Paul Martin Putora

Comorbidities and Burden of COPD: A Population Based Case-Control Study

COPD is associated with a relevant burden of disease and a high mortality worldwide. Only recently, the importance of comorbidities of COPD has been recognized. Studies postulated an association with inflammatory conditions potentially sharing pathogenic pathways and worsening overall prognosis. More evidence is required to estimate the role of comorbidities of COPD. Our aim was to investigate the prevalence and clustering of comorbidities associated with COPD, and to estimate their impact on clinically relevant outcomes. In this population-based case-control study, a nation-wide database provided by the Swiss Federal Office for Statistics enclosing every hospital entry covering the years 2002–2010 (n = 12′888′075) was analyzed using MySQL and R statistical software. Statistical methods included non-parametric hypothesis testing by means of Fisher’s exact test and Wilcoxon rank sum test, as well as linear models with generalized estimating equation to account for intra-patient variability. Exploratory multivariate approaches were also used for the identification of clusters of comorbidities in COPD patients. In 2.6% (6.3% in patients aged >70 years) of all hospitalization cases an active diagnosis of COPD was recorded. In 21% of these cases, COPD was the main reason for hospitalization. Patients with a diagnosis of COPD had more comorbidities (7 [IQR 4–9] vs. 3 [IQR 1–6]; ), were more frequently rehospitalized (annual hospitalization rate 0.33 [IQR 0.20–0.67] vs. 0.25 [IQR 0.14–0.43]/year; ), had a longer hospital stay (9 [IQR 4–15] vs. 5 [IQR 2–11] days; ), and had higher in-hospital mortality (5.9% [95% CI 5.8%–5.9%] vs. 3.4% [95% CI 3.3%–3.5%]; ) compared to matched controls. A set of comorbidities was associated with worse outcome. We could identify COPD-related clusters of COPD-comorbidities.

Relevance of Incidental Colorectal FDG-PET/CT-Enhanced Lesions

Introduction: Positron emission tomography/computed tomographies (PET/CTs) may result in incidental findings of fluorodeoxyglucose (FDG)-avid lesions in the colon. The aim of this study was to assess the relevance of a colonoscopic workup of such lesions. Patients and Methods: We retrospectively analysed all PET/CT reports (n = 4,973) generated in our nuclear medicine department between May 2006 and May 2011; in 69 cases a colonoscopic evaluation was recommended for incidental FDG-avid lesions. Results: Of these 69 cases, 51 underwent colonoscopy because of the potential need for further treatment. The maximum standardized uptake values (SUVmax) ranged from 5.0 to 42.0 with an average of 10.9. In 44 of the 51 patients, a histopathological abnormality was found on colonoscopy, 44 in the location described by PET/CT. A further 38 lesions were identified that were not visible on PET/CT. The histopathological evaluation in the 51 patients revealed 14 hyperplastic polyps, 27 adenomas with low-grade and 4 with high-grade dysplasia, 3 adenocarcinomas and 1 neuro-endocrine tumour. Conclusion: Incidental findings of focal colorectal FDG uptake should lead to further workup with colonoscopy. The SUVmax was not predictive for higher grade histologies. With an SUV of 5 the yield was high for colonic premalignant and malignant lesions. However, malignancy cannot be ruled out in focal lesions with an SUV of less than 5, and for individual patients a colonoscopy should not be ruled out.

Guidance of treatment decisions in risk-adapted primary radiotherapy for prostate cancer using multiparametric magnetic resonance imaging: a single center experience

BackgroundMagnetic resonance imaging (MRI) of the prostate is considered to be the most precise noninvasive staging modality for localized prostate cancer. Multiparametric MRI (mpMRI) dynamic sequences have recently been shown to further increase the accuracy of staging relative to morphological imaging alone. Correct radiological staging, particularly the detection of extraprostatic disease extension, is of paramount importance for target volume definition and dose prescription in highly-conformal curative radiotherapy (RT); in addition, it may affect the risk-adapted duration of additional antihormonal therapy. The purpose of our study was to analyze the impact of mpMRI-based tumor staging in patients undergoing primary RT for prostate cancer.MethodsA total of 122 patients admitted for primary RT for prostate cancer were retrospectively analyzed regarding initial clinical and computed tomography-based staging in comparison with mpMRI staging. Both tumor stage shifts and overall risk group shifts, including prostate-specific antigen (PSA) level and the Gleason score, were assessed. Potential risk factors for upstaging were tested in a multivariate analysis. Finally, the impact of mpMRI-based staging shift on prostate RT and antihormonal therapy was evaluated.ResultsOverall, tumor stage shift occurred in 55.7% of patients after mpMRI. Upstaging was most prominent in patients showing high-risk serum PSA levels (73%), but was also substantial in patients presenting with low-risk PSA levels (50%) and low-risk Gleason scores (45.2%). Risk group changes occurred in 28.7% of the patients with consequent treatment adaptations regarding target volume delineation and duration of androgen deprivation therapy. High PSA levels were found to be a significant risk factor for tumor upstaging and newly diagnosed seminal vesicle infiltration assessed using mpMRI.ConclusionsOur findings suggest that mpMRI of the prostate leads to substantial tumor upstaging, and can considerably affect treatment decisions in all patient groups undergoing risk-adapted curative RT for prostate cancer.

