Search

Purpose CT findings of hospitalized COVID-19 patients were analyzed during both the first and the second waves of the pandemic, in order to detect any significant differences between the two groups. Methods In this observational, retrospective, monocentric study, all hospitalized patients who underwent CT for suspected COVID-19 pneumonia from February 27 to March 27, 2020 (first wave) and from October 26 to November 24, 2020 (second wave) were enrolled. Epidemiological data, radiological pattern according to the RSNA consensus statement and visual score extension using a semi-quantitative score were compared. Results Two hundred and eleven patients (mean age, 64.52 years ± 15.14, 144 males) were evaluated during the first wave while 455 patients (mean age, 68.26 years ± 16.34, 283 males) were studied during the second wave. The same prevalence of patterns was documented in both the first and the second waves (p = 0.916), with non-typical patterns always more frequently observed in elderly patients, especially the “indeterminate” pattern. Compared to those infected during the first wave, the patients of the second wave were older (64.52 vs.68.26, p = 0.005) and presented a slightly higher mean semi-quantitative score (9.0 ± 2.88 vs. 8.4 ± 3.06, p = 0.042). Age and semi-quantitative score showed a positive correlation (r = 0.15, p = 0.001). Conclusions There was no difference regarding CT pattern prevalence between the first and the second waves, confirming both the validity of the RSNA consensus and the most frequent radiological COVID-19 features. Non-typical COVID-19 features were more frequently observed in older patients, thus should not be underestimated in the elderly population.

Purpose The aim of this retrospective multicentric study was to compare the tumour response rates of Balloon-occluded Transarterial Chemoembolisation (B-TACE) to non-B-TACE using propensity score matching (PSM) in patients with hepatocellular carcinoma and to investigate the clinical benefit, such as lower rates of TACE re-intervention achieved using B-TACE. Material and Methods The B-TACE procedures (n = 96 patients) were compared with a control group of non-B-TACE treatments (n = 434 pts), performed with conventional (cTACE) or drug-eluting microspheres TACE (DEM-TACE). Data were collected from six European centres from 2015 to 2019. Objective responses (OR) and complete response (CR) rates after the first session and the number of TACE re-interventions were evaluated using PSM (91 patients per arm). Results The best target OR after PSM were similar for both B-TACE and non-B-TACE (90.1% and 86.8%, p = 0.644); however, CR at 1–6 months was significantly higher for B-TACE (59.3% vs. 41.8%, p = 0.026). Patients treated with B-TACE had a significantly lower retreatment rate during the first 6 months (9.9%% vs. 22.0%, p = 0.041). Post-embolisation syndrome (PES) rates were 8.8% in non-B-TACE and 41.8% in B-TACE (p Conclusion B-TACE is safe and effective, achieving higher CR rates than non-B-TACE. Patients undergoing B-TACE had a significantly lower retreatment rate within the first 6 months but higher PES rates. Level of Evidence III Level 3, retrospective study.

Treatment response is usually assessed by the response evaluation criteria in solid tumors (RECIST). These criteria may not be adequate to evaluate the response to immunotherapy, considering the peculiar patterns of response reported with this therapy. With the advent of immunotherapy these criteria have been modified to include the evaluation of the peculiar responses seen with this type of therapy (iRECIST criteria), including pseudoprogressions and hyperprogressions. Tumor growth rate (TGR) is a dynamic evaluation that takes into account the kinetics of response to treatment and may help catch the real efficacy of an immunotherapy approach. We performed a retrospective monocentric study to explore the impact of TGR change after nivolumab administration as the second or later line of treatment in patients with metastatic renal cell carcinoma (RCC). We evaluated 27 patients, divided into three categories: Disease control (DC) if there was no PD, lower velocity PD (LvPD) if disease progressed but the TGR at second assessment (TGR2) was lower than the TGR at first assessment (TGR1), higher velocity PD (HvPD) if TGR2 was higher than TGR1. The median OS for the DC group was 11.0 months (95% CI 5.0–17.0) (reference) vs. (not reached) NR (95% CI NR-NR) for LvPD (HR 0.27, 95% CI 0.06–1.30, p 0.102) vs. NR (95% CI NR–NR) for HvPD (HR 0.23, 95% CI 0.06–0.88, p 0.032). There was no difference between LvPD and DC (HR 1.21, 95% CI 0.20–7.28, p 0.838). In patients with metastatic RCC, the second or later line of nivolumab treatment may lead to a deceleration in TGR resulting in an improved survival outcome similar to that observed in patients experiencing tumor regression. In this subgroup, especially in the presence of a clinical benefit, continuing the treatment beyond progression can be recommended.

