Short fractionation radiotherapy for early prostate cancer in the time of COVID-19: long-term excellent outcomes from a multicenter Italian trial suggest a larger adoption in clinical practice

Abstract Introduction: To evaluate stereotactic body radiotherapy (SBRT) in low-risk Prostate Cancer patients as preferred treatment option in emergency health conditions. Materials and methods: From April 2013 to September 2015, 28 patients with low-risk prostate cancer were prospectively enrolled. The SBRT prescribed dose was 36.25 Gy in 5 fractions, twice a week. Primary endpoints were acute and late toxicity. Secondary endpoints were biochemical recurrence free survival (bRFS) and overall survival. Results: Median follow-up was 65.5 months (range 52-81). No acute G3 or G4 toxicity was recorded. Acute G1 or G2 genitourinary (GU) toxicity occurred in 43% and acute G1-G2 gastrointestinal (GI) toxicity in 14%. Late G1 and G3 GU toxicity in 18% and 3.5%, respectively. The G3 toxicity was not directly attributable to radiotherapy. Late G1 GI toxicity occurred in 18%. 5yy bRFS was 96.5% (95% CI 82.3-99.4%). Conclusions: Stereotactic body radiotherapy for early prostate cancer reported safe toxicity profile and a good clinical outcome at the median follow-up of 5 years. It may be an useful option if radiotherapy is required in emergency medical conditions

Accuracy and limitations of the growth hormone (GH) releasing hormone-arginine retesting in young adults with childhood-onset GH deficiency

Background: Re-testing for GH secretion is needed to confirm the diagnosis of GH deficiency (GHD) after adult height achievement in childhood-onset GHD (COGHD). Aim: To define the cut-off of GH peak after retesting with GH-releasing hormone plus arginine (GHRHarg) in the diagnosis of permanent GHD in COGHD of different etiology. Patients and methods: Eighty-eight COGHD (median age 17.2 y), 29 idiopathic GHD (IGHD), 44 cancer survivors (TGHD) and 15 congenital GHD (CGHD) were enrolled in the study; 54 had isolated GHD (iGHD) and 34 had multiple pituitary hormone deficiencies (MPHD). All were tested with insulin tolerance test (ITT) and GHRHarg. IGHD with a GH response to ITT 656\ub5g/L were considered true negatives and served as the control group, and patients with a GH response <6\ub5g/L as true positives. Baseline IGF-I was also measured. The diagnostic accuracy of GHRHarg testing and of IGF-I SDS in patients with GHD of different etiologies was evaluated by ROC analysis. Results: Forty-six subjects with a GH peak to ITT 656\ub5g/L and 42 with GH peak <6 \ub5g/L showed a GH peak after GHRHarg between 8.8\u2013124\ub5g/L and 0.3\u201326.3\ub5g/L, respectively; 29 IGHD were true negatives, 42 were true positives and 17 with a high likelihood GHD showed a GH peak to ITT 656\ub5g/L. ROC analysis based on the etiology indicated the best diagnostic accuracy for peak GH cutoffs after GHRHarg of 25.3 \ub5g/L in CGHD, 15.7 in TGHD, and 13.8 in MPHD, and for IGF-1 SDS at 122.1 in CGHD, 121.5 in TGHD, and 121.9 in MPHD. Conclusions: Our findings indicate that the best cut-off for GH peak after retesting with GHRHarg changes according to the etiology of GHD during the transition age. Based on these results the diagnostic accuracy of GHRHarg remains questionable

Quality of life changes over time and predictors in a large head and neck patients’ cohort: secondary analysis from an Italian multi-center longitudinal, prospective, observational study—a study of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) head and neck working group

Purpose: The present study examined the longitudinal trajectories, through hierarchical modeling, of quality of life among patients with head and neck cancer, specifically symptoms burden, during radiotherapy, and in the follow-up period (1, 3, 6, and 12 months after completion of radiotherapy), through the M.D. Anderson Symptom Inventory Head and Neck questionnaire, formed by three factors. Furthermore, analyses were conducted controlling for socio-demographic as well as clinical characteristics. Methods: Multi-level mixed-effects linear regression was used to estimate the association between quality of life and time, age, gender, household, educational level, employment status, ECOG performance status, human papilloma virus (HPV) status, surgery, chemotherapy, alcohol intake, and smoking. Results: Among the 166 participants, time resulted to be a predictor of all the three questionnaire factors, namely, general and specific related symptoms and interference with daily life. Moreover, regarding symptom interference with daily activities factor, HPV-positive status played a significant role. Considering only HPV-negative patients, only time predicted patients' quality of life. Differently, among HPV-positive patients, other variables, such as gender, educational level, alcohol use, surgery, age at diagnosis, employment status, and ECOG status, resulted significant. Conclusion: It was evident that quality of life of patients with head and neck cancer declined during RT, whereas it slowly improved after ending treatment. Our results clarified the role of some socio-demographic and clinical variables, for instance, HPV, which would allow to develop treatments tailored to each patient

Measurement of stress waves in polymers generated by UV laser ablation

Propagation of stress waves into polymer substrates undergoing UV laser ablation has been studied by means of laser Doppler vibrometry technique. The measurements acquired far from the ablation point demonstrate oscillations of high amplitude and low decay. For all the studied samples, realized in polystyrene and polymethylmethacrylate of two different molecular weights, ablation generates mechanical excitation of the structure, which propagates all over the bulk as vibrational modes and stress waves

Regulation of the orphan nuclear receptor Nr2f2 by the DFNA15 deafness gene Pou4f3.

