Risankizumab for the treatment of moderate-to-severe psoriasis: A multicenter, retrospective, 1 year real-life study.

Several new biologic agents targeting IL23/Th17 axis, such as risankizumab, have been developed for the treatment of psoriasis. The aim of the present study was to analyze the efficacy and safety of risankizumab in patients with moderate-to-severe psoriasis over a 52-week period. A multicentric retrospective study was conducted in patients who initiated risankizumab between July 2019 and December 2020. Psoriasis Area and Severity Index-PASI was measured at baseline and after 4, 16, 28 and 52 weeks. Clinical responses were evaluated by PASI75, PASI90 and PASI100 at the same timepoints. Potential safety issues and adverse events (AEs) were collected. Univariable and multivariable logistic regressions were performed for variables predicting clinical response. One hundred and twelve patients with psoriasis were included. PASI90 response was achieved by 17.86% of patients at week 4, 72.22% at week 16, 91.0% at week 28 and 95.24% at week 52 (as observed analysis). No associations between the considered variables and the efficacy endpoints were retrieved, influence of variables such as Body Mass Index (BMI), baseline PASI or previous biologics were not shown. No serious safety issues or discontinuations related to adverse events were reported. Risankizumab showed high efficacy and a favorable safety profile, regardless of patient- and disease-related factors.

Predictive factors of lack of response to adalimumab among bio-naive patients suffering from moderate-to severe psoriasis: analysis of a multicenter data collection in Italy.

INTRODUCTION: Efficacy of anti-TNF-a agents seems inferior to IL-17 and IL-23 inhibitors. Nevertheless, after biosimilars approval, anti TNF-a agents are recommended as first-line for psoriatic patients, for economic reasons. METHODS: Predictive factors of response or non-response to adalimumab in bionaive patients who started adalimumab (originator or biosimilar) over 12 years in 9 dermatologic centers in Italy. Effectiveness was assessed with Psoriasis Area and Severity Index (PASI75 and PASI90) at weeks 12, 24 and 48. Multiple logistic regressions were used for variables predicting clinical response; Kaplan-Meier survival curves and Cox regression for drug survival. RESULTS: The drug survival analysis showed reduced hazard ratio of overall discontinuation with male gender and scalp localization. In contrast, baseline PASI and genital psoriasis were significantly associated with increased risk of overall discontinuation. Predictive factors of non-response seemed elevated in patients with baseline PASI, older age groups, previously treated patients with phototherapy, females or patients with palmo-plantar while scalp psoriasis, previous cyclosporine and acitretin appeared as a positive predictive factor. CONCLUSIONS: This real-life analysis might be useful for clinicians in case of bio-naive patients with moderate-to-severe psoriasis and various comorbidities.

Persistence of HPV after radio-chemotherapy in locally advanced cervical cancer.

A causal association of high risk HPV persistent infections with cervical cancer is firmly established by epidemiological and experimental evidence. Since HPV is considered a necessary factor for cervix carcinoma development and disease severity, the HPV DNA persistence may represent an indicator of both therapy effectiveness and risk of recurrence. The presence of HPV in locally advanced cervical carcinoma was analysed at the beginning of therapy, shortly after treatment and during follow-up, in 18 patients with cervix carcinoma treated by radio/chemotherapy. Persistence of HPV DNA sequences was revealed in 62.5% (10/16) of HPV positive patients, in which the HPV type and its physical status were exactly the same as at the onset of therapy, even many years after surgery. Interestingly, in two patients the HPV18 sequence analysis detected the same point mutations in the samples before and after the chemotherapy, and during the follow-up. HPV DNA clearance was associated with a better patient outcome because the majority of the HPV cleared women showed a complete response (6/6), no disease recurrence (4/6), and are still alive. Nevertheless, statistically significant association was seen only with complete responses versus partial or no responses. In conclusion, we demonstrated that HPV DNA positive tumour cells might persist for years in the genital epithelia, even after the surgical removal of the cervix and that HPV DNA detection after therapy is a valid and significant (p=0.03) tool to assess the efficacy of the treatment.