Purpose Cancer treatments with immune checkpoint inhibitors (ICI) are associated with a unique set of drug toxicities called immune-related adverse events (irAES). The aim of the present study was to describe the radiological manifestation of irAES detectable by CT. Method Retrospective analysis of 284 patients treated with ICI for various types of advanced cancer; of them, 129 patients were selected, all having been treated with single-agent ICI, and all with a baseline CT scan and follow-up scans available at our Institute. CT examinations were reviewed by two radiologists involved in the study with a consensus reading. Imaging findings consistent with irAES were reported and correlated with clinical-laboratory data. Results Immune-related adverse events were found in 25/129 (19.4 %) patients. No statistically significant differences were found in either the prevalence of irAES or in the time of onset of tumour type. Thoracic complications were detected in 14/25 (56.0 %) patients consisting in: 3 radiation recall pneumonia, 3 Transient Asymptomatic Pulmonary Opacities (TAPOs), 3 hypersensitivity pneumonia, 2 diffuse alveolar damage, 2 organizing pneumonia, 1 sarcoid-like reaction. In the remaining 11/25 (44.0 %), there were extra-pulmonary complications: 3 colitis, 4 cholecystitis, 2 pancreatitis and 2 cases of visceral ischemia. Conclusions Radiologists should be aware of the wide spectrum of irAES as they could affect the outcome. Pneumonia is the most frequent irAES; however, the international classification for interstitial lung disease does not seem to be capable of describing all possible drug-related pulmonary toxicities. Additional findings included TAPOs, radiation recall pneumonia and sarcoid-like reaction.

Aim: To evaluate relevance of clinical and molecular factors in adult low-grade gliomas (LGG) and to correlate with survival. Methods: We reviewed records from adult LGG patients from 1991 to 2015 who received surgery and had sufficient tissue to molecular biomarkers characterization. Results: 213 consecutive LGG patients were included: 17.4% were low-risk, according to Radiation Therapy Oncology Group (RTOG) risk assessment. IDH 1/2 mutation, 1p/19q co-deletion, MGMT methylation were found in 93, 50.8 and 65.3% of patients. Median follow-up was 98.3 months. In univariate analysis, overall survival was influenced by extent of resection (p = 0.011), IDH mutation (p

// Alba A. Brandes 1 , Gaetano Finocchiaro 2 , Vittorina Zagonel 3 , Michele Reni 4 , Alessandra Fabi 5 , Claudia Caserta 6 , Alicia Tosoni 1 , Marica Eoli 2 , Giuseppe Lombardi 3 , Matteo Clavarezza 7 , Alexandro Paccapelo 1 , Stefania Bartolini 1 , Luigi Cirillo 8 , Raffaele Agati 8 and Enrico Franceschi 1 1 Department of Medical Oncology, Bellaria-Maggiore Hospitals, Azienda USL, IRCCS Institute of Neurological Sciences, Bologna, Italy 2 Molecular Neuro-Oncology Unit, IRCCS Foundation Carlo Besta, Milan, Italy 3 Department of Clinical and Experimental Oncology, Medical Oncology 1, Veneto Institute of Oncology, IRCCS, Padua, Italy 4 Department of Medical Oncology, IRCCS San Raffaele, Milan, Italy 5 Medical Oncology 1, Regina Elena National Cancer Institute, Rome, Italy 6 Oncology Department, Santa Maria Hospital, Terni, Italy 7 Medical Oncology Unit, Ente Ospedaliero Ospedali Galliera, Genova, Italy 8 Department of Neuroradiology, Bellaria Hospital, IRCCS Institute of Neurological Sciences, Bologna, Italy Correspondence to: Alba A. Brandes, email: // Keywords : glioblastoma, RANO, bevacizumab, fotemustine, ETS Received : January 21, 2017 Accepted : February 08, 2017 Published : February 25, 2017 Abstract BACKGROUND: Disease assessment for recurrent glioblastoma (GBM) represents a challenge, especially with the use of antiangiogenic agents. Moreover, validated neuroradiological predictors of outcome are lacking. Recently, the concept of early tumor shrinkage (ETS) has been developed to better assess the ability of treatments in determining a rapid and remarkable tumor response. The aim of the study was to evaluate the role of ETS in predicting survival of GBM patients treated with BEV METHODS: We examined the radiological data of patients with recurrent GBM treated with bevacizumab (BEV) or fotemustine (FTM) in the randomized phase II AVAREG trial (EudraCT: 2011-001363-46). Radiologic assessments at first disease assessment (day 46) were used to calculate the relative change in the sum of the products of perpendicular diameters of all measurable lesions determined by either T1 contrast and T2/FLAIR. RESULTS: In patients treated with BEV, the best ETS cut-off was reduction of 15% with T1 contrast and of 40% with T2/FLAIR. Adopting this cut-off for T1 contrast radiological changes, ETS was a significant predictor of OS for patients treated with BEV (HR = 0.511, 95%CI:0.269-0.971, p = 0.040). The cut-off obtained for T2/FLAIR was not significantly correlated with OS ( p = 0.102), but we found a trend for correlation with survival when considering the variable as continuous ( p = 0.058). CONCLUSIONS: ETS evaluating T1 contrast reduction is a helpful predictor of survival in patients with recurrent GBM treated with BEV, and if validated in a larger prospective trial could be a helpful surrogate endpoint.

