The Role of Postoperative Radiotherapy for Carcinosarcoma of the Uterus.

The role of postoperative radiotherapy delivered as external-beam radiotherapy (EBRT), vaginal brachytherapy (VBT) or a combination of both, in the management of carcinosarcoma of the uterus is not clearly defined, as only limited randomized trial data are available, indicating a reduction in locoregional recurrences after EBRT. We performed a structured review of data published from 2010. Although no relevant new data from prospective trials or meta-analyses were identified, 14 analyses of cancer registry data from the United States or Europe, focusing predominantly on the endpoint for overall survival, were identified, four of them using propensity-score matching to compare subgroups treated with vs. without radiotherapy. Although stage-by-stage data are rare, the registry analyses support the idea of a beneficial effect, especially of VBT, on overall survival in International Federation of Gynecology and Obstetrics (FIGO) stage IA patients (to a lesser extent in stage IB). For stages II to III, the data sets indicate the largest effects on overall survival for the combination of EBRT and VBT. In all stages, survival effects of radiotherapy apparently persist when given in addition to chemotherapy. Whereas some studies see the strongest survival effects in patients with positive lymph nodes, propensity-score matched data indicate an overall survival effect of radiotherapy (EBRT + VBT or VBT alone) in FIGO stages I to III regardless of lymph node surgery.

Benefit from surgery with additional radiotherapy in N1 head and neck cancer at the time of IMRT: A population-based study on recent developments.

BACKGROUND: Currently, the role of adjuvant irradiation in head and neck cancer (HNC) patients with N1-lymph node status is not clarified. OBJECTIVES: To assess the population-based effect of recent developments in radiotherapy such as intensity-modulated radiotherapy (IMRT) in relation to overall survival (OS) together with surgery in N1 HNC patients. MATERIALS AND METHODS: We used 9,318 HNC cases with pT1/2 N0/1 disease from German cancer registries. Time of diagnosis ranged from January 2000 to December 2014, which we divided into three periods: (low [LIA] vs intermediate [IA] vs high [HIA] IMRT availability period) based on usage of IMRT in Germany. For each period, we examined a possible association between treatment (surgery vs. surgery and radiotherapy) in terms of OS. Statistical analyses included Kaplan-Meier and multivariate Cox regression (models adjusted for HPV-related cancer site). RESULTS: Temporal analysis revealed increasing usage of IMRT in Germany. In patients with N1 tumours, a comparison of patients treated with and without radiotherapy during the HIA period showed a superiority of the combined treatment as opposed to surgery alone (HR 0.54, 95%CI: 0.35-0.85, p = 0.003). The survival analyses related to treatments in terms of period underlined the superiority of surgery plus radiotherapy between periods IA and HIA (p = 0.03). CONCLUSION: The advent of IMRT, additional radiotherapy may present a survival advantage in patients with N1 HNC when combined with surgery.

[Orbital Amyloidosis - Comparison of Two Different Clinical Courses]. / Orbitale Amyloidose ­ Vergleich zweier unterschiedlicher klinischer Verläufe.

BACKGROUND: Primary localised orbital amyloidosis (PLOA) is a very rare disease. In contrast to the isolated manifestation, systemic involvement can be associated with potentially life-threatening consequences. However, the isolated involvement of the orbit can also lead to serious complications. MATERIAL AND METHODS: Two cases of PLOA are described and the necessary ophthalmic, internistic and immunohistochemical diagnostic testing are explained. RESULTS: The first case describes a 71-year-old woman with PLOA. In the clinic, a yellow-orange bumpy prominence in the nasal lower quadrant without further ophthalmological abnormalities was found. Extensive diagnostic testing found no systemic manifestation. The patient herself was free of complaints. In the follow-up over 4 years, patient showed slow progression without ocular complications. The second case is a 72-year-old male patient with similar clinical signs but localisation in the temporal superior quadrant. During the clinical course, multiple ophthalmological complications developed (ptosis, protrusio bulbi, diplopia, secondary glaucoma, perforated corneal ulcer in neurotrophic keratopathy). Perforating keratoplasty had to be performed. Fractioned radiotherapy led to stabilisation of the disease. The follow-up period was 4 years. CONCLUSION: PLOA can lead to visual and organ threatening complications. Accurate diagnosis is required for further diagnostic and therapeutic procedures and to counteract potential local and systemic complications. Interindividual differences in the course have to be considered.

Hyperfractionated accelerated radiation therapy plus cetuximab plus cisplatin chemotherapy in locally advanced inoperable squamous cell carcinoma of the head and neck : Final 5­year results of a phase II study.

