[Radiation therapy for prostate cancer in the new S3 guideline. Part 1: localized and locally advanced prostate cancer]. / Strahlentherapie des Prostatakarzinoms in der neuen S3-Leitlinie. Teil 1: Lokal begrenztes und lokal fortgeschrittenes Prostatakarzinom.

Radiation therapy is a treatment option for curative management of localized and locally advanced prostate cancer. Depending on tumor stage and constellation of risk factors (PSA level, findings on digital rectal examination, and Gleason score), various forms of radiotherapy are applied. In addition to the sole use of external beam radiotherapy, brachytherapy with radioactive seeds is also employed as stand-alone treatment in patients with low risk factors and in early clinical stages. Increasing risk of recurrence requires more intensive therapies which can be accomplished by adding hormone deprivation therapy and/or intensifying radiation therapy (dose escalation). Combined approaches using brachytherapy and percutaneous radiotherapy are also initiated in these cases. If hormone ablation therapy is administered, this should occur over a course of 3-36 months as neoadjuvant, concommitant and/or adjuvant treatment, depending on the risk of recurrence.

[Radiation therapy for prostate cancer in the new S3 guideline. Part 2: postoperative radiation therapy and brachytherapy]. / Strahlentherapie des Prostatakarzinoms in der neuen S3-Leitlinie. Teil 2: Postoperative Strahlentherapie und Brachytherapie.

Postoperative adjuvant radiation therapy has achieved special significance based on the results of three randomized studies on stage pT3R1 prostate cancer which provided evidence for prolonged survival in comparison to the "wait and see" strategy. When PSA levels persist or increase after radical prostatectomy, irradiation represents an alternative. In this instance, salvage radiotherapy should be initiated as early as possible, most suitably when the PSA level is <0.5 ng/ml. Side effects of percutaneous radiotherapy using modern techniques are minimal in this stage; severe grade 3 or 4 late sequelae occur in <3% of cases. Low dose rate (LDR) brachytherapy as monotherapy is a primary treatment option for low-risk tumors. In patients with intermediate-risk tumors, data are controversial and cannot be assessed conclusively. LDR brachytherapy should not be administered in high-risk tumors. High dose rate (HDR) brachytherapy combined with percutaneous radiotherapy as an example of a typical dose escalation approach is a primary option for intermediate- and high-risk prostate cancer. Whether additional hormone therapy is needed with HDR brachytherapy is unclear. HDR monotherapy can only be recommended in the clinical trial setting.

Shared decision-making--results from an interdisciplinary consulting service for prostate cancer.

Locally confined prostate cancer (PCa) can be treated by various treatment options (e.g. radical prostatectomy or radiation therapy) with comparable results but different possible side effects. Therefore, treatment recommendations can vary between urologists and radiation oncologists. In 2001 the Charite-Campus Benjamin Franklin (CBF, Berlin), established the first interdisciplinary consulting service for prostate cancer patients in Germany. The aim was to offer a comprehensive and neutral consultation on all treatment options and to make treatment recommendations. The study examines what benefits may be derived from this type of consultation. A total of 362 patients presented to the consulting service between May 2001 and April 2003. Two questionnaires were used. The first one contained epidemiological questions as well as questions covering information already available on PCa. It also examined feelings and fears about the disease and possible treatment options. The second questionnaire was completed 2 weeks after the consultation to evaluate the treatment decision, determine the patient's satisfaction with the consultation and trace the development of feelings and fears. Of the patients, 334 (92.2%) were completely assessable. All patients had already obtained information about the disease and possible treatment options and wished to be involved in the decision-making process through objective and neutral consultation. Nearly all of them had a great fear of the possible side effects of therapy. Such a comprehensive consultation is time-consuming (average of 35 min) but largely received a very positive assessment in that a total of 66% found it either helpful (n=74, 22%) or very helpful (n=147, 44%). Patients felt they had been completely informed in 92% of the cases. Only 22 (9.7%) had still failed to make a decision after 2 weeks, 115 patients had stage T1c, PSA <10 ng/ml and a Gleason score < or =7. In these cases an equivalent recommendation for radical prostatectomy, percutaneous radiotherapy or permanent seed implantation was given. Of these, 49 (43.4%) decided on the surgical intervention, 48 (42.5%) on a type of radiotherapy and only 18 (15.6%) remained undecided. The histological examination of prostatectomy specimens from patients who had decided to undergo radical surgery at CBF showed a significant decrease in the rate of extracapsular disease extension (> or =T3) from 38% to 20% during the observation period. The interdisciplinary approach has made the process of deciding on an appropriate treatment much easier for the patient. The time-consuming consultation enables better selection of individual treatment modalities and their possible side effects from the point of view of both the patients and the attending physicians. In this study, patients chose either radical surgery or radiotherapy with equal frequency.

