODS: A 40-year-old female was treated with an upper body irradiation with electrons because of relapsed breast cancer. In addition, because of metastases of brain and bone she received radiotherapy on the whole brain and the left pelvis. One week after radiotherapy weekly chemotherapy with docetaxel was started. RESULTS: Radiotherapy was well tolerated. There was a cutaneous erythema RTOG grade 1. After second application of docetaxel the patient developed a severe skin erythema, after fourth application confluent desquamations exactly demarcated the previously irradiated skin area. After discontinuation of docetaxel and after antiinflammatory treatment the skin reactions improved rapidly. CONCLUSION: In our opinion the severe skin reaction was clearly associated with the application of docetaxel like a recall phenomenon after previous radiotherapy. In case of severe skin reaction after this therapy it is important to know the possibility of recall phenomenon.

Dose-dependent differential effects of low and pulsed dose-rate brachytherapy in a radioresistant syngenic rat prostate tumour model.

PURPOSE: To study the response of the Dunning prostate carcinoma (R3327-AT1 subline) to continuous low dose-rate (CLDR) and pulsed dose-rate (PDR) brachytherapy. MATERIALS AND METHODS: After subcutaneous tumour transplantation into the thigh of the Copenhagen rat, doses of 0, 20, 30, 40 and 50 Gy were applied to the tumour surface (tumour diameter 9+/-1mm). Eight animals were irradiated per dose group and exposure condition. Interstitial PDR ((192)Ir source, 37 GBq) and CLDR ((192)Ir seed, 150 MBq) brachytherapy were carried out with 0.75 Gy/pulse h(-1) and a dose-rate of 0.75Gyh(-1), respectively. Treatment response was assessed in terms of growth delay expressed as the time (T(5)) required for each tumour to reach five times the initial tumour volume. RESULTS: The median T(5) times for the CLDR groups (in the order: control, 20, 30, 40, 50 Gy) were 12 (12), 54.5 (21), 64.5 (31), 85.5 (51), and 65 (47.5) days. Values after PDR brachytherapy are given in parentheses and resulted in a significantly impaired tumour growth delay (log-rank test) in the 20Gy (p =0.006) and 30 Gy (p =0.036) groups. No significant difference was found in the 40-50 Gy dose range. CONCLUSIONS: In contrast to previous results and predictions of biological models we observed dose-dependent differential effects of PDR and CLDR brachytherapy with reduced efficacy of PDR in the lower dose range.

[Organ preservation in advanced laryngeal and hypopharyngeal carcinoma by primary radiochemotherapy. Results of a multicenter phase II study]. / Organerhalt beim fortgeschrittenen Larynx- bzw. Hypopharynxkarzinom durch primäre Radiochemotherapie. Ergebnisse einer multizentrischen Phase-II-Studie.

INTRODUCTION: Regarding the promising results of international trials we conducted the first German prospective multicentre phase II trial for organ preservation with primary simultaneous chemoradiation in advanced laryngeal and hypopharyngeal cancer. PATIENTS AND METHODS: 28 of 30 recruited patients suffering from stage II and III (UICC) laryngeal and hypopharyngeal cancer were treated with primary simultaneous chemoradiation within an organ preservation program and monitored in follow-up of one year. Exclusion criteria included tumor infiltration of the laryngeal cartilage, bilateral neck nodes (N2c) and need for flap reconstruction in case of laryngectomy. The protocol included an accelerated concomitant boost chemoradiation (66 Gy) with Carboplatinum (70 mg/m2 1st and 5th week) and a restaging procedure one month after therapy. In case of residual disease, salvage laryngectomy and/or neck dissection were performed. RESULTS: After follow-up of one year 20 of 28 patients (71%) were presented with stable complete remission and functionally preserved larynx. Of these 20 patients 3 developed pulmonary metastases, 1 secondary primary carcinoma of the lung and 3 neck metastases which needed neck dissections. The other patients showed in 4 cases relapsing tumor which was indicated for laryngectomy. One patient needed tracheotomy because of persisting edema and 2 patients died due to tumor progress. One patient died after complications due to salvage surgery. CONCLUSION: The organ preservation protocol was feasible with well tolerated early toxicity. Problems of screening for recurrent disease, salvage surgery and late toxicity should be noted and pronounced in patient information. Further studies should focus on the improvement of patient selection which could be realized by induction Chemotherapy (using new components like taxan) and/or use of prediction factors such as tumor volume and hemoglobin levels.

Comparison of forward planned conformal radiation therapy and inverse planned intensity modulated radiation therapy for esthesioneuroblastoma.

The purpose of this study was to compare dose distribution of inverse planned intensity modulated radiation therapy (IMRT) with that of conformal radiation therapy (SCRT) in the treatment of esthesioneuroblastoma, and to report initial clinical results. 13 patients with esthesioneuroblastoma were planned both with IMRT and SCRT using complete three-dimensional data sets. A target dose of 60 Gy was prescribed. We performed a detailed dose volume histogram analysis. Dose coverage was equal in both plans while dose distribution was more conformal to the target volume with IMRT. Mean and maximum dose of the brain stem, chiasm, optic nerves and orbits were lower using IMRT than SCRT. The reduction was significant regarding orbit and optic nerve (p<0.05). IMRT was superior in sparing of organs at risk compared with SCRT. The additional sparing by IMRT was positively correlated to the size of the target volume, which was evident with target volumes above 200 cm3. Treatment time was approximately 20 minutes per fraction using IMRT compared with 15 minutes per fraction using SCRT. We conclude that IMRT is both feasible and a valuable tool for more conformal dose distribution in the treatment of esthesioneuroblastoma and to spare organs at risk that are in critical relationship to the tumour. This advantage could be seen especially well in complex shaped target volumes above 200 cm3. Thus, using IMRT, risk of complications may be minimized and local tumour control may be increased.