BACKGROUND: Cetuximab (CET) is a potent inhibitor of the epidermal growth factor receptor and has been shown to have activity in squamous cell carcinoma of the head and neck (SCCHN). We conducted a single-arm phase II trial of a combination therapy comprising cisplatin (CIS), CET and hyperfractionated accelerated radiotherapy (HART). PATIENTS AND METHODS: Patients with UICC stage III or IVA/B, M0 SCCHN were enrolled and treated with an initial dose of CET (400 mg/m2) and then with a weekly dosage of 250 mg/m2 during HART. HART was started with a prescribed dosage of 2.0 Gy per day for 3 weeks, followed by 1.4 Gy twice daily to a total dose of 70.6 Gy to the gross tumour volume. CIS (40 mg/m2) was administered weekly (days 1, 8, 15, 22, 29 and 36). The primary objective of the phase II study was to determine the 2­year progression-free survival (PFS). RESULTS: Between November 2007 and November 2010, a total of 74 patients were enrolled in the study, of whom 65 were evaluable (83% were men). Median age was 56 years (range 37-69 years). An Oropharyngeal primary tumour was diagnosed in 49%, T4a,b in 65% and N2/3 in 96% of the patients. Of these patients, 85% were smokers or ex-smokers. Complete remission (CR) was observed in 23 patients (35%). The most common toxicity grade was ≥3, including mucositis (58%) and dysphagia (52%). The 2­ and 5­year overall survival rates were 64 and 41%, the 2­ and 5­year PFS rates were 45 and 32%, and the 2­ and 5­year locoregional control rates were 47 and 33%, respectively. CONCLUSION: The combination of weekly CIS with HART plus CET is a feasible regimen for these unfavourable smoking-induced cancers. However, the parallel US study (RTOG 0522) showed no advantage of the enhanced triple therapy compared to chemoradiotherapy alone.

Addition of the Neurokinin-1-Receptor Antagonist (RA) Aprepitant to a 5-Hydroxytryptamine-RA and Dexamethasone in the Prophylaxis of Nausea and Vomiting Due to Radiation Therapy With Concomitant Cisplatin.

PURPOSE: To assess, in a prospective, observational study, the safety and efficacy of the addition of the neurokinin-1-receptor antagonist (NK1-RA) aprepitant to concomitant radiochemotherapy, for the prophylaxis of radiation therapy-induced nausea and vomiting. PATIENTS AND METHODS: This prospective observational study compared the antiemetic efficacy of an NK1-RA (aprepitant), a 5-hydroxytryptamine-RA, and dexamethasone (aprepitant regimen) versus a 5-hydroxytryptamine-RA and dexamethasone (control regimen) in patients receiving concomitant radiochemotherapy with cisplatin at the Department of Radiation Oncology, University Hospital Halle (Saale), Germany. The primary endpoint was complete response in the overall phase, defined as no vomiting and no use of rescue therapy in this period. RESULTS: Fifty-nine patients treated with concomitant radiochemotherapy with cisplatin were included in this study. Thirty-one patients received the aprepitant regimen and 29 the control regimen. The overall complete response rates for cycles 1 and 2 were 75.9% and 64.5% for the aprepitant group and 60.7% and 54.2% for the control group, respectively. Although a 15.2% absolute difference was reached in cycle 1, a statistical significance was not detected (P=.22). Furthermore maximum nausea was 1.58 ± 1.91 in the control group and 0.73 ± 1.79 in the aprepitant group (P=.084); for the head-and-neck subset, 2.23 ± 2.13 in the control group and 0.64 ± 1.77 in the aprepitant group, respectively (P=.03). CONCLUSION: This is the first study of an NK1-RA-containing antiemetic prophylaxis regimen in patients receiving concomitant radiochemotherapy. Although the primary endpoint was not obtained, the absolute difference of 10% in efficacy was reached, which is defined as clinically meaningful for patients by international guidelines groups. Randomized phase 3 studies are necessary to further define the potential role of an NK1-RA in this setting.

Osteogenic differentiation of umbilical cord and adipose derived stem cells onto highly porous 45S5 Bioglass®-based scaffolds.

In the context of bone tissue engineering (BTE), combinations of bioactive scaffolds with living cells are investigated to optimally yield functional bone tissue for implantation purposes. Bioactive glasses are a class of highly bioactive, inorganic materials with broad application potential in BTE strategies. The aim of this study was to evaluate bioactive glass (45S5 Bioglass(®)) samples of composition: 45 SiO2, 24.5 CaO, 24.5 Na2O, and 6 P2O5 (in wt%) as scaffold materials for mesenchymal stem cells (MSC). Pore architecture of the scaffolds as well as cell behavior in the three-dimensional environment was evaluated by several methods. Investigations concerned the osteogenic cell attachment, growth and differentiation of adipose tissue derived MSC (adMSC) compared with MSC from human full term umbilical cord tissues (ucMSC) on porous Bioglass(®)-based scaffolds over a cultivation period of 5 weeks. Differences in lineage-specific osteogenic differentiation of adMSC and ucMSC on Bioglass(®) samples were demonstrated. The investigation led to positive results in terms of cell attachment, proliferation, and differentiation of MSC onto Bioglass(®)-based scaffolds confirming the relevance of these matrices for BTE applications.