Catheter based intracoronary brachytherapy leads to increased platelet activation.

BACKGROUND: Vascular brachytherapy (VBT) after percutaneous coronary intervention (PCI) is associated with a higher risk of stent thrombosis than conventional treatment. OBJECTIVE: To investigate in vivo periprocedural platelet activation with and without VBT, and to assess a possible direct effect of radiation on platelet activation. DESIGN: Of 50 patients with stable angina, 23 received VBT after PCI, while 27 had PCI only. The 23 patients who received VBT after PCI were pretreated for one month with aspirin and clopidogrel. Platelet activation was assessed by flow cytometry. RESULTS: The two patient groups did not differ in their platelet activation before the intervention. There was a significant increase in activation immediately after VBT, with 21.2% (interquartile range 13.0% to 37.6%) thrombospondin positive and 54.0% (42.3% to 63.6%) CD 63 positive platelets compared with 12.7% (9.8% to 14.9%) thrombospondin positive and 37.9% (33.2% to 45.2%) CD 63 positive platelets before the intervention (p < 0.001 and p < 0.01, respectively). Patients without VBT had no periprocedural difference in platelet activation immediately after PCI. No increase in platelet activation was found after ex vivo irradiation of blood samples obtained from healthy controls. CONCLUSIONS: Catheter based intracoronary VBT carried out according to current standards is highly thrombogenic. The current antithrombotic treatment with aspirin and clopidogrel is not sufficient to suppress platelet activation during the procedure. From in vitro experiments, it appears that platelet activation during brachytherapy is not caused by irradiation but by the procedure of catheter based VBT.

A pilot study of irinotecan (CPT-11) as single-agent therapy in patients with locally advanced or metastatic esophageal carcinoma.

BACKGROUND AND AIMS: This study assessed the efficacy and safety of irinotecan (CPT-11) in the treatment of patients with unresectable esophageal carcinoma. PATIENTS AND METHODS: Ten patients with esophageal squamous cell carcinoma (SCC) and three with adenocarcinoma (AC) were treated with CPT-11. Eight of the 13 patients were pretreated by surgery, radio-, or chemotherapy. CPT-11 was administered in repeated 6-week cycles consisting of CPT-11 once weekly for 4 weeks, followed by a 2-week rest. The starting dose of CPT-11 was 125 mg/m(2) given intravenously over 60 min; subsequent doses were adjusted based on tolerance and toxicity. Nine patients were evaluable for response. RESULTS: Two patients showed a partial response (one SCC, one AC) and two others disease stabilization (one SCC, one AC). The mean time to progression was 3.8 months. Mean survival since study entry was 6.1 months. In the 103 administrations we observed grade 3 or 4 toxicity on six occasions with diarrhea, five with neutropenia, and one with nausea and vomiting. Toxicity required dose reductions in five patients; in two of these patients treatment was stopped because of severe toxicity. No treatment related deaths occurred. CONCLUSION: CPT-11 as single-agent therapy is modestly effective against squamous cell cancer of the esophagus.

Adjuvant and salvage radiotherapy after radical prostatectomy.

BACKGROUND: Following radical prostatectomy, between 15 and 60% of all patients with pT3 prostate cancer experience persistence or increasing levels of prostate-specific antigen (PSA) as a sign of tumor persistence or progression within 5 years. Retrospective studies have shown a rate of 35-55% of positive biopsies from the vesicourethral anastomosis in this situation. Best treatment for these disease conditions is under debate, current strategies include adjuvant radiotherapy (RT), 'wait-and-see' and salvage RT or hormone therapy for increasing PSA. RESULTS: A number of retrospective studies have shown an increased rate of local control and 'freedom from treatment failure' following adjuvant RT with doses in the range of 50-60 Gy. However, no survival benefit could be demonstrated by now. Results of three major phase III studies are pending. In case of persisting or increasing PSA levels following radical prostatectomy, 30-70% of these patients will reach an undetectable PSA level after conformal RT with total doses of 60-70 Gy, which will stay undetectable or at least stable within the next 2-5 years in about 50% and therefore offering a chance of cure. When starting RT, PSA should be as low as possible (<2 ng/ml). With higher PSA levels the chance of achieving an undetectable PSA again decreases below 35%. High Gleason scores of 8-10, seminal vesicle involvement and a short PSA doubling time are adverse prognostic factors. Severe late side effects of conformal RT are infrequent (<3%). In contrast, hormonal treatment is of palliative nature in the long run, with a median time to development of metastases of 4-7 years, and can be offered to patients with progressive disease after RT. CONCLUSIONS: Adjuvant RT following radical prostatectomy for pT3 prostate cancer offers higher local control rates and an increase in 'freedom from treatment failure', but no prolongation of survival has yet been shown. In the situation of increasing PSA levels after radical prostatectomy, salvage RT seems to offer a chance of cure in selected patients, although it is difficult to draw firm conclusions because of generally too short follow-up times.

