Rates of Adverse Events in Patients With Ulcerative Colitis Undergoing Colectomy During Treatment With Tofacitinib vs Biologics: A Multicenter Observational Study.

INTRODUCTION: Patients with ulcerative colitis (UC) receiving immunosuppressive drugs are at substantial risk of colectomy. We aimed to assess the risk of postoperative complications of tofacitinib exposure before colectomy in comparison with biologics. METHODS: A multicenter, retrospective, observational study was conducted in patients with UC who underwent total colectomy for medically refractory disease, exposed to tofacitinib or a biologic before surgery. Primary outcome was the occurrence of any complication within 30 (early) and 90 (late) days after surgery. Secondary outcomes were the occurrence of infections, sepsis, surgical site complications, venous thromboembolic events (VTE), hospital readmissions, and redo surgery within the same timepoints. RESULTS: Three hundred one patients (64 tofacitinib, 162 anti-tumor necrosis factor-α agents, 54 vedolizumab, and 21 ustekinumab) were included. No significant differences were reported in any outcome, except for a higher rate of early VTE with anti-tumor necrosis factor-α agents ( P = 0.047) and of late VTE with vedolizumab ( P = 0.03). In the multivariate analysis, drug class was not associated with a higher risk of any early and late complications. Urgent colectomy increased the risk of any early (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.06-3.48) complications, early hospital readmission (OR 4.79, 95% CI 1.12-20.58), and early redo surgery (OR 7.49, 95% CI 1.17-47.85). A high steroid dose increased the risk of any early complications (OR 1.96, 95% CI 1.08-3.57), early surgical site complications (OR 2.03, 95% CI 1.01-4.09), and early redo surgery (OR 7.52, 95% CI 1.42-39.82). Laparoscopic surgery decreased the risk of any early complications (OR 0.54, 95% CI 0.29-1.00), early infections (OR 0.39, 95% CI 0.18-0.85), and late hospital readmissions (OR 0.34, 95% CI 0.12-1.00). DISCUSSION: Preoperative tofacitinib treatment demonstrated a postoperative safety profile comparable with biologics in patients with UC undergoing colectomy.

Ustekinumab is a promising option for the treatment of postoperative recurrence of Crohn's disease.

BACKGROUND AND AIM: Postoperative recurrence (POR) following ileocolonic resection is a major concern in patients with Crohn's disease (CD). The role of ustekinumab (UST) in this setting is poorly known. METHODS: All consecutive CD patients with a baseline colonoscopy at 6-12 months from ileocolonic resection showing POR (Rutgeerts score ≥ i2) who were treated with UST after the baseline colonoscopy and with an available post-treatment endoscopy, were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical success, assessed at the end of follow-up. Reasons for clinical failure included mild clinical relapse (Harvey-Bradshaw index 5-7), clinically relevant relapse (Harvey-Bradshaw index > 7), and need for new resection. RESULTS: Forty-four patients were included (mean follow-up: 17.8 ± 8.4 months). The baseline postoperative colonoscopy showed severe POR (Rutgeerts score i3 or i4) in 75.0% of patients. The post-treatment colonoscopy was performed after a mean of 14.5 ± 5.5 months following initiation of UST. Endoscopic success was reported in 22 out of 44 (50.0%) patients, of whom 12 (27.3%) achieved a Rutgeerts score i0 or i1. Clinical success at the end of follow-up was reported in 32 out of 44 patients (72.7%); none of the 12 patients with clinical failure had achieved endoscopic success at post-treatment colonoscopy. CONCLUSIONS: Ustekinumab could be a promising option for the treatment of POR of CD.

Management of radiation-induced oral mucositis in head and neck cancer patients: a real-life survey among 25 Italian radiation oncology centers.