Background: Diffuse grade II and grade III gliomas are actually classified in accordance with the presence of isocitrate dehydrogenase mutation (IDH-mut) and the deletion of both 1p and 19q chromosome arms (1p/19q codel). The role of tumour grading as independent prognostic factor in these group of tumours remains matter of debate. The aim of this study was to determine if grade is an independent prognostic factor and not somehow associated to IDH mutation and 1p/19q status of the tumour. Methods: We analysed 399 consecutive patients with newly diagnosed, histologically proven World Health Organisation (WHO) 2016 grade II or grade III IDH-mut gliomas, assessed by polymerase chain reaction, immunohistochemistry or next-generation sequencing (NGS). Results: The analysis included 399 patients with grade II (n = 250, 62.7%) or grade III (n = 149, 37.3%) diffuse gliomas. Median follow-up time was 105.3 months. Median survival was 148.1 months. In multivariate analysis, grade II (hazard ratio [HR] = 0.342, 95% confidence interval [CI]: 0.221–0.531; P < 0.001) and 1p/19q codeletion (HR = 0.440, 95% CI: 0.290–0.668; P < 0.001) were independently associated with a lower risk for death. The difference in survival remained significant (p = 0.006 in astrocytomas, p = 0.014 in oligodendrogliomas) when adjusted for histological subtype. Residual disease after surgery (or biopsy) negatively affected survival (HR: 2.151, 95% CI: 1.375–3.367, P = 0.001). Post-surgical treatment with radiotherapy + adjuvant chemotherapy improved survival compared with follow-up and other treatments (HR: 0.316, 95% CI: 0.156–0.641, P = 0.001). Conclusions: In our study, histopathological grade still affects survival in IDH-mutant WHO grade II and III diffuse gliomas. This effect appears to be independent from molecular features, extension of surgical resection and post-surgical treatments. Therefore, physicians should continue to take into account tumour grade, along their molecular characteristics, for a better clinical and therapeutic management of the patients.

Background. Stimulated thyroglobulin levels measured at the time of remnant ablation (A-hTg) and BRAFV600E mutation had shown prognostic value in predicting persistent disease in differentiated thyroid cancer (DTC). The aim of this study was to evaluate the prognostic role of A-hTg combined with the BRAFV600E status in association with the revised American Thyroid Association (ATA) risk stratification. Material and Methods. 620 patients treated for a DTC were included in this study with a median follow-up duration of 6.1 years. All patients underwent total thyroidectomy followed by radioiodine ablation. Patients with positive anti-thyroglobulin antibodies were excluded. The predictive value of A-hTg was calculated by receiver operating characteristic curve (ROC curve) analysis. The Cox proportional hazard regression model, including the BRAF status, A-hTg, and ATA classification system, was assessed to evaluate the existing persistent disease risk. Results. Taken together, the BRAF status and A-hTg levels improve the ATA risk classification in all categories. In particular, in the low-risk ATA classification, only the combination of BRAFV600E+A-hTg>8.9ng/ml was associated with persistent disease (P=0.001, HR 60.2, CI 95% 5.28-687). In the intermediate-risk ATA classification, BRAFWT+A-hTg>8.9ng/ml was associated with persistent disease (P=0.029, HR 2.71, CI 95% 1.106-6.670) and BRAFV600E+A-hTg>8.9ng/ml was also associated with persistent disease (P<0.001, HR 5.001, CI 95% 2.318-10.790). In the high-risk ATA classification, both BRAFV600E+A-hTg<8.9ng/ml and BRAFV600E+A-hTg>8.9 ng/ml were associated with persistent disease (P=0.042, HR 5.963, CI 95% 1.069-33.255 and P=0.002, HR 11.564, CI 95% 2.543-52.576, respectively). Conclusions. The BRAF status and stimulated thyroglobulin levels at ablation time improve the ATA risk stratification of differentiated thyroid cancer; therefore, even A-hTg could be included in risk classification factors.