Conservative treatment of reproductive and sexual function in young woman with squamous carcinoma of the vagina.

OBJECTIVE: Primary squamous carcinoma of the vagina in young woman is extremely rare. Conservative management of both sexual and reproductive function poses challenging problems to gynecologic oncologists. METHODS: Between January 2001 and December 2004, four women under 40, nulliparous, with squamous cell carcinoma of the upper third of the vagina, at FIGO Stage I were submitted to conservative surgery of the reproductive/sexual function at our Institution. After written informed consent was obtained, conservative surgical treatment consisting of radical tumorectomy with pelvic lymphadenectomy, in three patients, and partial hemi-vaginectomy plus homolateral paracolpectomy/parametrectomy with pelvic lymphadenectomy, in the forth patient, was carried out. RESULTS: Mean operative time of conservative surgical treatment was 161 min. No intraoperative or postoperative complications were observed. In one patient, definitive pathologic examination revealed microscopic involvement of the paracolpium. Thus, after carrying out laparoscopic ovarian transposition, adjuvant radiotherapy (RT), consisting of pulsed-dose rate brachytherapy and external RT, was delivered in this woman. After a follow-up time of 51, 45, 21 and 9 months, respectively, all patients are regularly menstruating, sexually active and clinically free of disease. CONCLUSION: To our knowledge, this is the first report showing the feasibility and the efficacy of conservative surgery of reproductive and sexual function in young woman with vaginal carcinoma. A larger number of patients and a longer follow-up are needed to validate the safety of this approach.

Postoperative chemoradiotherapy in rectal cancer. Late results of a pilot study.

BACKGROUND/AIMS: It has recently been proven that postoperative radiotherapy combined with fluorouracil showed an increase of survival and local control in patients with rectal cancer. However, hematological and intestinal toxicity also increased. Experimental and clinical studies showed an increased radiation effect with an acceptable toxicity by delivering drug via a continuous intravenous infusion. METHODOLOGY: From 1988 to 1998, 80 patients radically operated on for stages B2-C rectal cancer were irradiated with 3 fractions of 100 cGy per day to a total dose of 5,600 cGy. 34 out of these 80 patients underwent postoperative radiotherapy alone and 46 received radiotherapy combined with concomitant protracted infusion of fluorouracil at doses of 250 mg/m2 per day. RESULTS: After a median follow-up of 54 months, the 5-year overall and disease-free survival were 59% and 54%, respectively, in the combined modality group, as compared to 42% and 34%, respectively, in the radiation alone group. The differences were not significant, but the incidence of local relapse and patients' survival showed a better trend for combined approach. CONCLUSIONS: The data from international literature are in favor of a combined approach, both in preoperative and postoperative treatment of advanced rectal cancer. Adjuvant therapy must be re-evaluated in trials using total mesorectal excision as the standard operative technique.

Postoperative chemoradiotherapy in rectal cancer. Long-term results of a pilot study.

It has recently been proven that postoperative radiotherapy combined with fluorouracil affords an increase in survival and local control in patients with rectal cancer. However, haematological and intestinal toxicity also increase. Experimental and clinical studies have shown an increased effect of radiation with an acceptable toxicity by delivering the drug via continuous intravenous infusion. From 1988 to 1998, 80 patients radically operated on for stage B2-C rectal cancer were irradiated with 3 fractions of 100 cGy per day up to a total dose of 5,600 cGy; 34 of these patients underwent postoperative radiotherapy alone and 46 received radiotherapy combined with concomitant protracted infusion of fluorouracil at doses of 250 mg/m2 per day. After a median follow-up of 60 months, the 5-year overall and disease-free survival rates were 59% and 54%, respectively, in the combined modality group, as compared to 42% and 34%, respectively, in the radiation alone group. The differences were non-significant, but the incidence of local relapse and patient survival showed better trends with the combined approach. The international literature data are in favour of a combined approach in both the preoperative and postoperative treatment of advanced rectal cancer. Adjuvant therapy needs to be re-assessed in trials using total mesorectal excision as the standard operative technique.