AIM: Radiation-induced oral mucositis (RIOM) is the most frequent side effect in head and neck cancer (HNC) patients treated with curative radiotherapy (RT). A standardized strategy for preventing and treating RIOM has not been defined. Aim of this study was to perform a real-life survey on RIOM management among Italian RT centers. METHODS: A 40-question survey was administered to 25 radiation oncologists working in 25 different RT centers across Italy. RESULTS: A total of 1554 HNC patients have been treated in the participating centers in 2021, the majority (median across the centers 91%) with curative intent. Median treatment time was 41 days, with a mean percentage of interruption due to toxicity of 14.5%. Eighty percent of responders provide written oral cavity hygiene recommendations. Regarding RIOM prevention, sodium bicarbonate mouthwashes, oral mucosa barrier agents, and hyaluronic acid-based mouthwashes were the most frequent topic agents used. Regarding RIOM treatment, 14 (56%) centers relied on literature evidence, while internal guidelines were available in 13 centers (44%). Grade (G)1 mucositis is mostly treated with sodium bicarbonate mouthwashes, oral mucosa barrier agents, and steroids, while hyaluronic acid-based agents, local anesthetics, and benzydamine were the most used in mucositis G2/G3. Steroids, painkillers, and anti-inflammatory drugs were the most frequent systemic agents used independently from the RIOM severity. CONCLUSION: Great variety of strategies exist among Italian centers in RIOM management for HNC patients. Whether different strategies could impact patients' compliance and overall treatment time of the radiation course is still unclear and needs further investigation.

DWI ratios: New indexes for Crohn's disease activity at magnetic resonance enterography?

BACKGROUND: The aim of the study was to provide radiologists and clinicians a rapid tool for assessment of intestinal inflammation in Crohn's disease (CD) patients through quantification of diffusion-weighted imaging (DWI) signal intensity while performing magnetic resonance enterography (MRE). MATERIALS AND METHODS: A monocentric retrospective study was conducted between September 2018 and July 2021 on CD patients who underwent MRE. Two radiologists measured signal intensity on DWI scans at the highest b-value (800 s/mm2) within pathologic intestinal walls, lymph nodes, spleen and psoas muscle and calculated the relative ratios. Spearman, Mann-Whitney and Jonckheere-Terpstra tests were applied for estimating correlation among ratios, significant differences between the two patient groups and determining the trend in relation to endoscopic classes. Wilcoxon's and Cronbach's alpha tests were employed for comparison of DWI measurements and ratios between the two observers. RESULTS: Fifty-nine patients were enrolled in the study. In the non-surgical group, correlation has been found among Simple Endoscopic Score for Crohn's Disease (SES-CD) classes and the different ratios: bowel/spleen (p = 0.034), bowel/psoas (p = 0.008) and bowel/lymph node (p = 0.010). Within the surgical group, positive correlation was found only between bowel/lymph node ratio and bowel/psoas ratio (p = 0.014). The J-T test demonstrated an increasing monotonic trend for bowel/psoas ratio and bowel/lymph node ratio and SES-CD classes. Inter-reader evaluation demonstrated no statistical differences for DWI measurements and high degree of concordance for the final ratios. CONCLUSION: DWI ratios correlate with endoscopic classes in non-surgical patients and have inter-observer reproducibility.

Palliative Care and End-of-Life Issues in Patients with Brain Cancer Admitted to ICU.

Background and Objectives: Palliative care is an interdisciplinary medical specialty focused on improving the quality of life of critically ill patients, including those with frailty, during their illness. Materials and Methods: We conducted an extensive literature review on Pubmed focusing on palliative care in neuro-oncology patients admitted to intensive care units (ICUs). Results: We identified 967 articles and, after excluding 952 articles in accordance with the PRISMA flow chart, we included a total of 15 articles in the final selection. The potential role of palliative care in neuro-oncology appears necessary to ensure comprehensive end-of-life patient care. However, this seems underestimated and poorly applied, especially in the context of intensive care units. Medical personnel also face ethical dilemmas, considering not only the pathology but also the socio-spiritual context of the patient. In addition, caregivers' understanding of prognosis and realistic goals is critical for optimal end-of-life management. Conclusions: The provision of palliative care to neuro-oncological patients admitted to ICU is a complex challenge supported by fragmented evidence. Additional research on palliative care and communication about end-of-life care in the neuro-oncology and neuro-ICU setting is needed.

