[Stereotactic body radiation therapy: radiobiological characteristics, physical-technical prerequisites, clinical applications]. / Extrakranielle Stereotaxie: strahlenbiologische Besonderheiten, physikalisch-technische Voraussetzungen, klinische Einsatzmöglichkeiten.

Radiotherapy of small targets with very high single doses administered in 1 to approximately 12 fractions-carried out under image guidance and with the intention of "tumour ablation"-is called stereotactic body radiation therapy (SBRT) for extracranial tumours or metastases. Radiobiologically, besides damaging the DNA of the tumour cells, the tumour vessels are also occluded and immunological effects are triggered. The safe performance of SBRT requires a very high physical-technical effort in order to ensure sufficient protection of healthy organs. Clinically, SBRT offers a wide range of applications in curative therapy (e.g. non-small-cell lung cancer stage I). Furthermore, it is a conservative, effective and well-tolerated option for the treatment of individual metastases and an optimal combination partner in the therapy of oligometastatic tumours.

Low-dose external beam radiotherapy for greater trochanteric pain syndrome : Target volume definition and treatment outcome.

PURPOSE: Low-dose external beam radiotherapy (ED-EBRT) is frequently used in the therapy of refractory greater trochanteric pain syndrome (GTPS). As studies reporting treatment results are scarce, we retrospectively analyzed our own patient collectives. PATIENTS AND METHODS: In all, 60 patients (74 hips) received LD-EBRT (6 × 0.5 Gy in 29 hips, 6 × 1 Gy in 45). The endpoint was the patient's reported subjective response to treatment. The influence of different patient and treatment characteristics on treatment outcome was investigated. RESULTS: At the end of LD-EBRT, 69% reported partial remission, 4% complete remission, no change 28%. A total of 3 months later (n = 52 hips), the results were 37, 33, and 30% and 18 months after LD-EBRT (n = 47) 21, 51, and 28%. In univariate analysis "inclusion of the total femoral head into the PTV" and "night pain before LD-EBRT" were correlated with symptom remission at the end of LD-EBRT, while "initial increase in pain during LD-EBRT" was significantly associated with treatment failure. In multivariable modeling "initial increase in pain" was identified as a risk factor for treatment failure (p = 0.007; odds ratio [OR] 0.209; 95% confidence interval [CI] 0.048-0.957), while "night pain" was an independent factor for remission (p = 0.038; OR 3.484; 95% CI 1.004-12.6). Three months after LD-EBRT "night pain" and "inclusion of the complete femoral neck circumference into the PTV" were predictive for remission. CONCLUSION: LD-EBRT represents a useful treatment option for patients suffering from GTPS. Three months after therapy two-thirds of the patients reported a partial or complete symptom remission. Especially patients who suffered from nocturnal pain seemed to benefit. Treatment appeared to be more effective when the entire circumference of the femoral neck was encompassed.

The field size matters: low dose external beam radiotherapy for thumb carpometacarpal osteoarthritis : Importance of field size.

The purpose of this work was to evaluate the efficacy of low-dose radiotherapy (RT) for thumb carpometacarpal osteoarthritis (rhizarthrosis). The responses of 84 patients (n = 101 joints) were analyzed 3 months after therapy (n = 65) and at 12 months (n = 27). Patients were treated with 6 fractions of 1 Gy, two times a week, with a linear accelerator. At the end of therapy, about 70 % of patients reported a response (partial remission or complete remission), 3 months later about 60 %, and 1 year after treatment 70 %. In univariate regression analysis, higher patient age and field size greater than 6 × 4 cm were associated with response to treatment, while initial increase of pain under treatment was predictive for treatment failure. Duration of RT series (more than 18 days), gender, time of symptoms before RT, stress pain or rest pain, or prior ortheses use, injections, or surgery of the joint were not associated with treatment efficacy. In multivariate regression analysis, only field size and initial pain increase were highly correlated with treatment outcome. In conclusion, RT represents a useful treatment option for patients suffering from carpometacarpal osteoarthritis. In contrast to other benign indications, a larger field size (>6 × 4 cm) seems to be more effective than smaller fields and should be evaluated in further prospective studies.

Tangential vs. defined radiotherapy in early breast cancer treatment without axillary lymph node dissection: a comparative study.