Interstitial brachytherapy with permanent seed implants in early prostate cancer.

Excellent clinical results after permanent seed implantation have been reported by various centers in large cohorts of patients. However, all of these had extensive experience in this special field of radiotherapy and the therepy and the follow-up time is too short for definite conclusions. The fact that this option of treatment can be carried out on an outpatient basis and that it allows to get the patient back to normal as far as social environment and work are concerned, has led to wide acceptance of this particular mode of therapy. Therefore, permanent seed implantation is a possible treatment option for localized prostate cancer and can be offered to patients with T1- T2a tumors, PSA levels of < 10 and a Gleason score of < 7. By using permanent seed implantation in these selected patients, it seems possible to achieve results comparable with surgery alone or percutaneous, 3D-planned radiotherapy.

[Osteoradionecrosis after radiotherapy for gynecologic tumors]. / Osteoradionekrose nach Strahlentherapie gynäkologischer Tumoren.

AIM: Insufficiency fractures of the pelvis are a well known but rare and frequently misinterpreted radiation sequela. The clinical features and possible risk factors were investigated. PATIENTS AND METHODS: 71 of living 82 patients, who were treated 1986-1994 for gynecologic tumors were clinically examined. 47 patients underwent also bone scan, CT of the pelvis and 13 patients had osteodensitometry. All patients had been treated with adjuvant (n = 29) or curative intent (n = 18) by d.v. fields with 18-MV photons, with 46 Gy in 23 fractions plus brachytherapy (15-39 Gy). Median follow-up was 36 months. RESULTS: Seven patients developed pelvic insufficiency fractures 11 months (median, minimum 2 months) after treatment. All patients complained of moderate to severe pelvic pain, which resolved after 5-28 months without specific therapy in five of seven patients. At first examination all but one bone scan showed extremely increased uptake in the os sacrum and/or iliosacral joints, correlating CT scans demonstrated small fractures and bony destruction. Four of the asymptomatic 40 patients with complete radiologic examinations had medium uptake in bone scan (CT normal). Three of four examined patients with insufficiency fractures and seven of nine patients without insufficiency fractures had osteoporosis. CONCLUSION: In women who present with pelvic pain after radiotherapy for gynecologic tumors bony destruction and fractures may be indicative of a late radiation effect rather than osseous metastasis, even after early onset of symptoms.

[Radiotherapeutic strategies in the multimodal therapy of resectable and nonresectable pancreatic carcinoma]. / Strahlentherapeutische Strategien in der multimodalen Therapie des resektablen und nicht resektablen Pankreaskarzinoms.

BACKGROUND: The prognosis of patients with adenocarcinoma of the pancreas remains poor. Only patients with small tumors and complete resection have a curative chance. The value of combined radio-chemotherapy adjuvant or even palliative in case of unresectable tumors is controversial due to the short median survival times of all patients ranging from 8 to 15 months. Within the last years, significant new treatment modalities were introduced into the multimodality approach. Even the intraoperative boost therapy (IORT) with fast electrons remains still controversial. MATERIAL AND METHODS: Since the publication of the results of the historic GITSG study, in the US postoperative adjuvant radio-chemotherapy with 5-FU remains the treatment of choice. Successor studies of the ESPAC and the EORTC have been closed or are recruiting patients, the results are still pending. Neoadjuvant treatment modalities were investigated within the last 3 years, mostly in case of primary operable but also in unresectable tumors. Using 3-D-treatment planning, the total dose of radiotherapy was increased from 40 up to 45 to 50 Gy. In centers with great experience, an IORT was added to these combined modalities. More modern chemotherapeutic agents like gemcitabine or the taxanes are under investigation, using combined radio-chemotherapy in phase-II protocols in patients with unresectable tumors. RESULTS: In case of both, adjuvant or neoadjuvant radio-chemotherapy following or before pancreaticoduodenectomy, median survival times range from 15 to 25 months. The neoadjuvant radio-chemotherapy seems to reduce the rate of positive surgical margins and the rate of patients with positive lymph nodes. For the moment, there is no proven survival advantage or increase of local control (about 80% in both cases) for patients treated with neoadjuvant radio-chemotherapy compared with adjuvant radio-chemotherapy. However, about 25% of the patients don't receive adjuvant therapy due to the perioperative morbidity. Because prolongation of survival with adjuvant therapy is only 5 to 10 months, in Europe adjuvant radio-chemotherapy is not accepted as the treatment standard. Combined radio-chemotherapy in patients with unresectable tumors results in significant improvement of survival. 5-FU continuous infusion with 250 mg/m2 seems to be the treatment of choice. IORT is effective in achieving long-term local control and an effective pain palliation. More modern chemotherapeutic agents seem to be effective in vitro as radio-sensitizers. In first reported results, the MTD was not found. Toxicity seems not to be increased with single radiotherapy doses of 1.8 to 2 Gy. However, higher single doses should not be used. CONCLUSIONS: Due to the worse prognosis of patients with adenocarcinoma of the pancreas, new combined treatment modalities as adjuvant and neoadjuvant radio-chemotherapy, particularly with more modern chemotherapeutic agents, for patients with resectable and unresectable tumors are under investigation. For some reasons, the neoadjuvant setting seems to be better. However, these results are not proven by prospective randomized clinical trials. Therefore, these trials are necessary to define the treatment of choice in these patients. IORT is a helpful tool to improve local control. However, these aggressive multimodality approaches are only indicated in a minority of patients. In patients with unresectable tumors and good condition, combined radio-chemotherapy remains the treatment of choice.