Ultrasonography Tight Control and Monitoring in Crohn's Disease During Different Biological Therapies: A Multicenter Study.

BACKGROUND & AIMS: Bowel ultrasonography (BUS) is a noninvasive tool for evaluating bowel activity in Crohn's disease (CD) patients. Aim of our multicenter study was to assess whether BUS helps to monitor intestinal activity improvement/resolution following different biological therapies. METHODS: Adult CD patients were prospectively enrolled at 16 sites in Italy. Changes in BUS parameters [i.e. bowel wall thickening (BWT), lesion length, echo pattern, blood flow changes and transmural healing (TH: normalization of all BUS parameters)] were analyzed at baseline and after 3, 6 and 12 months of different biological therapies. RESULTS: One hundred eighty-eight out of 201 CD patients were enrolled and analyzed (116 males [62%]; median age 36 years). Fifty-five percent of patients were treated with adalimumab, 16% with infliximab, 13% with vedolizumab and 16% with ustekinumab. TH rates at 12 months were 27.5% with an NNT of 3.6. TH at 12 months after adalimumab was 26.8%, 37% after infliximab, 27.2% after vedolizumab and 20% after ustekinumab. Mean BWT improvement from baseline was statistically significant at 3 and 12 months (P < .0001). Median Harvey-Bradshaw index, C-reactive protein and fecal calprotectin decreased after 12 months from baseline (P < .0001). Logistic regression analysis showed colonic lesion was associated with a higher risk of TH at 3 months and a greater BWT at baseline was associated with a lower risk of TH at 3 months [P = .03 (OR 0.70, 95% CI 0.50-0.97)] and 12 months [P = .01 (OR 0.58, 95% CI 0.38-0.89)]. At 3 months therapy optimization during the study was the only independent factor associated with a higher risk of no ultrasonographic response [P = .02 (OR 3.34, 95% CI 1.18-9.47)] and at 12 months disease duration [P = .02 (OR 3.03, 95% CI 1.15-7.94)]. CONCLUSIONS: Data indicate that BUS is useful to monitor biologics-induced bowel activity improvement/resolution in CD.

An Objective Comparison of Vedolizumab and Ustekinumab Effectiveness in Crohn's Disease Patients' Failure to TNF-Alpha Inhibitors.

INTRODUCTION: The use of ustekinumab and vedolizumab as second-line therapies in patients with Crohn's disease (CD) in which tumour necrosis factor alpha inhibitors (TNFi) failed is still debated. The aim of this study was to compare, in a large multicenter observational retrospective cohort, the effectiveness of ustekinumab and vedolizumab as second-line therapies, as assessed by clinical and objective outcomes including endoscopy and gastrointestinal imaging. METHODS: Clinical response, remission, and steroid-free remission at weeks 26 and 52 were evaluated in a retrospective propensity score-weighted and propensity score-matched cohort of patients in which TNFi failed. Objective response and remission were evaluated by 1 or more techniques among endoscopy, magnetic resonance/computed tomography enteroclysis, and small bowel ultrasound. RESULTS: A total of 470 patients with CD (239 treated with ustekinumab and 231 treated with vedolizumab) were included in the study. At week 26, clinical outcomes were similar between the 2 groups. At week 52, clinical remission (ustekinumab 42.5% vs vedolizumab 55.5%, P = 0.01) and steroid-free remission (ustekinumab 40.6% vs vedolizumab 51.1%, P = 0.038) rates were significantly higher in vedolizumab-treated patients. Three hundred two patients (hundred thirty-five treated with ustekinumab and hundred sixty-seven treated with vedolizumab) had an objective evaluation of disease activity at baseline and week 52. At week 52, objective response and remission rates were similar between the 2 groups. Clinical response at week 26 predicted steroid-free remission at week 52 in both ustekinumab-treated and vedolizumab-treated patients. Safety profiles were similar between the 2 groups. DISCUSSION: In patients with CD in which TNFi failed, both ustekinumab and vedolizumab showed similar clinical effectiveness after 26 weeks of treatment. At 1 year, vedolizumab was associated with a higher rate of clinical remission when compared with ustekinumab. However, no difference was observed between the 2 groups when objective outcomes were investigated at this time point.