Aim: European Organization for Research and Treatment of Cancer (EORTC) and the Radiation Therapy Oncology Group (RTOG) criteria are used to choose treatment in low-grade gliomas. However, no data exist on their concordance. Methods: Low-grade glioma patients treated at our institution from 1998 to 2015 and assessable for both RTOG and EORTC criteria were included to analyze their concordance. Surgery extension, postsurgical treatments, molecular characteristics ( IDH mutation, MGMT methylation and 1p/19q codeletion) were recorded. Results: We included 99 patients. The concordance was low (50.5%; K = 0.127; p = 0.021) but for two subgroups: EORTC high-risk patients were also RTOG high-risk patients (concordance: 97.5%) and RTOG low-risk patients were also EORTC low-risk patients (concordance: 90.9%). Conclusion: The concordance between RTOG and EORTC criteria is low. Thus, clinical trials adopting different risk criteria are not comparable.

The standard treatment in children with average-risk medulloblastoma (MB) is reduced-dose radiotherapy (RT) followed by chemotherapy. However, in adults, there is no agreement on the use of adjuvant chemotherapy. We performed a retrospective analysis of adult MB patients with average-risk disease, defined as no postsurgical residual (or ≤1.5 cm(2)) and no metastatic disease (M0). Main inclusion criteria were: age16 years, post-surgical treatment with craniospinal irradiation with or without adjuvant chemotherapy (cisplatin and etoposide ± cyclophosphamide). From 1988 to 2012 were accrued 43 average-risk MB patients treated with surgery and adjuvant RT. Fifteen (34.9 %) patients received also chemotherapy: 7 before RT, 5 after RT, and 3 before and after RT. Reasons to administer chemotherapy were presence of residual disease (even if ≤1.5 cm) and delay in RT. After a median follow up time of 10 years (range: 8-13), median survival was 18 years (95 % CI 9-28) in patients who receive RT alone, and was not reached in patients treated with RT plus chemotherapy. The survival rates at 5, 10 and 15 years were 100 %, 78.6 % (95 % CI 60.0-97.2 %) and 60.2 % (95 % CI 36.9-83.5 %), in patients treated with RT alone, and 100, 100 and 100 %, in patients treated with RT plus chemotherapy (p = 0.079). Our findings suggest a role for adjuvant chemotherapy in the treatment of average-risk MB adult patients. Further improvements might drive to add chemotherapy in average-risk setting with less favourable biological signatures (i.e., non-WNT group).

Background: Clinical and molecular factors are essential to define the prognosis in patients with glioblastoma (GBM). O6-methylguanine-DNA methyltransferase (MGMT) methylation status, age, Karnofsky Performance Status (KPS), and extent of surgical resection are the most relevant prognostic factors. Our investigation of the role of gender in predicting prognosis shows a slight survival advantage for female patients. Methods: We performed a prospective evaluation of the Project of Emilia Romagna on Neuro-Oncology (PERNO) registry to identify prognostic factors in patients with GBM who received standard treatment. Results: A total of 169 patients (99 males [58.6%] and 70 females [41.4%]) were evaluated prospectively. MGMT methylation was evaluable in 140 patients. Among the male patients, 36 were MGMT methylated (25.7%) and 47 were unmethylated (33.6%); among the female patients, 32 were methylated (22.9%) and 25 were unmethylated (17.9%). Survival was longer in the methylated females compared with the methylated males (P = 0.028) but was not significantly different between the unmethylated females and the unmethylated males (P = 0.395). In multivariate analysis, gender and MGMT methylation status considered together (methylated females vs. methylated males; hazard ratio [HR], 0.459; 95% confidence interval [CI], 0.242-0.827; P = 0.017), age (HR, 1.025; 95% CI, 1.002-1.049; P = 0.032), and KPS (HR, 0.965; 95% CI, 0.948-0.982; P < 0.001) were significantly correlated with survival. Conclusions: Survival was consistently longer among MGMT methylated females compared with males. Gender can be considered as a further prognostic factor.

