Moderate hypofractionated radiotherapy for prostate cancer: 3-year toxicity results of a multicentre randomized phase 3, non-inferiority trial.

BACKGROUND AND PURPOSE: Moderate hypofractionated radiotherapy (HFRT) is a standard treatment for prostate cancer patients. We compared 2 moderate HFRT regimens, with a biologically equivalent dose of 80 Gy in 2 Gy fractions, with a modest simultaneous integrated boost to the dominant intraprostatic lesion. MATERIAL AND METHODS: This is a multicenter, non-inferiority, randomized phase 3 trial with acute toxicity as the primary endpoint, comparing: 56 Gy in 4 weeks (16x3.5 Gy, 4 days/week, Arm A) with 67 Gy in 5 weeks (25x2.68 Gy, 5 days/week, Arm B). The H0 hypothesis is that both regimens are equivalent in terms of acute grade ≥ 2 gastro-intestinal toxicity, defined as a difference in acute grade ≥ 2 gastro-intestinal toxicity of ≤ 10 %. Here we report on acute and late toxicity. RESULTS: We included 170 patients in Arm A and 172 patients in Arm B. The median follow-up time for all patients was 42 months. Acute grade ≥ 2 gastrointestinal toxicity was reported by 24 % of patients in both groups. Acute grade 2 and 3 urinary toxicity was observed in 52 % and 9 % of patients in Arm A and 53 % and 7 % in Arm B. Late grade 2 and grade ≥ 3 gastrointestinal toxicity occurred in 19 % and 4 % of patients in Arm A compared with 15 % and 4 % in Arm B. Late grade 2 and grade ≥ 3 urinary toxicity was observed in 37 % and 10 % of patients in Arm A and 36 % and 6 % in Arm B. CONCLUSION: This analysis confirms that both HFRT regimens are safe and equivalent in terms of acute grade ≥ 2 gastrointestinal toxicity.

Brachytherapy treatment verification using gamma radiation from the internal treatment source combined with an imaging panel-a phantom study.

Brachytherapy has an excellent clinical outcome for different treatment sites. However,in vivotreatment verification is not performed in the majority of hospitals due to the lack of proper monitoring systems. This study investigates the use of an imaging panel (IP) and the photons emitted by a high dose rate (HDR)192Ir source to track source motion and obtain some information related to the patient anatomy. The feasibility of this approach was studied by monitoring the treatment delivery to a 3D printed phantom that mimicks a prostate patient. A 3D printed phantom was designed with a template for needle insertion, a cavity ('rectum') to insert an ultrasound probe, and lateral cavities used to place tissue-equivalent materials. CT images were acquired to create HDR192Ir treatment plans with a range of dwell times, interdwell distances and needle arrangements. Treatment delivery was verified with an IP placed at several positions around the phantom using radiopaque markers on the outer surface to register acquired IP images with the planning CT. All dwell positions were identified using acquisition times ≤0.11 s (frame rates ≥ 9 fps). Interdwell distances and dwell positions (in relation to the IP) were verified with accuracy better than 0.1 cm. Radiopaque markers were visible in the acquired images and could be used for registration with CT images. Uncertainties for image registration (IP and planning CT) between 0.1 and 0.4 cm. The IP is sensitive to tissue-mimicking insert composition and showed phantom boundaries that could be used to improve treatment verification. The IP provided sufficient time and spatial resolution for real-time source tracking and allows for the registration of the planning CT and IP images. The results obtained in this study indicate that several treatment errors could be detected including swapped catheters, incorrect dwell times and dwell positions.

Automatic Quality Assessment of Transperineal Ultrasound Images of the Male Pelvic Region, Using Deep Learning.

Ultrasound guidance is not in widespread use in prostate cancer radiotherapy workflows. This can be partially attributed to the need for image interpretation by a trained operator during ultrasound image acquisition. In this work, a one-class regressor, based on DenseNet and Gaussian processes, was implemented to automatically assess the quality of transperineal ultrasound images of the male pelvic region. The implemented deep learning approach was tested on 300 transperineal ultrasound images and it achieved a scoring accuracy of 94%, a specificity of 95% and a sensitivity of 92% with respect to the majority vote of 3 experts, which was comparable with the results of these experts. This is the first step toward a fully automatic workflow, which could potentially remove the need for ultrasound image interpretation and make real-time volumetric organ tracking in the radiotherapy environment using ultrasound more appealing.