A propensity score weighted comparison of vedolizumab and adalimumab in Crohn's disease.

BACKGROUND AND AIM: There are no head-to-head randomized controlled trials between biologics in Crohn's disease (CD). We aimed to perform a multicenter, real-life comparison of the effectiveness of vedolizumab (VDZ) and adalimumab (ADA) in CD. METHODS: Data of consecutive patients with CD treated with VDZ and ADA from January 2016 to April 2019 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease. The effectiveness was evaluated at 12, 52 weeks, and as failure-free survival at the end of follow up. Propensity score analysis was performed using the inverse probability of treatment weighting method. RESULTS: Five hundred eighty-five treatments (VDZ: n = 277; ADA: n = 308) were included (median follow-up: 56.0 weeks). After 12 weeks, a clinical response was achieved in 64.3% patients treated with VDZ and in 83.1% patients treated with ADA (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.38-1.10, P = 0.107), while at 52 weeks, a clinical response was observed in 54.0% patients treated with VDZ and in 69.1% patients treated with ADA (OR 0.77, 95% CI 0.45-1.31, P = 0.336). Cox survival analysis weighted for propensity score showed no significant difference in the probability of failure-free survival between the two drugs (hazard ratio = 1.20, 95% CI 0.83-1.74, P = 0.340). Post-treatment endoscopic response and mucosal healing rates were similar between the two groups (endoscopic response: 35.3% for VDZ and 25.5% for ADA, P = 0.15; mucosal healing: 31.8% for VDZ and 33.8% for ADA, P = 0.85). CONCLUSIONS: In the first study comparing VDZ and ADA in CD via propensity score analysis, the drugs showed comparable effectiveness and a similar safety profile.

SPOSAB ABP 501: A Sicilian Prospective Observational Study of Patients with Inflammatory Bowel Disease Treated with Adalimumab Biosimilar ABP 501.

BACKGROUND AND AIM: There are few clinical data on Adalimumab (ADA) biosimilars in inflammatory bowel disease. We aimed to perform a multicenter, observational, prospective study on safety and effectiveness of ADA biosimilar ABP 501 in patients with inflammatory bowel disease. METHODS: All consecutive patients from the cohort of the Sicilian Network for Inflammatory Bowel Disease treated with ADA biosimilar ABP 501 from February 2019 to February 2020 were enrolled. Patients were divided into three groups: group A, naïve to ADA and naïve to anti-tumor necrosis factors; group B, naïve to ADA and previously exposed to anti-tumor necrosis factors; and group C: switched from ADA originator to ABP 501. RESULTS: A total of 559 patients (median age 39 years; Crohn's disease 88.0%, ulcerative colitis 12.0%) were included, with a follow-up time of 403.4 patient-years. Thirty-six serious adverse events occurred in 36 patients (6.4%; incidence rate [IR]: 8.9 per 100 person-years [PY]). The IR of serious adverse events was higher among patients in group A compared with group C (17.4 vs 4.8 per 100 PY; IR ratio = 3.61; P < 0.001) and among patients in group B compared with group C (16.4 vs 4.8 per 100 PY; IR ratio = 3.42; P = 0.041). Among ADA-naïve patients (group A + B), 188 (85.8%) had a clinical response after 12 weeks, including 165 (75.3%) who achieved steroid-free remission. Higher treatment persistence estimates were reported for patients in group C compared with groups A and B (log-rank P < 0.001). CONCLUSIONS: Safety and effectiveness of ABP 501 seem to be overall similar to those reported for ADA originator. Switching from originator to ABP 501 was safe and effective.

Diagnostic accuracy of faecal calprotectin in a symptom-based algorithm for early diagnosis of inflammatory bowel disease adjusting for differential verification bias using a Bayesian approach.