Radiotherapy of Choroidal Metastases in Patients with Disseminated Cancer.

BACKGROUND: Choroidal metastasis is the most common ocular tumor, in most cases related to breast and lung cancer. Radiotherapy (RT) mostly is the therapy of choice. However, there is a lack of data about the results of uniformly, prospective treated patients. PATIENTS AND METHODS: Between November 1994 and September 1997, 37 patients with 49 metastatic eyes were enrolled into the study. 25 patients (68%) had unilateral and 12 patients (32%) had bilateral metastases. 21 patients had breast cancer as primary tumor, 12 patients lung cancer, and 4 patients other tumors. 3 patients were excluded from analysis, 34 patients with 46 involved eyes were available for analysis. 29 of those patients had symptomatic metastases, 5 patients had asymptomatic choroidal metastases. RT was performed with bi- or unilateral asymmetric fields, total dose was 40 Gy with a single dose of 2 Gy, 5 fractions per week. 12 patients (35%) had a chemotherapy following RT due to diagnosis of general tumor progression. Endpoints of the study were visual acuity (VA), local tumor control, survival, and side effects. RESULTS: The median follow up was 6 months, 22 out of 34 patients died of metastatic disease. In 17 of symptomatic eyes (53%) an increase of VA and in 11 of symptomatic eyes (34%) a 'no change' was achieved. The local tumor control rate after 18 months was 83%. One patient with asymptomatic metastasis (1/14 eyes) developed symptoms until death. The median survival time was 15 months. Altogether, in 2 patients late side effects (6%) were observed (1 patients with bilateral retinopathy, 1 patient with optic nerve atrophy). CONCLUSIONS: RT with 40 Gy is highly effective in the treatment of symptomatic and asymptomatic choroidal metastases, VA was stable or improved in almost 90% of treated eyes. The rate of side effects is low. Copyright 2000 S. Karger GmbH, Freiburg

Accelerated hyperfractionated radiotherapy in 149 patients with glioblastoma multiforme.

Between August 1986 and December 1997, 149 patients with glioblastoma were treated postoperatively with 1.5 Gy fractions three times daily to a total dose of 54 Gy with 4-h intervals. Median actuarial survival was 8.8 months. Survival was 31% at 12 months and 4% at 24 months. No severe acute toxicity occurred. Multivariate analysis revealed that only age < or = 60 years and lactate dehydrogenase levels < or = 240 U/l predicted significantly higher survival probabilities.

Radiotherapy of unilateral choroidal metastasis: unilateral irradiation or bilateral irradiation for sterilization of suspected contralateral disease?

Radiotherapy is the highly effective standard in the treatment of choroidal metastasis. Visual acuity can be stabilized or increased in about 70-80% of eyes treated, thus prevailing the quality of life in these worse prognostic patients. In about 30-40% bilateral macroscopic disease is found at diagnosis. The best treatment for unilateral metastasis remains controversial: unilateral or bilateral irradiation for sterilization of suspected contralateral metastasis or unilateral irradiation without irradiation of the contralateral choroidea. In the analysis of a prospective study (ARO 95-08) 35 out of 50 patients with choroidal metastasis had unilateral disease and received unilateral irradiation with a lateral field using 6 MeV-photons (40 Gy in 20 fractions) without sparing the contralateral choroidea. Therefore the posterior contralateral choroidea received 50-70% of the total dose (20-28 Gy) for suspected micrometastasis. None of these patients developed contralateral choroidal metastasis during the median follow up time of 11.5 months. A unilateral field with 40 Gy for unilateral choroidal metastasis without sparing the contralateral choroidea seems to be effective in destroying contralateral micrometastasis with a lower risk of late side effects compared with bilateral fields.

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.