Decision Support Systems in Prostate Cancer Treatment: An Overview.

BACKGROUND: A multifactorial decision support system (mDSS) is a tool designed to improve the clinical decision-making process, while using clinical inputs for an individual patient to generate case-specific advice. The study provides an overview of the literature to analyze current available mDSS focused on prostate cancer (PCa), in order to better understand the availability of decision support tools as well as where the current literature is lacking. METHODS: We performed a MEDLINE literature search in July 2018. We divided the included studies into different sections: diagnostic, which aids in detection or staging of PCa; treatment, supporting the decision between treatment modalities; and patient, which focusses on informing the patient. We manually screened and excluded studies that did not contain an mDSS concerning prostate cancer and study proposals. RESULTS: Our search resulted in twelve diagnostic mDSS; six treatment mDSS; two patient mDSS; and eight papers that could improve mDSS. CONCLUSIONS: Diagnosis mDSS is well represented in the literature as well as treatment mDSS considering external-beam radiotherapy; however, there is a lack of mDSS for other treatment modalities. The development of patient decision aids is a new field of research, and few successes have been made for PCa patients. These tools can improve personalized medicine but need to overcome a number of difficulties to be successful and require more research.

A randomised controlled trial of intravenous dexamethasone combined with interscalene brachial plexus blockade for shoulder surgery.

We recruited patients scheduled for shoulder rotator cuff repair or subacromial decompression under general anaesthesia and interscalene brachial plexus blockade (30 ml ropivacaine 0.5%). We allocated 240 participants into four groups of 60 that were given pre-operative saline 0.9% or dexamethasone 1.25 mg, 2.5 mg or 10 mg, intravenously. We recorded outcomes for 48 h. The median (IQR [range]) time to first postoperative analgesic request after saline was 12.2 (11.0-14.1 [1.8-48]) h, which was extended by intravenous dexamethasone 2.5 mg and 10 mg to 17.4 (14.9-21.5 [7.2-48]) h, p < 0.0001, and 20.1 (17.2-24.3 [1.3-48]) h, p < 0.0001, respectively, but not by dexamethasone 1.25 mg, 14.0 (12.1-17.7 [2.1-48]) h, p = 0.05. Postoperative analgesia was given sooner after rotator cuff repair than subacromial decompression, hazard ratio (95% CI) 2.2 (1.6-3.0), p < 0.0001, but later in older participants, hazard ratio (95% CI) 0.98 (0.97-0.99) per year, p < 0.0001.

Can metformin improve 'the tomorrow' of patients treated for oesophageal cancer?

INTRODUCTION: Recent studies suggest that the use of metformin is associated with reduced cancer incidence and improved prognosis in patients with oesophageal cancer. We explored the relationship between the use of metformin and outcome (pathologic response rate, distant metastasis-free and overall survival) in our mono-institutional cohort of patients treated for oesophageal cancer. MATERIAL AND METHODS: Between 2008 and 2014, a total of 196 patients with oesophageal cancer (ages ranged from 37 to 82 years) eligible for curative treatment entered the study. Patients were categorized as non-diabetic (n = 172), diabetic not taking metformin (n = 5) or diabetic taking metformin (n = 19). The majority of patients were treated with trimodality therapy (n = 189). Pathologic response was graded according to Mandard's tumour regression score at the time of surgery. Distant metastasis-free and overall survival were calculated using the Kaplan-Meier method with log rank comparisons performed to determine significance. RESULTS: The overall pathologic complete response rate for the study population was 26%. It was 25% for patients not using metformin and 39% for diabetics taking metformin (p = 0.260). The two-year overall survival rate for the whole group was 59%. Use of metformin was associated with a significantly better distant metastasis-free survival rate (p = 0.040) or overall survival rate (p = 0.012). Multivariate analysis using Cox regression found that metformin treatment significantly prolonged survival (p = 0.043). CONCLUSION: In our population-based study, the use of metformin was associated with an improved overall and distant metastasis-free survival rate in patients with oesophageal cancer. These data are complementary to one other clinical study and warrant further prospective study.

Image-guided stereotactic ablative radiotherapy for the liver: a safe and effective treatment.