BACKGROUND: Diagnostic delay in IBD is a major problem and diagnosis is frequently arrived when irreversible damage has already occurred. This study evaluated accuracy of faecal calprotectin (fCAL) integrated with diagnostic criteria for early diagnosis of IBD in a primary care setting. METHODS: General practitioners (GPs) were trained to recognize alarm symptoms for IBD classified as major and minor criteria. Fulfilment of one major or at least two minor criteria was followed by free fCAL testing and a visit by an IBD specialist and follow-up over 12 months. All patients with positive fCAL testing, i.e., ≥70 µg/g underwent colonoscopy. The diagnostic accuracy of fCAL was estimated after adjusting for differential-verification bias following a Bayesian approach. RESULTS: Thirty-four GPs participated in the study and 133 patients were tested for fCAL between July 2016 and August 2017. Positivity of fCAL was seen in 45/133 patients (34%) and a final IBD diagnosis was made in 10/45 (22%). According to the threshold of 70 µg/g, fCAL achieved a sensitivity of 74.8% (95%CI: 39.10-96.01%), a specificity of 70.4% (95%CI: 61.76-78.16%) and an overall diagnostic accuracy of 70.6% (95%CI: 61.04-78.37%). As for prognostic accuracy, despite positive predictive value being low, 21.9% (95%CI: 11.74-35.18%), the negative predictive value was definitely higher: 96.2% (95%CI: 84.96-99.51%). CONCLUSIONS: fCAL with a threshold set at 70 µg/g seems to represent a potentially reliable negative test to be used in primary care settings for patients with symptoms suggestive of IBD.

Mitigating the Risk of Tofacitinib-induced Adverse Events in the Elderly Population with Ulcerative Colitis.

BACKGROUND AND AIMS: Older patients with ulcerative colitis treated with tofacitinib are at risk for major cardiovascular events, thromboembolism, herpes zoster, and malignancies and, accordingly, its use is limited by the regulatory authorities. The aim of the present study was to evaluate the occurrence of adverse events and potential preventive measures. METHODS: We retrospectively evaluated patients treated with tofacitinib, divided into two groups according to comorbidities and age. Patient- and disease-related variables were recorded [primary non-response, loss of response, and persistence], together with deviations from the recommended induction regimen, ie, dose reduction, and concomitant treatments with anti-thrombotic therapy. RESULTS: The age-adjusted Charlson comorbidity index of Group 1 [n = 30] was ≥2 and that of Group 2 [n = 37] was ≤ 1. No differences were observed for primary or secondary treatment failures. Both groups achieved comparable steroid-free remission rates at 12 months [53% and 46%, respectively]. Herpes zoster occurred in two patients per group, and no more cases occurred after strict recombinant zoster vaccination. No major cardiovascular event or thromboembolism was registered. Half of patients in Group 1 were treated with a reduced induction dose of 5 mg twice daily and 47% were on concomitant anti-thrombotic therapy. Malignancies were registered in two patients from Group 1 and one patient from Group 2. CONCLUSIONS: Modulation of induction dose and anti-thrombotic therapy may have contributed to prevent cardiological events and thromboembolism. The introduction of zoster vaccine virtually eliminated zoster risk after the first cases. Potential malignancies deserve a careful work-up of older patients before treatment start.

Safety and effectiveness of tofacitinib in ulcerative colitis: Data from TOFA-UC, a SN-IBD study.

BACKGROUND: Real-world evidence is needed to determine the value of tofacitinib (TOFA) for the treatment of ulcerative colitis (UC). AIM: To assess the safety and effectiveness of TOFA in clinical practice. METHODS: TOFA-UC is a multicenter, observational study performed among the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). All consecutive patients with UC starting TOFA from its introduction in Sicily (July 2021) to July 2022 were included. RESULTS: 111 patients were included (mean follow-up: 31.7 ± 14.9 weeks; biologic-experienced: 92.8%). Nineteen adverse events were reported (17.1%; incidence rate: 28.2 per 100 patient years), including 11 cases of hypercholesterolemia and 3 infections (no cases of herpes zoster reactivation. At week 8, the rates of clinical response, steroid free clinical remission, and CRP normalization were 74.8%, 45.0%, and 56.9%, respectively, and 68.5%, 51.4%, and 65.2%, respectively, at the end of follow-up. Eighteen patients experienced a loss of response after successful induction (21.7%; incidence rate: 33.2 per 100 patient years). Twenty-six patients (23.4%) discontinued TOFA over time, of whom 3 due to AEs, and 23 to non response or loss of response. CONCLUSIONS: TOFA is safe and effective in patients with UC, including those with history of multiple failures to biological therapies.