Swarm-Based Medicine

Occasionally, medical decisions have to be taken in the absence of evidence-based guidelines. Other sources can be drawn upon to fill in the gaps, including experience and intuition. Authorities or experts, with their knowledge and experience, may provide further input—known as “eminence-based medicine”. Due to the Internet and digital media, interactions among physicians now take place at a higher rate than ever before. With the rising number of interconnected individuals and their communication capabilities, the medical community is obtaining the properties of a swarm. The way individual physicians act depends on other physicians; medical societies act based on their members. Swarm behavior might facilitate the generation and distribution of knowledge as an unconscious process. As such, “swarm-based medicine” may add a further source of information to the classical approaches of evidence- and eminence-based medicine. How to integrate swarm-based medicine into practice is left to the individual physician, but even this decision will be influenced by the swarm.

Objective consensus from decision trees

BackgroundConsensus-based approaches provide an alternative to evidence-based decision making, especially in situations where high-level evidence is limited. Our aim was to demonstrate a novel source of information, objective consensus based on recommendations in decision tree format from multiple sources.MethodsBased on nine sample recommendations in decision tree format a representative analysis was performed. The most common (mode) recommendations for each eventuality (each permutation of parameters) were determined. The same procedure was applied to real clinical recommendations for primary radiotherapy for prostate cancer. Data was collected from 16 radiation oncology centres, converted into decision tree format and analyzed in order to determine the objective consensus.ResultsBased on information from multiple sources in decision tree format, treatment recommendations can be assessed for every parameter combination. An objective consensus can be determined by means of mode recommendations without compromise or confrontation among the parties. In the clinical example involving prostate cancer therapy, three parameters were used with two cut-off values each (Gleason score, PSA, T-stage) resulting in a total of 27 possible combinations per decision tree. Despite significant variations among the recommendations, a mode recommendation could be found for specific combinations of parameters.ConclusionRecommendations represented as decision trees can serve as a basis for objective consensus among multiple parties.

FDG‐PET SUV‐max values do not correlate with epidermal growth factor receptor mutation status in lung adenocarcinoma

Previous reports suggest a correlation between positron emission tomography with fluorodeoxyglucose maximum standardized uptake value (SUVmax) and epidermal growth factor receptor (EGFR) mutation status in lung cancer. We analysed positron emission tomography with fluorodeoxyglucose SUVmax in 14 patients with EGFR mutations, and a control group of 14 subjects with wild‐type EGFR adenocarcinomas. The mean SUV value was 10.7 for EGFR‐mutated adenocarcinomas and 9.9 for wild‐type tumours. There was no correlation between SUV values and EGFR mutation status. Omitting EGFR testing in lung cancers with low SUVmax is not appropriate.

Oesophageal cancer: Exploring controversies overview of experts' opinions of Austria, Germany, France, Netherlands and Switzerland

BackgroundOesophageal carcinoma is a rare disease with often dismal prognosis. Despite multiple trials addressing specific issues, currently, many questions in management remain unanswered. This work aimed to specifically address areas in the management of oesophageal cancer where high level evidence is not available, performing trials is very demanding and for many questions high-level evidence will not be available in the forseeable future.MethodsTwo experts of each national, oesophageal cancer research group from Austria, France, Germany, the Netherlands and Switzerland were asked to provide statements to controversial issues. After an initial survey, further questions were formulated and answered by all experts. The answers were then discussed and qualitatively analysed for consensus and controversy.ResultsTopics such as indications for PET-CT, reasons for induction chemotherapy, radiotherapy dose, the choice of definitive chemo-radiotherapy versus surgery in squamous cell cancer, the role of radiotherapy in adenocarcinoma and selected surgical issues were identified as topics of interest and discussed.ConclusionAreas of significant controversy exist in the management of oesophageal cancer, mostly due to high-level evidence. This is not expected to change in the upcoming years.

Thoracic oncology HERMES: European curriculum recommendations for training in thoracic oncology

The HERMES (Harmonising Education in Respiratory Medicine for European Specialists) project is funded by the European Respiratory Society (ERS) and has the declared aims of harmonising education in thoracic medicine, recognising diplomas and certificates of qualification, and improving free access and mobility for medical specialists across the European Union (EU). This takes into account Directive 2013/55/EU of the European Parliament and of the Council [1] on the recognition of professional qualifications, one of the pillars of EU legislation. Moreover, it conforms to the fact that there is a shortage of medical/surgical specialists in several European countries, which means that more physicians of other European and non-European countries will be needed to sustain the functioning and development of health services in future years and decades [2]. HERMES is working towards the development of harmonised and structured programmes for education across respiratory specialties to ensure that the best care is delivered for those suffering from respiratory diseases. Thoracic oncology HERMES: European curriculum recommendations for training in thoracic oncology http://ow.ly/mdqT300NHqO