PURPOSE: Recent studies have demonstrated low regional recurrence rates in early-stage breast cancer omitting axillary lymph node dissection (ALND) in patients who have positive nodes in sentinel lymph node dissection (SLND). This finding has triggered an active discussion about the effect of radiotherapy within this approach. The purpose of this study was to analyze the dose distribution in the axilla in standard tangential radiotherapy (SRT) for breast cancer and the effects on normal tissue exposure when anatomic level I-III axillary lymph node areas are included in the tangential radiotherapy field configuration. PATIENTS AND METHODS: We prospectively analyzed the dosimetric treatment plans from 51 consecutive women with early-stage breast cancer undergoing radiotherapy. We compared and analyzed the SRT and the defined radiotherapy (DRT) methods for each patient. The clinical target volume (CTV) of SRT included the breast tissue without specific contouring of lymph node areas, whereas the CTV of DRT included the level I-III lymph node areas. RESULTS: We evaluated the dose given in SRT covering the axillary lymph node areas of level I-III as contoured in DRT. The mean VD95% of the entire level I-III lymph node area in SRT was 50.28% (range, 37.31-63.24%), VD45 Gy was 70.1% (54.8-85.4%), and VD40 Gy was 83.5% (72.3-94.8%). A significant difference was observed between lung dose and heart toxicity in SRT vs. DRT. The V20 Gy and V30 Gy of the right and the left lung in DRT were significantly higher in DRT than in SRT (p<0.001). The mean heart dose in SRT was significantly lower (3.93 vs. 4.72 Gy, p=0.005). CONCLUSION: We demonstrated a relevant dose exposure of the axilla in SRT that should substantially reduce local recurrences. Furthermore, we demonstrated a significant increase in lung and heart exposure when including the axillary lymph nodes regions in the tangential radiotherapy field set-up.

Radiotherapy of Breast Cancer in Laterally Tilted Prone vs. Supine Position: What about the Internal Mammary Chain?

BACKGROUND: In the multimodal breast-conserving curative therapy of some high-risk breast cancer patients, extended external beam radiotherapy (EBRT) not only to the breast but also to the supraclavicular fossa and the internal mammary chain (parasternal region (PSR)) is indicated. We report a dosimetric study on the EBRT of the breast ("B") and the breast including PSR ("B + PSR"), comparing the supine and the laterally tilted prone patient positions in free breathing. METHODS: The planning CT scans of 20 left- and 20 right-sided patients were analyzed. EBRT plans were calculated with 3D conformal EBRT (3D) and with intensity-modulated EBRT (IMRT) for "B" and "B + PSR" in the prone and supine positions. The mean and threshold doses were computed. The quality of EBRT plans was compared with an overall plan assessment factor (OPAF), comprising three subfactors, homogeneity, conformity, and radiogenic exposure of OAR. RESULTS: In the EBRT of "B", prone positioning significantly reduced the exposure of the OARs "heart" and "ipsilateral lung" and "lymphatic regions". The OPAF was significantly better in the prone position, regardless of the planning technique or the treated breast side. In the EBRT of "B + PSR", supine positioning significantly reduced the OAR "heart" exposure but increased the dose to the OARs "ipsilateral lung" and "lymphatic regions". There were no significant differences for the OPAF, independent of the irradiated breast side. Only the IMRT planning technique increased the chance of a comparatively good EBRT plan. CONCLUSION: Free breathing prone positioning significantly improves plan quality in the EBRT of the breast but not in the EBRT of the breast + PSR.

Comparison of the micronucleus and chromosome aberration techniques for the documentation of cytogenetic damage in radiochemotherapy-treated patients with rectal cancer.

PURPOSE: The goal of the interdisciplinary Clinical Research Unit KFO179 (Biological Basis of Individual Tumor Response in Patients with Rectal Cancer) is to develop an individual Response and Toxicity Score for patients with locally advanced rectal cancer treated with neoadjuvant radiochemotherapy. The aim of the present study was to find a reliable and sensitive method with easy scoring criteria and high numbers of cell counts in a short period of time in order to analyze DNA damage in peripheral blood lymphocytes. Thus, the cytokinesis-block micronucleus (CBMN) assay and the chromosome aberration technique (CAT) were tested. MATERIALS AND METHODS: Peripheral blood lymphocytes obtained from 22 patients with rectal cancer before (0 Gy), during (21.6 Gy), and after (50.4 Gy) radiochemotherapy were stimulated in vitro by phytohemagglutinin (PHA); the cultures were then processed for the CBMN assay and the CAT to compare the two methods. RESULTS: A significant increase of chromosomal damage was observed in the course of radiochemotherapy parallel to increasing radiation doses, but independent of the chemotherapy applied. The equivalence of both methods was shown by Westlake's equivalence test. CONCLUSION: The results show that the CBMN assay and the CAT are equivalent. For further investigations, we prefer the CBMN assay, because it is simpler through easy scoring criteria, allows high numbers of cell counts in less time, is reliable, sensitive, and has higher statistical power. In the future, we plan to integrate cytogenetic damage during radiochemotherapy into the planned Response and Toxicity Score within our interdisciplinary Clinical Research Unit.

Moderately Hypofractionated Intensity-modulated Radiotherapy With a Simultaneous Integrated Boost for Locally Advanced Head and Neck Cancer - Do Modern Techniques Fulfil Their Promise?