Efficacy and Safety of Biological Therapies and JAK Inhibitors in Older Patients with Inflammatory Bowel Disease.

With the introduction of more and more monoclonal antibodies selectively targeting various mediators of the immune system, together with Janus-Kinase (JAK)-inhibitors with variable affinities towards different JAK subtypes, the available therapeutic options for the treatment of inflammatory bowel diseases (IBD) have undergone an acceleration in the last five years. On the other hand, the prevalence of IBD patients over 65-years-old is steadily increasing, and, with this, there is a large population of patients that presents more comorbidities, polypharmacy, and, more frequently, frailty compared to younger patients, exposing them to potentially major risks for adverse events deriving from newer therapies, e.g., infections, cardiovascular risks, and malignancies. Unfortunately, pivotal trials for the commercialization of new therapies rarely include older IBD patients, and those with serious comorbidities are virtually excluded. In the present review, we focus on existing literature from pivotal trials and real-world studies, analyzing data on efficacy/effectiveness and safety of newer therapies in older IBD patients with special emphasis on comorbidities and frailty, two distinct but intercorrelated aspects of the older population since age by itself seems to be of minor importance.

Hypofractionated Radiosurgery for Large or in Critical-Site Intracranial Meningioma: Results of a Phase 2 Prospective Study.

PURPOSE: Radiosurgery is a well-known, safe, and effective technique used in the treatment of intracranial meningiomas. However, single-fraction radiosurgery can lead to high toxicity rates when large-volume or critically located lesions are targeted. Multisession-also called hypofractionated-radiosurgery (hypo-RS) might overcome these limitations. Accordingly, we carried out a prospective phase 2 trial, aiming to establish whether a fractionated RS schedule of 25 Gy in 5 fractions would be safe and effective in treating large (≥ 3 cm) and/or critically located (<3 mm from critical structures) grade 1 intracranial meningiomas. The main aim was to evaluate the safety of hypo-RS in terms of absence of adverse events. The secondary aim was to evaluate tumor response in terms of local control, defined as stability or reduction of lesion volume. METHODS AND MATERIALS: We prospectively enrolled patients with diagnoses of grade 1 meningiomas, large size and/or critically located lesions, either histologically diagnosed or imaging defined. Additional inclusion criteria were signed informed consent, an age of ≥18 years, and Karnofsky Performance Status ≥70. RESULTS: Between 2011 and 2016, 178 patients were consecutively enrolled. The median follow-up was 53 months (range, 4-101 months). Overall, the toxicity rate was 12.7% (21 of 166 patients). At a 5-year minimum follow-up, the patients' toxicity rates were 11.7 % (9 of 77 patients). Symptom evaluation at both 3-year and last follow-up showed an improvement in most of the patients. Five-year local tumor control was 97% (95% confidence interval, 92%-99%). CONCLUSIONS: Hypo-RS schedule of 25 Gy in 5 fractions is a well-tolerated option in the treatment of large-volume and/or critically located benign meningiomas. Early results suggest favorable local control, although longer-term follow-up is needed.

Combining a Customized Immobilization System with an Innovative Use of the ExacTrac System for Precise Volumetric Modulated Arc Therapy of Challenging Forearm Sarcomas.

High-precision image-guided radiation therapy (RT) for tumors abutting the appendicular skeleton may mean technical difficulties and concerns among practitioners. This technical note addresses the specific challenge for normofractionated image-guided RT of a tumor target in a forearm through an unconventional use of a treatment verification system usually devoted to stereotactic RT.

Introducing Radiotherapy in Metastatic Merkel Cell Carcinoma Patients with Limited Progression on Avelumab: An Effective Step against Primary and Secondary Immune Resistance?

