Radiation-associated sarcoma after breast cancer in a nationwide population : Increasing risk of angiosarcoma

Radiation-associated sarcoma (RAS) is a rare complication of radiation therapy (RT) to breast cancer (BC). This study explored RAS after RT to BC in a nationwide population-based material. The Finnish Cancer Registry was queried for patients with BC treated during 1953-2014 who were later diagnosed with a secondary sarcoma in 1953-2014. Registry data, patient files, and sarcoma specimens were analyzed to confirm diagnosis and location of RAS at or close to the RT target volume. A total of 132 512 patients were diagnosed with invasive BC during the study period. A subsequent sarcoma was diagnosed in 355 patients. After exclusion, 96 RAS were identified. Angiosarcoma (AS) was the most prevalent histology in 50 (52%) of 96 patients. However, the first radiation-associated AS was diagnosed in a patient treated for BC with breast-conserving surgery in 1984, and thereafter, the proportion of AS continuously increased. The 5-year sarcoma-specific survival was 75.1% for RAS treated with a curative intent. The distribution of histologic subtypes of RAS has changed during the 60 years of this registry study. The first radiation-associated AS was diagnosed in 1989, and presently, AS is the most common histologic subtype of RAS. It is possible that changes in BC treatment strategies are influencing the characteristics of RAS.Peer reviewe

Improved prognosis in soft-tissue sarcoma of extremity and trunk wall : Comparison of patients diagnosed during 1998-2001 and 2005-2010 in Finland

Background and purpose - Soft-tissue sarcoma (STS) is rare, with challenging individualized treatment, so diagnostics and treatment should be centralized. Historical controls are sometimes used for investigation of whether new diagnostic or therapeutic tools affect patient outcome. However, as yet unknown factors may affect the outcome. We investigated prognostic factors and prognosis in 2 nationwide cohorts of patients diagnosed with a local STS during the periods 1998-2001 and 2005-2010, with special interest in finding factors lying behind possible improvement of prognosis. Patients and methods - 2 cohorts of patients with STS of the extremities or trunk diagnosed during the periods 1998-2001 and 2005-2010 were retrieved from the nationwide Finnish Cancer Registry. Detailed information was gathered from patient files. Results - Compared to first cohort, a larger proportion of patients with inadequate surgery in the second cohort received radiation therapy, and both the local control rate and the sarcoma-specific survival rate improved in the second cohort. For sarcoma-specific survival, cohort (HR =0.6, 95% CI: 0.5-0.9), age, depth, grade, and margin were significant factors in multivariate analysis. For local control, cohort (HR =0.6, 95% CI: 0.5-0.9), age, and margin were significant in multivariate analysis. Interpretation - Known prognostic factors including type of treatment did not entirely explain the secular trend of continuous improvement in prognosis in STS. This illustrates the danger of using historical controls for investigation of whether new diagnostic or therapeutic tools have an effect on patient outcome.Peer reviewe

Treatment and Prognosis of Radiation-Associated Breast Angiosarcoma in a Nationwide Population

Background Radiation-associated angiosarcoma of the breast (RAASB) is an aggressive malignancy that is increasing in incidence. Only a few previous population-based studies have reported the results of RAASB treatment. Methods A search for RAASB patients was carried out in the Finnish Cancer Registry, and treatment data were collected to identify prognostic factors for survival. Results Overall, 50 RAASB patients were identified. The median follow-up time was 5.4 years (range 0.4-15.6), and the 5-year overall survival rate was 69%. Forty-seven (94%) patients were operated on with curative intent. Among these patients, the 5-year local recurrence-free survival, distant recurrence-free survival, and overall survival rates were 62%, 75%, and 74%, respectively. A larger planned surgical margin was associated with improved survival. Conclusions We found that the majority of RAASB patients were eligible for radical surgical management in this population-based analysis. With radical surgery, the prognosis is relatively good.Peer reviewe

Local relapse of soft tissue sarcoma of the extremities or trunk wall operated on with wide margins without radiation therapy

