Comparison of local recurrence among early breast cancer patients treated with electron intraoperative radiotherapy vs hypofractionated photon radiotherapy an observational study

Purpose: To evaluate local recurrence (LR) in women with early breast cancer (BC) who underwent intraoperative radiation therapy with electrons particles (IORT-E) or adjuvant hypofractionated external radiotherapy (HYPOFX). Materials and methods: We retrospectively analyzed 470 patients with early BC treated at our center from September 2009 to December 2012. 235 women were treated with breast-conserving surgery and immediate IORT-E (21 Gy/1 fraction) while 235 patients underwent wide excision followed by hypofractionated whole-breast irradiation. Radiotherapy modality was chosen according to an individualized decision based on tumor features, stage, technical feasibility, age, and acceptance to be enrolled in the IORT-E group. Results: After a median follow-up of 6 years, we observed 8 (3.4%) and 1 (0.42%) LR in the IORT-E and in the HYPOFX group (p = 0.02), respectively. The two groups differed in the prevalence of clinical characteristics (p < 0.05): age, tumor size, surgical margins, receptors, ki67, and histology. 4 and 1 woman in the IORT-E and HYPOFX group died of BC, respectively (p = 0.167). OS and DFS hazard ratio [HR] were 2.14 (95% IC, 1.10-4.15) and 2.09 (95% IC, 1.17-3.73), respectively. Conclusion: Our comparison showed that IORT-E and HYPOFX are two effective radiotherapy modalities after conservative surgery in early BC. However, at 6 years a significant higher rate of LR occurred in patients submitted to IORT-E with respect to HYPOFX. This finding may be correlated to some subsets of patients who, depending on the biological characteristics of the BC, may be less suitable to IORT-E

The Susceptibility of Candida albicans to Gamma-Radiations and Ketoco-nazole Depends on Transitional Filamentation

The virulence of C. albicans is associated with the transitional evolution from yeast to filamentous forms. We were interested in the effects amphotericin B (AMB), ketoconazole (KTC) and γ-radiations might have on these broadly defined phenotypes as determined by the CFU procedure. By using collagen gel as the 3-dimensional support of cell culture, diverse experimental conditions were contemplated in order to modulate the differentiation of Candida during sessile and planktonic growth. These conditions included the co-culture with human epithelial and endothelial cells and treatment with farnesol, tyrosol and conditioned medium from P. aeruginosa. The overall results were as follows: 1) The survival of Candida was inhibited by the exposure to γ-radiations, but only after the organism was induced to progress into excess filamentation, while in normal growth conditions it proved to be radioresistant; 2) AMB inhibited the growth of yeast forms, while KTC was specifically toxic to filamentous forms and 3) the combined treatment of filamentous Candida with KTC and γ-radiations resulted in the synergistic inhibition of the organism. These findings indicate that both the radiosensitivity of C. albicans and its response to the synergistic effects of γ-radiations and KTC are filamentation-dependent pharmacological processes

Induction chemotherapy followed by alternating chemo-radiotherapy in stage IV undifferentiated nasopharyngeal carcinoma

In locally advanced undifferentiated nasopharyngeal carcinoma (UNPC), concomitant chemo-radiotherapy is the only strategy that gave better results over radiation alone in a phase III trial. Adding effective chemotherapy to a concomitant chemo-radiotherapy programme may be a way to improve the results further. 30 patients with previously untreated T4 and/or N2–3 undifferentiated nasopharyngeal carcinoma were consecutively enrolled and initially treated with 3 courses of epidoxorubicin, 90 mg/m2, day 1 and cisplatin, 40 mg/m2, days 1 and 2, every 3 weeks. After a radiological and clinical response assessment patients underwent 3 courses of cisplatin, 20 mg/m2/day, days 1–4 and fluorouracil, 200 mg/m2/day, days 1–4, i.v. bolus, (weeks 1, 4, 7) alternated to 3 courses of radiation (week 2–3, 5–6, 8–9–10), with a single daily fractionation, up to 70 Gy. WHO histology was type 2 in 30% and type 3 in 70% of the patients. 57% had T4 and 77% N2–3 disease. All the patients are evaluable for toxicity and response. All but one received 3 courses of induction chemotherapy. Toxicity was mild to moderate in any case. At the end of the induction phase 10% of CRs, 83.3% of PRs and 6.7% of SD were recorded. All the patients but one had the planned number of chemotherapy courses in the alternating phase and all received the planned radiation dose. One patient out of 3 developed grade III–IV mucositis. Haematological toxicity was generally mild to moderate. At the final response evaluation 86.7% of CRs and 13.3% of PRs were observed. At a median follow-up of 31 months, 13.3% of patients had a loco-regional progression and 20% developed distant metastases. The 3-year actuarial progression-free survival and overall survival rates were 64% and 83%. Induction chemotherapy followed by alternating chemo-radiotherapy is feasible and patients' compliance optimal. This approach showed a very promising activity on locally advanced UNPC and merits to be investigated in phase III studies. © 2000 Cancer Research Campaign http://www.bjcancer.co