PURPOSE: To investigate the ability of radiotherapy (RT) to prolong progression-free survival (PFS) and to report treatment-related toxicities among oligoprogressive metastatic Merkel cell carcinoma (mMCC) patients on avelumab. METHODS: We retrospectively collected clinical data on mMCC patients who underwent radiotherapy for limited progression on avelumab. Patients were categorized as primary or secondary immune refractory depending on the time of onset of resistance to immunotherapy (at the first or subsequent follow-up visits after avelumab initiation). Pre- and post-RT PFS were calculated. Overall survival (OS) from the first progression treated with RT was also reported. Radiological responses and toxicities were evaluated according to the irRECIST criteria and RTOG scoring system, respectively. RESULTS: Eight patients, including five females, with a median age of 75 years, met our inclusion criteria. The median gross tumor and clinical target volumes at first progression on avelumab were 29.85 cc and 236.7 cc, respectively. The treatment sites included lymph node, skin, brain, and spine metastases. Four patients received more than one course of RT. Most patients were treated with palliative radiation doses (mainly 30 Gy in 3 Gy/day fractions). Two patients were treated with stereotactic RT. Five/eight patients were primary immune refractory. The objective response rate at the first post-RT assessment was 75%, whereas no local failure was reported. The median pre-RT PFS was 3 months. The pre-RT PFS was 37.5% at 6 months and 12.5% at 1 year. The median post-RT PFS was not reached. The post-RT PFS was 60% at 6 months and 1 year. The post-RT OS was 85.7% at 1 year and 64.3% at 2 years. No relevant treatment-related toxicity was observed. After a median follow-up of 18.5 months, 6/8 patients are still alive and continuing on avelumab therapy. CONCLUSIONS: Adding radiotherapy to mMCC patients with limited progression on avelumab seems to be safe and effective in prolonging the successful use of immunotherapy, regardless of the type of immune refractoriness.

Low Adherence is Associated with Chronic Active Disease in Ulcerative Colitis: A Retrospective Study from a Single Referral Center.

Purpose: New therapeutic approaches for ulcerative colitis (UC) are now available, but there is still no robust evidence for predictors of poor outcomes. We aimed to evaluate the factors associated with a chronic active UC disease course. Patients and Methods: Data of all UC outpatients followed for at least 3 years after diagnosis between 2005 and 2018 were retrospectively collected. The primary aim was to identify risk factors for chronic active disease 3 years after diagnosis. Moreover, the following variables were investigated: proximal disease extension or disease regression, proctocolectomy, early use of biologics (BIO) or immunomodulators (IMM), hospitalization, colorectal cancer, and adherence. We defined adherence as both, taking the prescribed therapy and constancy in scheduled follow-up visits. Results: A total of 345 UC patients followed for a median period of 82 months were included. Patients with extensive colitis at diagnosis had a higher rate of chronic active disease 3 years after diagnosis (p<0.012) together with a higher rate of surgery (p<0.001) at maximum follow-up. Patients with pancolitis showed significant disease regression over time (51%) without differences in treatment. The only factor associated with chronic active disease was non-adherence (p < 0.03; OR 0.49, 95% CI: 0.26-0.95). Adherent patients developed chronic active disease (p<0.025) less frequently but did receive more frequent IMM (p<0.045) or BIO (p<0.009) therapy. Conclusion: Patients diagnosed with pancolitis were more likely to have chronic active disease and to undergo colectomy. The only predictor for developing chronically active UC regardless of disease extension was the lack of adherence to therapy within the first 3 years after diagnosis, underlining the importance of tight control of UC patients and the need to timely identify potential risk factors for non-adherence.

Considerations on surgery invasiveness and response and toxicity patterns in classic palliative radiotherapy for acrometastases of the hand: a hint for a potential role of stereotactic body radiation therapy? A case report and literature review.