Hair cells are the mechanotransducing cells of the inner ear that are essential for hearing and balance. POU4F3--a POU-domain transcription factor selectively expressed by these cells--has been shown to be essential for hair cell differentiation and survival in mice and its mutation in humans underlies late-onset progressive hearing loss (DFNA15). The downstream targets of POU4F3 are required for hair cell differentiation and survival. We aimed to identify such targets in order to elucidate the molecular pathways involved in hair cell production and maintenance. The orphan thyroid nuclear receptor Nr2f2 was identified as a POU4F3 target using a subtractive hybridization strategy and EMSA analysis showed that POU4F3 binds to two sites in the Nr2f2 5' flanking region. These sites were shown to be required for POU4F3 activation as their mutation leads to a reduction in the response of an Nr2f2 5' flanking region reporter construct to POU4F3. Immunocytochemistry was carried out in the developing and adult inner ear in order to investigate the relevance of this interaction in hearing. NR2F2 expression in the postnatal mouse organ of Corti was shown to be detectable in all sensory epithelia examined and characterised. These data demonstrate that Nr2f2 is a direct target of POU4F3 in vitro and that this regulatory relationship may be relevant to hair cell development and survival

Treatment of metastatic uveal melanoma with intravenous fotemustine

The purpose of the present study was to retrospectively evaluate the safety and activity of intravenous fotemustine in patients with metastatic uveal melanoma. We report on a series of 25 consecutive patients diagnosed with metastatic uveal melanoma. Fotemustine was administered intravenously as a first-line treatment to all patients. Thrombocytopenia and leukopenia (any grade) were observed in 60 and 52% of patients, respectively. Only two patients discontinued treatment because of toxicity (G3 thrombocytopenia), whereas all other patients were discontinued for progressive disease. Two partial responses were observed. Nine patients had stable disease (disease control rate = 44%). The median survival duration was 13.9 months, and the 1-year survival rate was 60%. Intravenous fotemustine is well tolerated and could improve the outcome of metastatic uveal melanoma patients with or without liver involvement, although a randomized prospective trial is required to confirm these results. Melanoma Res 23:196-198 (c) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

Hypofractionated irradiation of infra-supraclavicular lymph nodes after axillary dissection in patients with breast cancer post-conservative surgery: Impact on late toxicity

Background: The aim of the present work was to analyse the impact of mild hypofractionated radiotherapy (RT) of infra-supraclavicular lymph nodes after axillary dissection on late toxicity. Methods: From 2007 to 2012, 100 females affected by breast cancer (pT1- T4, pN1-3, pMx) were treated with conservative surgery, Axillary Node Dissection (AND) and loco-regional radiotherapy (whole breast plus infra-supraclavicular fossa). Axillary lymph nodes metastases were confirmed in all women. The median age at diagnosis was 60 years (range 34-83). Tumors were classified according to molecular characteristics: luminal-A 59 pts (59 %), luminal-B 24 pts (24 %), basal-like 10 pts (10 %), Her-2 like 7 pts (7 %). 82 pts (82 %) received hormonal therapy, 9 pts (9 %) neo-adjuvant chemotherapy, 81pts (81 %) adjuvant chemotherapy. All patients received a mild hypofractionated RT: 46 Gy in 20 fractions 4 times a week to whole breast and infra-supraclavicular fossa plus an additional weekly dose of 1,2 Gy to the lumpectomy area. The disease control and treatment related toxicity were analysed in follow-up visits. The extent of lymphedema was analysed by experts in Oncological Rehabilitation. Results: Within a median follow-up of 50 months (range 19-82), 6 (6 %) pts died, 1 pt (1 %) had local progression disease, 2 pts (2 %) developed distant metastasis and 1 subject (1 %) presented both. In all patients the acute toxicity was mainly represented by erythema and patchy moist desquamation. At the end of radiotherapy 27 pts (27 %) presented lymphedema, but only 10 cases (10 %) seemed to be correlated to radiotherapy. None of the patients showed a severe damage to the brachial plexus, and the described cases of paresthesias could not definitely be attributed to RT. We did not observe symptomatic pneumonitis. Conclusions: Irradiation of infra-supraclavicular nodes with a mild hypofractionated schedule can be a safe and effective treatment without evidence of a significant increase of lymphedema appearance radiotherapy related

Role of dynamic holography with photorefractive crystals in a multi-functional sensor for the detection of signature features in movable cultural heritage

This paper is one of a series submitted by the Multi-Encode Project consortium and covers the development of holographic interferometry with dynamic photorefractive crystals. The aim of the first phase of the project is to assess the existing techniques for detection of signatures in various types of artworks. The trademark of our technique is a very high resolution in the fringe pattern. We will show the potentiality of our technique for the present application.MULTIENCOD

Defect growth in model panel paintings by full field interferometry

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