Background: The quality of surgical margins is the most important factor affecting local control in soft tissue sarcoma (STS). Despite this, there is no universally accepted consensus on the definition of an adequate surgical margin or on which patients should be offered radiation therapy. This study focuses on local control and its prognostic factors in patients with trunk wall and extremity STS. Methods: Adult patients with a final diagnosis of trunk wall or extremity STS referred to a single tertiary referral centre between August 1987 and December 2016 were identified from a prospective institutional database. Patients were treated according to a protocol instituted in 1987. The classification of surgical margins and indications for radiation therapy were based on anatomy and strict definition of surgical margins as metric distance to the resection border. Local treatment was defined as adequate if patients received either surgery with wide margins alone or marginal surgery combined with radiation therapy. Margins were considered wide if the tumour was excised with pathological margins greater than 2.5 cm or with an uninvolved natural anatomical barrier. After treatment, patients were followed up with local imaging and chest X-ray: 5 years for high-grade STS, 10 years for low-grade STS. Results: A total of 812 patients were included with a median follow-up of 5.8 (range 0.5-19.5) years. Forty-four patients had a grade 1 tumour: there were no instances of recurrence in this group thus they were excluded from further analysis. Five-year local control in the 768 patients with grade 2-3 STS was 90.1 per cent in patients receiving adequate local treatment according to the protocol. Altogether, 333 patients (43.4 per cent) were treated with wide surgery alone and their 5-year local control rate was 91.1 per cent. Among patients treated with wide surgery alone, deep location was the only factor adversely associated with local relapse risk in multivariable analysis; 5-year local control was 95.3 per cent in superficial and 88.3 per cent in deep-sited sarcomas (hazards ratio 3.154 (95% c.i. 1.265 to 7.860), P = 0.014). Conclusion: A high local control rate is achievable with surgery alone for a substantial proportion of patients with STS of the extremities or superficial trunk wall.Peer reviewe

Visual Counting and Automated Image-analytic Assessment of Ki-67 and their Prognostic Value in Synovial Sarcoma

BACKGROUND: Ki-67 is a widely used proliferation marker reflecting prognosis in various tumors. However, visual assessment and scoring of Ki-67 suffers from marked inter-observer and intra-observer variability. We aimed to assess the concordance of manual counting and automated image-analytic scoring methods for Ki-67 in synovial sarcoma. PATIENTS AND METHODS: Tissue microarrays from 34 patients with synovial sarcoma were immunostained for Ki-67 and scored both visually and with 3DHistech QuantCenter. RESULTS: The automated assessment of Ki-67 expression was in good agreement with the visually counted Ki-67 (r Pearson =0.96, p<0.001). In a Cox regression model automated [hazard ratio (HR)=1.047, p=0.024], but not visual (HR=1.063, p=0.053) assessment method associated high Ki-67 scores with worse overall survival. CONCLUSION: The automated Ki-67 assessment method appears to be comparable to the visual method in synovial sarcoma and had a significant association to overall survival.publishedVersionPeer reviewe

Validity of five foot and ankle specific electronic patient-reported outcome (ePRO) instruments in patients undergoing elective orthopedic foot or ankle surgery

Background: Patient-reported outcomes (PROS) are widely accepted measures for evaluating outcomes of surgical interventions. As patient-reported information is stored in electronic health records, it is essential that there are valid electronic PRO (ePRO) instruments available for clinicians and researchers. The aim of this study was to evaluate the validity of electronic versions of five widely used foot and ankle specific PRO instruments. Methods: Altogether 111 consecutive elective foot/ankle surgery patients were invited face-to-face to participate in this study. Patients completed electronic versions of the Foot and Ankle Ability Measure (FAAM), the Foot and Ankle Outcome Score (FAOS), the modified Lower Extremity Function Scale (LEFS), the Manchester-Oxford Foot Questionnaire (MOXFQ), and the Visual Analogue Scale Foot and Ankle (VAS-FA) on the day of elective foot and/or ankle surgery. Construct validity, coverage, and targeting of the scales were assessed. Results: Based on general and predefined thresholds, construct validity, coverage, and targeting of the ePRO versions of the FAAM, the FAOS, the MOXFQ, and the VAS-FA were acceptable. Major issues arose with score distribution and convergent validity of the modified LEFS instrument. Conclusions: The ePRO versions of the FAAM, the FAOS, the MOXFQ and the VAS-FA provide valid scores for foot and ankle patients. However, our findings do not support the use of the modified LEFS as an electronic outcome measure for patients with orthopedic foot and/or ankle pathologies. (C) 2020 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr