Consolidative thoracic radiation therapy for extensive-stage small cell lung cancer in the era of first-line chemoimmunotherapy: preclinical data and a retrospective study in Southern Italy

Background: Consolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes the real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune responses induced by RT are also presented. Methods: A total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy. Results: Preclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and mitochondrial antiviral-signaling protein (MAVS) related to DNA and RNA release. Clinical data showed that TRT was associated with a good safety profile. Of the 59 patients treated with TRT, only 10% experienced radiation toxicity, while no ≥ G3 radiation-induced adverse events occurred. The median time for TRT onset after cycles of chemoimmunotherapy was 62 days. Total radiation dose and fraction dose of TRT include from 30 Gy in 10 fractions, up to definitive dose in selected patients. Consolidative TRT was associated with a significantly longer PFS than systemic therapy alone (one-year PFS of 61% vs. 31%, p<0.001), with a trend toward improved OS (one-year OS of 80% vs. 61%, p=0.027). Conclusion: Multi-center data from establishments in the South of Italy provide a general confidence in using TRT as a consolidative strategy after chemoimmunotherapy. Considering the limits of a restrospective analysis, these preliminary results support the feasibility of the approach and encourage a prospective evaluation

Weekly docetaxel and epirubicin in treatment of advanced hormone-refractory prostate cancer.

OBJECTIVES: To evaluate the efficacy and safety of a new regimen that combines weekly docetaxel and weekly epirubicin for the treatment of advanced hormone-refractory prostate cancer. METHODS: Docetaxel 30 mg/m2 and epirubicin 30 mg/m2 were intravenously administered on a weekly basis, for a maximum of 24 cycles. The therapy was discontinued after the first 12 cycles in the patients who responded or had stable disease and was resumed as soon as any signs of progression were noted. RESULTS: Of the 38 evaluable patients, 26 achieved a confirmed greater than 50% decrease in prostate-specific antigen level (68.4%, 95% confidence interval [CI] 51.2% to 82.0%). The median response duration was 8.8 months (95% CI 6.2 to 11.8), and the median time to progression was 7.4 months (95% CI 5.6 to 9.6). Pain was rapidly reduced in 24 (72.7%, 95% CI 54.2 to 86.7) of the 33 patients who were symptomatic at baseline. Of the 38 patients, 21 resumed therapy after the planned interruption; of these, 3 had a prostate-specific antigen response (14.2%) and 12 had stable disease (57.1%). The regimen was well tolerated. Grade 3 neutropenia occurred in 15.7% of the patients, grade 3 anemia in 13.1%, and grade 3 thrombocytopenia in 7.8%. CONCLUSIONS: The results of this study have suggested the feasibility and tolerability of the combination of weekly docetaxel and weekly epirubicin, which led to a rapid and long-lasting decrease in prostate-specific antigen levels and a palliative response in patients with advanced hormone-refractory prostate cancer

Pneumotorace spontaneo da metastasi polmonare di sarcoma della coscia

Relapsing spontaneous pneumothorax can be the first manifestation of pulmonary metastases of soft tissues sarcomas. Standard imaging tecniques and computed tomography may not be able to detect small malignant cystic lesion or to distinguish between them and benign bollous lesions. We report the case of a 33 year-old male who, in the past, underwent surgical treatment for a synovial sarcoma of the inferior limb. The patient was admitted to our hospital because of right spontaneous pneumothorax; both chest x-ray and CT scan didn't detect any metastatic pulmonary lesion. A few days after the discharge the patient was readmitted because of relapsed pneumothorax; high-definition CT of the chest revealed a pulmonary cystic lesion that was resected thoracoscopically. Histological examination revealed a pulmonary metastases of synovial sarcoma

Effect of neoadjuvant epirubicin and total androgen blockade on complete pathological response in patients with clinical stage T3/T4 prostate cancer.

AIMS: Most patients with stage T3-T4 prostate cancer experience disease relapse despite radiation and/or hormonal therapy, and their management remains controversial. We investigated the feasibility of, and the pathological response induced by neoadjuvant chemo-hormonal treatment in men with clinical stage T3/T4. METHODS: Fifteen patients underwent neoadjuvant therapy consisting of weekly intravenous infusions of epirubicin 30mg/m(2) and total androgen blockade (TAB) for three months before undergoing radical prostatectomy, after which all received locoregional conformal radiotherapy (66Gy) and then continued with TAB and three additional months of epirubicin. RESULTS: After neoadjuvant therapy, PSA levels decreased in all 15 patients and became undetectable in two. None of the patients achieved a complete pathological response, but a 35-75% reduction in tumour size was observed in all cases, and all the patients were able to undergo successful prostatectomy. Pathological assessments of the surgical specimens revealed negative margins in 13 patients. After a median follow-up of 34 months (range 11-62), 14 patients (93%) are still clinically and biochemically disease free. No grade 3 or 4 complications occurred. CONCLUSION: This study suggests that neoadjuvant treatment with epirubicin and TAB is feasible and well tolerated in patients with clinical stage T3-T4 prostate cancer