none 14 no Aim: To identify patients with recurrent glioblastoma after temozolomide (TMZ) concurrent with and adjuvant to radiotherapy who could benefit from TMZ rechallenge at the time of disease progression. Methods: We retrospectively evaluated 106 glioblastoma patients who had nonprogressive disease at first magnetic resonance imaging after completion of TMZ concurrent with and adjuvant to radiotherapy, a treatment-free interval (TFI) of at least 8 weeks and received TMZ rechallenge or a nitrosourea at the time of progression. Results: In patients with TFI ≥5 months, median survival was 17.7 and 11.6 months and median progression-free survival was 8.1 and 5.8 months in the TMZ and nitrosourea group, respectively. Longer TFI was associated with reduced risk for death (p = 0.002) and for disease progression (p = 0.005). Conclusion: TFI ≥5 months represents a predictor of retained TMZ sensitivity. none Franceschi, Enrico; Lamberti, Giuseppe; Visani, Michela; Paccapelo, Alexandro; Mura, Antonella; Tallini, Giovanni; Pession, Annalisa; De Biase, Dario; Minichillo, Santino; Tosoni, Alicia; Di Battista, Monica; Cubeddu, Alessio; Bartolini, Stefania; Brandes, Alba A* Franceschi, Enrico; Lamberti, Giuseppe; Visani, Michela; Paccapelo, Alexandro; Mura, Antonella; Tallini, Giovanni; Pession, Annalisa; De Biase, Dario; Minichillo, Santino; Tosoni, Alicia; Di Battista, Monica; Cubeddu, Alessio; Bartolini, Stefania; Brandes, Alba A*

Standard glioblastoma therapy is long-lasting. Among second-line therapy, choices could be bevacizumab and nitrosoureas depending on National Agencies approval. There is no consensus on 3rd line therapy or clinical trials specifically designed for this setting. We reviewed our institutional database on all consecutive patients who received 3rd line therapy for glioblastoma. Data on 168 out of 1337 (12.6%) glioblastoma patients who underwent 3rd line therapy treatment were collected. Third line treatments were bevacizumab or chemotherapy (nitrosourea, temozolomide or carboplatin plus etoposide). Median progression free survival was 2.9 months and median survival time was 6.6 months from the start of 3rd line therapy. Bevacizumab significantly improved progression-free survival (4.7 vs. 2.6 months, p = .020) and survival from 3rd line start (8.0 vs. 6.0 months, p = .014) in respect to chemotherapy. Toxicity of grade ≥ 3 occurred in 13.7% of patients. In multivariate analysis, survival in 3rd line treatment depends on MGMT methylation (p = .006) and treatment with Bevacizumab (p = .011). Third line therapy in selected glioblastoma patients may be feasible and well tolerated. Bevacizumab improved outcome in 3rd line in respect to chemotherapy.

2037 Background: Medulloblastoma is extremely rare in adults and, therefore, it is difficult to accrual patients in clinical trials. Radical surgery and radiotherapy (RT) provide a significant control of disease. Nevertheless, about 25% of average-risk patients have a relapse and die because of disease progression. The role of chemotherapy (CT) after standard RT for average-risk adult patients remains controversial. Methods: We analyzed 48 average-risk patients according to Chang classification diagnosed from 1988 to 2016. Median age was 29 years (range 16-61), M/F ratio was 26 (54.2%)/22 (45.8%). Fifteen patients had classic medulloblastoma (31.3%), 15 patients had desmoplastic medulloblastoma (31.3%), 5 patients had extensive nodularity (10.4%) and 2 patients had large cells/anaplastic histology (4.2%). The patients were homogeneously distributed in the two groups: 24 (50%) received adjuvant RT alone and 24 (50%) received RT + CT that consisted in a platinum-etoposide based combination. Results: After a median follow-up of 12.5 years, CT increases progression-free survival rate at 15 years (PFS-15 82.3 ± 8.0% in RT-CT group vs. 38.5% ± 13.0% in RT group p = 0.05) and overall survival rate at 15 years (OS-15 89.3% 7.2% vs. 52.0% 13.1%, p = 0.02). Among patients receiving CT, the reported grade ≥ 3 adverse events were: 9 cases of neutropenia; 6 cases of G3 neutropenia (25%) and 3 cases of G4 neutropenia (13%), 1 case of G3 thrombocytopenia (4%) and 2 cases of G3 nausea (8%). Conclusions: Our study with a long follow up period suggests that adding adjuvant chemotherapy to RT might improve PFS and OS in average-risk adult medulloblastoma patients.