Background: The rarity of hand acrometastases hampers the consensus-building for their optimal management among the involved oncology professionals. In the current literature, demolitive surgery overcomes the use of palliative radiotherapy, which proved to be ineffective in more than 30% of cases treated with classic palliative dose schemes, carrying also a not negligible radiation-related adverse event rate. Against this background, stereotactic body radiation therapy (SBRT) could emerge as a well-balanced therapeutic option. Case summary: Here we describe the methods and outcomes of a SBRT treatment of a painful and function-limiting hand acrometastasis in a patient with a history of stage IIIB lung adenocarcinoma. We delivered a total dose of 30 Gy in five daily fractions to a soft-tissue metastasis abutting the fifth metacarpal bone through the SBRT protocol generally used for intracranial treatments. A few weeks later, the patient reported a clinical complete response with acrometastasis and pain disappearance, function recovery, and no significant toxicity. The acrometastasis was the first sign of an atypical cancer progression. Conclusions: SBRT for hand acrometastases is feasible and might have the best therapeutic profile among the currently available treatment options for this rare clinical scenario. Larger investigations are needed to confirm the present single-case experience.

Psychological impairment in inflammatory bowel diseases: the key role of coping and defense mechanisms.

A comprehensive investigation of psychological features in chronic patients is very important for tailoring effective treatments. In this study we tested anxiety, depression, health related quality of life (HR-QoL), alexithymia, coping styles, and defense mechanisms, in eighty-four patients with Crohn disease (CD) and ulcerative colitis (UC). Participants reported low to moderate HRQoL and anxiety, apart from alexithymia. Women experienced lower QoL and higher levels of anxiety and depressive symptoms. Coping and defense strategies were related to distress symptoms and QoL. Positive attitude and principalization, showed negative associations with depression, anxiety and alexithymia and were also found to be associated with mental health. CD patients used significantly more turning against objects (p=0.02) and projections (p=0.01) and UC patients used more reversal (p=0.04). Elderly women showed higher anxiety symptoms and lower perceived QoL. Multiple regression analysis revealed anxiety and depression were independently associated with QoL. Significant differences emerged in defense styles among CD and UC. CD participants used more maladaptive coping and defense styles which were related to mental distress, depression and anxiety, together with higher level of alexithymia. Findings suggest that psychological aspects play a key role in mental health in patients suffering from inflammatory bowel diseases. A multi-integrated clinical strategy including psychotherapeutic interventions should be considered in treating CD and UC.

Towards Personalization of Planning Target Volume Margins Fitted to the Abdominal Adiposity in Localized Prostate Cancer Patients Receiving Definitive or Adjuvant/Salvage Radiotherapy: Suggestive Data from an ExacTrac vs. CBCT Comparison.

BACKGROUND/AIM: This study aimed to assess whether the patient's abdominal adiposity affects the performance of the Exactrac imaging system compared to the cone beam computed tomography (CBCT)-based setup, which was used as the reference positioning for the image-guided radiotherapy (IGRT) delivery to patients with localized prostate cancer. PATIENTS AND METHODS: The daily positionings of patients with localized prostate cancer undergoing definitive or adjuvant/salvage radiotherapy (RT) were analyzed. The abdominal fat areas and pelvic incidence angle were determined on the CT simulation for each patient. A couple of ExacTrac images and a CBCT were acquired daily to verify the patient setup. We recorded every daily set of the three residual translational errors detected on the CBCT after the ExacTrac-based setup. These sets were clustered within three different thresholds (0.1 mm, 0.2 mm, and 0.3 mm), for each of which the influence of adipose tissues on Exactrac accuracy was assessed as the percentage of sub-threshold displacements as the fat parameters varied. A full bladder and empty rectum preparation protocol was adopted as much as possible. RESULTS: From the assessment of 1,770 daily positionings in 55 patients (38 definitive RT, 17 adjuvant/salvage RT), a good agreement between ExacTrac and CBCT could be inferred, which was quite robust against slight variations in the bladder and rectal filling, and the presence or not of the prostate. The percentages of above-threshold corrections increased with increasing abdominal fat, which therefore seemed to reduce the ExacTrac accuracy. This might be influenced by any intrafraction prostate displacement, likely induced by abdominal respiratory movements, and are more pronounced among overweight men. CONCLUSION: Our results promote the CBCT use over ExacTrac for IGRT of overweight patients with localized prostate cancer, while calling for attention to the probable need for personalization of planning target volume margins depending on the patient's body habitus.