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

Topical natural-origin polynucleotides in radiation-induced skin and mucosal toxicity

Seventy to 90 percent of patients who have received radiation treatment struggle with radiation skin and mucosal toxicity. The inflicted damage to progenitor cells and local microcirculation makes it more likely that wounds, infections, and fibrosis may occur; lesions of variable severity often co-exist. Acute erythema, hyperpigmentation, and mild desquamation usually wane in weeks and require only minor treatment. Conversely, the management of persistent radiation dermatitis and telangiectasia remains unsatisfactory; chronic lesions may progress to tissue atrophy and disfiguring fibrosis. Protrophic, natural-origin polynucleotides, formulated as Class III medical devices, have long shown to be a reliable topical option to stop the progression of radiation-related lesions. The present review illustrates the rationale of polynucleotides in skin and mucosal radiodermatitis management. It also illustrates the clinical results in a series of exploratory clinical studies carried out with polynucleotide devices over the last decade. The examined studies open the way to the high-level clinical research program, which will develop over the next years

Crystal plasticity and fluid availability govern the ability of titanite to record the age of deformation

Here, we study the relationships of titanite-hosting microdomains, intragrain chemical variations, microstructure and fluids with the aim of deciphering the reliability of titanite U–Pb dating to constrain the age of deformation in mylonitic rocks. We investigate these relationships in a postVariscan amphibolite-facies shear zone developed in the mid-low continental crust (Ivrea-Verbano Zone, Southern Alps, Italy). Quantitative orientation analyses along with textural imaging of titanite are combined with trace-element analyses and U–Pb age dating. Titanite is studied in mm- to cmscale layered rocks showing compositional variation consisting of alternating ‘amphibole-rich’ (i.e., amphibolites) and ‘clinopyroxene/plagioclase-rich’ domains (i.e., calc-silicates). Titanite from amphibolerich domains shows predominance of crystal–plastic deformation features, as abrupt or progressive coreto-rim structures characterized by increasing lattice distortion and local dislocation density, associated with the development of abundant subgrains and rare newly nucleated grains. We suggest that these microstructures form while interacting with small amounts of fluids circulating along the grain boundaries. Consequently, locally the chemistry of titanite is changing. In the clinopyroxene/plagioclaserich domains, titanite is mostly undeformed and rarely shows bending localized in discontinuous narrow rims/tips. In these domains, fluid-mediated replacement reactions are either rare or absent, as also indicated by weak chemical variations across and among grains. These observations suggest different reactivities with respect to the same P-T-fluid conditions of the two compositional domains, which coexist within the same sample at the thin section scale. U–Pb data show correlations with chemical and microstructural domains that differ as function of the composition of the microdomain. This correlation is more apparent within amphibole-rich domains where microstructures characterized by high lattice distortion/dislocations and/or subgrains show significant variations of REE, Zr, Y, Nb, U with respect to the low deformed portion of grains. These titanite domains define an isotopic population providing the youngest (Jurassic) lower intercept age. A less clear correlation between titanite chemistry and microstructures is observed in clinopyroxene/plagioclase-rich domains. Here, the rare titanites showing lattice distortion and minor Sr depletion define a population providing a similar Jurassic lower intercept age. Therefore, our results demonstrate that microstructurally and chemical calibrated U–Pb dating of titanite provides realistic ages of shear zone activity, only in case of predominance of crystal-plastic processes and of local interaction of titanite with small amounts of fluids focused along grain boundaries. Finally, the different footprints recorded by titanite grains strongly depend on the composition of cm- or mm-scale interlayered domains in which titanite occurs