e14057Background: About 21-62% of GBM patients (pts) access to 3rd line therapy. In this setting, there is no defined standard. In this study we evaluated the outcome of pts who received 3rd line t...

2040Background: Low grade gliomas (LGG) are a heterogeneous group of brain primary tumors. The EORTC and the RTOG criteria are the most valuable scores to evaluate risk factors and for treatment de...

2017 Background: Molecular characterization of low grade gliomas (LGG) is essential for diagnosis and treatment of these diseases. LGG patients (pts) with IDH mutation and 1p19q codeletion (codel) are characterized by a median OS (mOS) longer than 10 years. Thus, the role of treatments and side effects should be carefully evaluated. Methods: We evaluated LGG pts from our data warehouse (n=679 pts) who received surgery and had sufficient tissue to assess biomarkers characterization. Pts with gliomatosis were excluded. IDH1/2 assessment was performed on formalin-fixed paraffin-embedded samples by qPCR. In wild type cases we performed NGS. 1p/19 codel analysis was performed by FISH. Results: 93 consecutive LGG with IDH mutation and codel were included. The median follow up (FU) was 96.1 months. Mean age was 40 yrs (range: 25-66); 8 pts (8.6%) underwent biopsy, 61 pts (65.6%) partial resection, 24 pts (25.8%) complete resection. 84 pts (90.3%) were considered high risk using RTOG criteria (>40 years and/or incomplete resection). Fifty pts (53.7%) received only FU, 17 pts (18.3%) received chemotherapy (CT), 18 pts (19.4%) received radiotherapy (RT), 8 pts (8.6%) received RT + CT. Median PFS (mPFS) was 59.6 months (95%CI: 41.8-77.4) and was significantly longer in pts who received postsurgical treatments (79.5 months, 95%CI: 66.4-92.7) than pts who received FU (46.3 months, 95%CI: 36.0-56.5; P=0.001). mPFS was 50.8 months (95%CI: 17.4-84.3), 103.6 months (95%CI: 11.7-195.6) and 120.2 months (95%CI: 40.5-199.8) in pts treated with CT alone, RT alone and RT + CT, respectively. Multivariate analysis showed that receiving a post-surgical treatment (P

Summary Background Incidental discovery of adrenal masses has increased over the past few years. Mild alterations in cortisol secretion without clinical signs of overt hypercortisolism (subclinical Cushing's syndrome) are a common finding in patients with these tumours. Although metabolic alterations and increased cardiovascular risk have been noted in patients with subclinical Cushing's syndrome, incidence of cardiovascular events and mortality in the long term have not been assessed. We aimed to ascertain the frequency of new cardiovascular events and mortality in patients with non-secreting adrenal incidentalomas, tumours of intermediate phenotype, or those causing subclinical Cushing's syndrome. Methods From January, 1995, to September, 2010, consecutive outpatients with adrenal incidentalomas who were referred to the endocrinology unit of S Orsola-Malpighi Hospital, Bologna, Italy, were enrolled into our study. Individuals were assessed every 18–30 months for the first 5 years (mean follow-up 7·5 [SD 3·2] years, range 26 months to 15 years). Cortisol concentrations after the 1 mg dexamethasone suppression test (DST) were used to define non-secreting (+50 nmol/L) and intermediate phenotype (50–138 nmol/L) adrenal incidentalomas and subclinical Cushing's syndrome (+138 nmol/L). At the end of follow-up, patients were reclassified as having either unchanged or worsened secreting patterns from baseline. Findings 198 outpatients were assessed; at the end of follow-up, 114 patients had stable non-secreting adrenal incidentalomas, 61 had either a stable intermediate phenotype or subclinical Cushing's syndrome, and 23 had a pattern of secretion that had worsened. By comparison with patients with stable non-secreting adrenal incidentalomas, the incidence of cardiovascular events was higher in individuals with a stable intermediate phenotype or subclinical Cushing's syndrome (6·7% vs 16·7%; p=0·04) and in those with worsened secreting patterns (6·7% vs 28·4%; p=0·02). Cardiovascular events were associated independently with a change (from baseline to the end of follow-up) in cortisol concentrations post DST (hazard ratio 1·13, 95% CI 1·05–1·21; p=0·001). Survival rates for all-cause mortality were lower in patients with either stable intermediate phenotype adrenal incidentalomas or subclinical Cushing's syndrome compared with those with stable non-secreting masses (57·0% vs 91·2%; p=0·005). Factors associated with mortality were age (hazard ratio 1·06, 95% CI 1·01–1·12; p=0·03) and mean concentrations of cortisol post DST (1·10, 1·01–1·19; p=0·04). Compared with patients with stable non-secreting adrenal incidentalomas, unadjusted survival for cardiovascular-specific mortality was lower in patients with either a stable intermediate phenotype or subclinical Cushing's syndrome (97·5% vs 78·4%; p=0·02) and in those with worsened secreting patterns (97·5% vs 60·0%; p=0·01). Cancer mortality did not differ between groups. Interpretation Even when clinical signs of overt hypercortisolism are not present, patients with adrenal incidentalomas and mild hypercortisolism have an increased risk of cardiovascular events and mortality. Funding None.