BACKGROUND: Intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) and moderate hypofractionation offers an opportunity for defining individual doses and a reduction in overall treatment time in locally advanced head and neck cancer (HNSCC). We present retrospective data on toxicity and locoregional control of a patient cohort treated with an IMRT-SIB concept in comparison to normo-fractionated 3D-conformal radiotherapy (3D-RT). PATIENTS AND METHODS: Between 2012 and 2014, 67 patients with HNSCC (stages III-IVB) were treated with IMRT-SIB either definitively or in the postoperative setting. These patients were matched with those of patients treated with normo-fractionated 3D-RT before mid-2012 and their clinical courses were compared. Chemotherapy or cetuximab was given concomitantly in both groups in the definitive situation (postoperatively, dependent on risk factors). RESULTS: Significantly less toxicity was found in favor of IMRT-SIB concerning dysphagia, dermatitis, xerostomia, fibrosis, and lymphedema. After a median follow-up of 31 months (range=2-104 months), 3-year locoregional control was 73% for those treated with IMRT-SIB versus 78% for those treated with 3D-RT. CONCLUSION: This moderately hypofractionated IMRT-SIB concept was shown to be feasible, incurring less toxicity than conventional 3D-RT.

Prospective Evaluation of Low-Dose External Beam Radiotherapy (LD-EBRT) for Painful Trapeziometacarpal Osteoarthritis (Rhizarthrosis) on Pain, Function, and Quality of Life to Calculate the Required Number of Patients for a Prospective Randomized Study.

Background: Retrospective studies have described the effectiveness of low-dose radiotherapy (LD-EBRT) in painful arthrosis of small finger joints, but two recent prospective studies have yielded ambiguous results. To generate accurate data for the planning of a trial, we conducted a prospective, monocentric, observational study to describe the effects of LD-EBRT as precisely as possible. Methods: Twenty-five consecutive patients with symptomatic trapeziometacarpal (TMC) arthrosis were irradiated with 6 × 0.5 Gy. Before, 3, and 12 months after LD-EBRT, we assessed subjective endpoints (modified "von-Pannewitz score", 10-point visual analogue scale (VAS), "patient-rated wrist evaluation" (PRWE)), and objective measurements ("active range of motion" (AROM), Kapandji index, grip strength, pinch grip). Results: At 3/12 months, 80%/57% reported partial and 4%/18% complete remission according to the "von-Pannewitz" score. VAS "overall pain" significantly decreased from a median of seven (IQR 4) at baseline to three (IQR 6; p = 0.046) and to two (IQR 2; p = 0.013). Similar results were obtained for VAS "pain during exercise", VAS "pain during daytime", and VAS "function". "PRWE overall score" was reduced from 0.5 at baseline (SD 0.19) to 0.36 (SD 0.24, p = 0.05) and to 0.27 (SD 0.18, p = 0.0009). We found no improvements of the objective endpoints (AROM, Kapandji, grip strength) except for flexion, which increased from 64° (SD 12°) at baseline to 73° (SD 9.7°, p = 0.046) at 12 months. Conclusions: We recommend the PRWE score as a useful endpoint for further studies for this indication. To prove a 15% superiority over sham irradiation, we calculated that 750 patients need to be prospectively randomized.

Dupuytren's Disease-Etiology and Treatment.

BACKGROUND: The worldwide prevalence of Dupuytren's disease (DD) is 8%. DD is a chronic disease for which there is no cure. Various treatments are available. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed and Embase. RESULTS: Genetic factors account for 80% of the factors involved in causing this disease. Diabetes mellitus, hepatic diseases, epilepsy, and chronic occupational use of vibrating tools are also associated with it. Limited fasciectomy is the most common treatment and is considered the reference standard. Possible complications include persistent numbness in areas where the skin has been elevated, cold sensitivity, and stiffness, with a cumulative risk of 3.6 -39.1% for all complications taken together. The recurrence rate at 5 years is 12-73%. Percutaneous needle fasciotomy is the least invasive method, with more rapid recovery and a lower complication rate than with limited fasciectomy. 85% of patients have a recurrence after an average of 2.3 years. Radiotherapy can be given before contractures arise in patients with high familial risk, or postoperatively in selected patients with a very high individual risk of recurrence. CONCLUSION: Although DD is not curable, good treatments are available. Recurrences reflect the pathophysiology of the disease and should not be considered complications of treatment. When counseling patients about the available treatment options, particularly the modalities and timing of surgery, the physician must take the patient's degree of suffering into account. Nowadays, fast recovery from surgery and less postoperative pain are a priority for many patients. Different surgical methods can be used in combination. It remains difficult to predict the natural course and the time to postoperative recurrence in individual patients; these matters should be addressed in future studies.