AIMS: Stereotactic ablative body radiotherapy (SABR) is a non-invasive treatment option for inoperable patients or patients with irresectable liver tumors. Outcome and toxicity were evaluated retrospectively in this single-institution patient cohort. PATIENTS AND METHODS: Between 2010 and 2014, 39 lesions were irradiated in 33 consecutive patients (18 male, 15 female, median age of 68 years). All the lesions were liver metastases (n = 34) or primary hepatocellular carcinomas (n = 5). The patients had undergone four-dimensional respiration-correlated PET-CT for treatment simulation to capture tumor motion. We analyzed local control with a focus on CT-based response at three months, one year and two years after treatment, looking at overall survival and the progression pattern. RESULTS: All patients were treated with hypofractionated image-guided stereotactic radiotherapy. The equivalent dose in 2 Gy fractions varied from 62.5 Gy to 150 Gy, delivered in 3-10 fractions (median dose 93.8 Gy, alpha/beta = 10). The CT-based regression pattern three months after radiotherapy revealed partial regression in 72.7% of patients with a complete remission in 27.3% of the cases. The site of first progression was predominantly distant. One- and two-year overall survival rates were 85.4% and 68.8%, respectively. No toxicity of grade 2 or higher according to the NCI Common Terminology Criteria for Adverse Events v4.0 was observed. CONCLUSION: SABR is a safe and efficient treatment for selected inoperable patients or irresectable tumors of the liver. Future studies should combine SABR with systemic treatment acting in synergy with radiation, such as immunological interventions or hypoxic cell radiosensitizers to prevent distant relapse.

Involved field radiotherapy for locally advanced non-small cell lung cancer: isolated mediastinal nodal relapse.

The current standard of care for locally advanced inoperable non-small cell lung cancer is high dose radiotherapy with concurrent chemotherapy. We report on a patient with stage IIIA NSCLC treated with concurrent chemoradiotherapy on the primary tumor and the 18-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) positive hilar and mediastinal lymph nodes. Six months after treatment this patient developed a single isolated contralateral mediastinal nodal relapse outside but in the proximity of the irradiated target volume. This patient was successfully re-irradiated to this isolated nodal relapse after reconstruction of the dose given to the localisation of this regional recurrence. This case describes the clinical problem of a regional recurrence after involved field radiotherapy that occasionally occurs. A possible explanation for those regional recurrences is an under staging of extension of the disease because the time-interval between the staging (18)FDG-PET-CT scan and the start of the irradiation was too long. If the time-interval is 4 weeks or more, we strongly recommend a new (18)FDG-PET-CT because of the possibility of upstaging of the disease.

Determination of methylmercury in environmental samples using static headspace gas chromatography and atomic fluorescence detection after aqueous phase ethylation.

A rapid and automated method for the determination of monomethylmercury (MMHg) in environmental samples was developed using headspace gas chromatography with atomic fluorescence detection in combination with aqueous phase ethylation. Sample preparation steps were optimized for sediments, biological samples, and water samples using certified reference materials and real samples with a broad range of MMHg concentrations. Different extraction procedures were compared for both sediments and biological samples. The methods were applied in the intercomparison exercises for the certification of MMHg in sediments (IAEA 405) and in Oyster tissue (BCR 710) and the results were accepted for certification. The detection limits for MMHg are 0.002 ng Hg/g for sediments and biological samples and 0.01 ng Hg/L for water samples. The method was tested for methylation artifacts; no artifact was observed in the sediment samples and CRMs tested.

[Herpes gestationis. A histological and electron microscopic study (author's transl)]. / Herpes gestationis. Etude histologique et ultrastructurale.

The histology and electron microscopy of two cases of herpes gestationis is described (HG). It appears that at the histological as well as at the ultrastructural level, the blister of HG results from degenerative changes in the basal cells and is initially located in the epidermis. It is associated with spongiosis. As a consequence of the disappearance of the basal cell layer, the blister is secondarily found between the malpighian layer and the subepidermal basement membrane. Immunologically, C3 could be found at that dermo-epidermal junction. Although the immunological findings can be similar to those of BP, it is believed that HG and BP must be considered as different entities, because of the very particular clinical features of HG and because the blister formation is different in both diseases.