Cough is a frequent symptom associated to upper respiratory tract infections (URTIs) and, although being self-limiting, it might deeply affect the quality of life. Homeopathic products are often employed by patients to treat cough, but the evidence on their efficacy is scarce. Thus, we tested the efficacy of a homeopathic syrup in treating cough arising from URTIs with a randomized, double blind, placebo controlled clinical trial. Patients were treated with either the homeopathic syrup or a placebo for a week, and recorded cough severity in a diary by means of a verbal category-descriptive score for two weeks. Sputum viscosity was assessed with a viscosimeter before and after 4 days of treatment; patients were also asked to provide a subjective evaluation of viscosity. Eighty patients were randomized to receive placebo (n = 40) or the homeopathic syrup (n = 40). All patients completed the study. In each group cough scores decreased over time, however, after 4 and 7 days of treatment, cough severity was significantly lower in the homeopathic group than in the placebo one (p < 0.001 and p = 0.023, respectively). Sputum was collected from 53 patients: in both groups its viscosity significantly decreased after 4 days of treatment (p < 0.001); however, viscosity was significantly lower in the homeopathic group (p = 0.018). Instead, the subjective evaluation did not significantly differ between the two groups (p = 0.059). No adverse events related to any treatment were reported. We concluded that the homeopathic syrup employed in the study was able to effectively reduce cough severity and sputum viscosity, thereby representing a valid remedy for the management of acute cough induced by URTIs.

Context: Physiological transient imbalance typical of adolescence needs to be distinguished from hyperandrogenism-related dysfunction. The accurate determination of circulating androgens is the best indicator of hyperandrogenism. However, reliable reference intervals for adolescent and young women are not available. Objective: The aim of the study was to define androgen reference intervals in young women and to analyze the impact of the menstrual phase and ovulation efficiency over the androgen profile as assessed by reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique. Participants: Female high school students aged 16-19 years were included in the study. Main Outcome Measures: The study was performed on reference subjects properly selected among an unbiased population. Normal-weight, drug and disease free, eumenorrheic females with no signs of hyperandrogenism were included. The steroid hormone profile was determined by a validated in-house LC-MS/MS method. A statistical estimation of overall and menstrual phase-specific reference intervals was performed. A subgroup of anovulatory females was identified based on progesterone circulating levels. The impact of ovulation efficiency over hormonal profile was analyzed. Results: A total of 159 females satisfied healthy criteria. Androgen levels did not vary according to menstrual phase, but a significantly higher upper reference limit was found for T in the luteal phase compared to the follicular phase. Higher T and androstenedione levels were observed in anovulatory compared to ovulatory females, paralleled by higher LH and FSH and lower 17-hydroxy-progesterone and 17 beta-estradiol levels. Conclusions: This is the first study providing LC-MS/MS-based, menstrual phase-specific reference intervals for the circulating androgen profile in young females. We identified a subgroup of anovulatory healthy females characterized by androgen imbalance.

2047 Background: The treatment of recurrent glioblastoma (GBM) remains an open issue, and the role of bevacizumab (BEV) has been widely debated since a few studies compared this agent with the stan...