Second-line treatment for metastatic clear cell renal cell cancer: experts’ consensus algorithms

BackgroundSecond-line systemic treatment options for metastatic clear cell renal cell cancer (mccRCC) are diverse and treatment strategies are variable among experts. Our aim was to investigate the approach for the second-line treatment after first-line therapy with a tyrosine kinase inhibitor (TKI). Recently two phase III trials have demonstrated a potential role for nivolumab (NIV) and cabozantinib (CAB) in this setting. We aimed to estimate the impact of these trials on clinical decision making.Materials and methodsEleven international experts were asked to provide their treatment strategies for second-line systemic therapy for mccRCC in the current setting and once NIV and CAB will be approved and available. The treatment strategies were analyzed with the objective consensus approach.ResultsThe analysis of the decision trees revealed everolimus (EVE), axitinib (AXI), NIV and TKI switch (sTKI) as therapeutic options after first-line TKI therapy in the current situation and mostly NIV and CAB in the future setting. The most commonly used criteria for treatment decisions were duration of response, TKI tolerance and zugzwang a composite of several related criteria.ConclusionIn contrast to the first-line setting, recommendations for second-line systemic treatment of mccRCC among experts were not as heterogeneous. The agents mostly used after disease progression on a first-line TKI included: EVE, AXI, NIV and sTKI. In the future setting of NIV and CAB availability, NIV was the most commonly chosen drug, whereas several experts identified situations where CAB would be preferred.

Erectile function following brachytherapy, external beam radiotherapy, or radical prostatectomy in prostate cancer patients

Background and purposeFor localized prostate cancer, treatment options include external beam radiotherapy (EBRT), radical prostatectomy (RP), and brachytherapy (BT). Erectile dysfunction (ED) is a common side-effect. Our aim was to evaluate penile erectile function (EF) before and after BT, EBRT, or RP using a validated self-administered quality-of-life survey from a prospective registry.Material and methodsAnalysis included 478 patients undergoing RP (n = 252), EBRT (n = 91), and BT (n = 135) with at least 1 year of follow-up and EF documented using IIEF-5 scores at baseline, 6 weeks, 6 months, 1 year, and annually thereafter.ResultsDifferences among treatments were most pronounced among patients with no or mild initial ED (IIEF-5 ≥ 17). Overall, corrected for baseline EF and age, BT was associated with higher IIEF-5 scores than RP (+ 7.8 IIEF-5 score) or EBRT (+ 3.1 IIEF-5 score). EBRT was associated with better IIEF-5 scores than RP (+ 4.7 IIEF-5 score). In patients undergoing EBRT or RP with bilateral nerve sparing (NS), recovery of EF was observed and during follow-up, the differences to BT were not statistically significant. Overall age had a negative impact on EF preservation (corrected for baseline IIEF).ConclusionIn our series, EF was adversely affected by each treatment modality. Considered overall, BT provided the best EF preservation in comparison to EBRT or RP.ZusammenfassungHintergrund und ZielDie externe Radiotherapie (EBRT), die radikale Prostatektomie (RP) sowie die Brachytherapie (BT) stellen Behandlungsoptionen für das lokalisierte Prostatakarzinom dar. Die erektile Dysfunktion (ED) ist eine häufige Nebenwirkung dieser Therapien. Unser Ziel war es, die penile erektile Funktion (EF) vor und nach BT, EBRT und RP mit Hilfe eines validierten, vom Patienten ausgefüllten Lebensqualitätsfragebogens aus einer prospektiven Datenbank zu beurteilen.Material und MethodenMit einer minimalen Nachbeobachtungszeit von einem Jahr wurden 478 Patienten analysiert, die eine RP (n = 252), EBRT (n = 91) oder BT (n = 135) erhalten hatten und deren EF mit dem IIEF-5-Score vor Therapie sowie nach 6 Wochen, 6 Monaten, nach einem Jahr und danach jährlich ermittelt worden sind.ErgebnisDie größten therapiebedingten Unterschiede wurden bei Patienten ohne oder nur mit milder initialer ED beobachtet (IIEF-5 ≥ 17). Korrigiert für die EF und das Alter bei Therapie, war die BT mit höherem IIEF-5-Score assoziiert als die RP (+ 7,8 IIEF-5-Score) oder die EBRT (+ 3,1 IIEF-5-Score). Die EBRT war mit einem besseren IIEF-5-Score assoziiert als die RP (+ 4,7 IIEF-5-Score). Bei Patienten mit bilateraler nervenschonender RP oder einer EBRT wurde eine Erholung der EF beobachtet; im Verlauf war der Unterschied zur BT nicht mehr statistisch signifikant. Insgesamt hatte ein höheres Alter einen negativen Einfluss auf die Erhaltung der EF (korrigiert für Ausgangs-EF).SchlussfolgerungIn unserer Serie verschlechterte sich die EF durch alle Therapieformen. Insgesamt bot die BT die beste EF-Erhaltung verglichen mit der EBRT oder RP.