Biological characterization of fusapyrone and deoxyfusapyrone, two bioactive secondary metabolites of Fusarium semitectum

Fusapyrone (1) and deoxyfusapyrone (2), two alpha-pyrones originally isolated from rice cultures of Fusarium semitectum, were tested in several biological assays. Compounds 1 and 2 showed considerable antifungal activity against several plant pathogenic and/or mycotoxigenic filamentous fungi, although they were inactive toward yeasts isolated from plants and the Gram-positive bacterium Bacillus megaterium in disk diffusion assays. Compound 1 was consistently more active than 2. Among the tested fungi, Fusarium species were the least sensitive to the two pyrones, while Alternaria alternata, Ascochyta rabiei, Aspergillus flavus, Botrytis cinerea, Cladosporium cucumerinum, Phoma tracheiphila, and Penicillium verrucosum were the most sensitive. Compounds 1 and 2 also showed good inhibitory activity toward agents of human mycoses. Aspergilli were the most sensitive, while some species-specific variability was found among the Candida spp. In an Artemia salina larvae bioassay, 1 was not toxic at the highest concentration tested (500 mu M), whereas the LC50 of 2 was 37.1 mu M (21.8 mu g/mL). Neither 1 nor 2 was phytotoxic in a panel of assays that monitored plant-cell toxicity, as well as wilt-, chlorosis-, and necrosis-inducing activity. Moreover, 2 stimulated the root elongation of tomato seedlings at doses of 10 and 100 mu M. In consideration of the biological activities evidenced in this study, 1 and 2 appear to be potential candidates for biotechnological applications, as well as good models for studies on mechanism(s) of action and structure-activity relationships

VAT photopolymerization 3D printing optimization of high aspect ratio structures for additive manufacturing of chips towards biomedical applications

Organ-on-chip and Lab-on-chip are microfluidic devices widely applied in the biomedical field. They are traditionally produced by soft lithography: starting from a mold fabricated by optical photolithography, a Pol-ydimethylsiloxane (PDMS) device is obtained by casting and baking. While this technique offers the possibility to produce features with high resolution, it is not flexible enough to respond to the necessity of customization and prototyping. In this study, we propose as alternative the production of devices by digital light processing (DLP), a vat photopolymerization technology, in combination with a commercially available, biocompatible resin. Studying the process factors by a statistical methodology called Design of Experiment (DoE), we were able to achieve small features with high aspect ratio (60). DoE method allowed us to have a deep understanding of the process without the need of any physical inspection of the involved phenomena, and to generate empirical models, correlating the process factors to the dimensions of the final printed object. We proved that this opti-mization was beneficial also in terms of transparency (evaluated by UV-Vis spectrophotometry), and mechanical strength (evaluated by a compression test) of the printed resin. Finally, a proof-of-concept microfluidic device was fabricated, sealed to a PDMS membrane through an oxygen plasma treatment, and tested against leakage on a microfluidic circuit for one week. As result, we proved that DLP printing is not only a suitable method to develop microfluidic devices, but if correctly optimized it can also reproduce small features in the order of tens of micrometers rapidly

Reticulocytes can represent an early indicator of erythropoietic response to Darbepoetin alfa in the anemia by chemotherapy

Background: Darbepoetin is a new drug active in anemia from chemotherapy and 2-to 3- times longer serum half life then recombinant-human Epo (rHuEPO). Reticulocytes can constitute an useful parameter to check the medullar reserve and give an indication of the erythropoietic answer. Methods: 42 patients in chemotherapy were randomised in 3 groups: the first two reported severe asthenia and have been deal respective with (I) darbepoetin 2.25μg/kg once weekly or (II) rHuEPO 150 U/Kg three times weekly; the third group (III), used like control, did not report relevant asthenic symptoms. The study evaluated time zero, after 4 and 8 weeks hemoglobin, reticulocyte count,serum ferritin, transferrin and iron. Results: The group treated with darbepoetin reported an increase of Hb after 4 weeks of approximately 2 g/dl if the starting value were >10 g/dl (8pts), instead patients with values of Hb <10g/dl evidenced a lower improvement of Hb (approximately 1 g/dl after 8 weeks). In the same group 13/15 pts reported an important improvement of reticulocytes. The mean value increased from 12,3 to 30,4μl (range 19–66); five patients exceeded the 14,5 g/dl of Hb. Group treated with rHuEPO showed a lower increase of reticulocytes after 8 weeks, the mean value increase from 17,2 to 22,6μl (range 13 - 34). In the control group reticulocytes moved by 15,0 to 12,0μl (range 2–16) and hemoglobin value decreased during chemotherapy from 10,5 to 9,7 g/dl. Conclusions: We reported a significantly increase of reticulocytes after four and eight weeks in the group treated with darbepoetin, higher than the group with rHuEPO and much more than the control group. Therefore our study show that darbepoetin is the sooner effective drug in the improvement of anemia. We besides suggest that reticulocyte count is a very important parameter in the prediction of response to the erythropoietic agents