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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.

Introduction: The aim of this multicenter comparison of balloon-occluded transarterial chemoembolization (B-TACE) versus conventional TACE (cTACE) in treating hepatocellular carcinoma (HCC) was to assess in which size range the 2 techniques offered higher complete response (CR) and objective response (OR) rates in a single session, and to evaluate the possibility of using B-TACE to reduce the need for re-treatment. Methods: 325 patients were retrospectively evaluated: 91 patients in the B-TACE group (22 with cTACE [B-cTACE] and 69 with drug-eluting microsphere TACE [B-DEM-TACE]) and 234 in the cTACE group. The results were compared according to tumor size: (A) 50 mm; OR and CR rates after the first session and the number of TACE re-interventions within a 6-month period were also evaluated using propensity score matching (PSM). Results: The best target ORs were very high (93.2%) and similar between the 2 treatments both before (94.4% for cTACE and 90.1% for B-TACE) and after PSM (94.5% for cTACE and 90.1%; p = 0.405), with slightly better results for the cTACE cohort probably due to better cTACE effectiveness in smaller lesions. In lesions 50 mm), cTACE and B-TACE performed equally, with a poor CR rate (22.6 vs. 23.1%, respectively; p = 1.000). These results were additionally confirmed using PSM. The patients treated with B-TACE had a significantly lower re-treatment rate than the cTACE cohort (12.1 vs. 26.9%, respectively; p = 0.005). B-cTACE and B-DEM-TACE demonstrated similar ORs, with a slightly better CR rate for B-cTACE (68.2 vs. 56.5%, respectively; p = 0.456). Conclusion: In HCCs of 30-50 mm, B-TACE should be preferred to cTACE, whereas in smaller nodules (, SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Bile leak (BL) after hepato-pancreato-biliary (HPB) surgery is associated with significant morbidity and mortality. Aim of this study was to evaluate effectiveness and safety of percutaneous transhepatic approach (PTA) to drainage BL after HPB surgery. Methods: Between 2006 and 2018, consecutive patients who were referred to interventional radiology units of three tertiary referral hospitals were retrospectively identified. Technical success and clinical success were analyzed and evaluated according to surgery type, BL-site and grade, catheter size and biochemical variables. Complications of PTA were reported. Results: One-hundred-eighty-five patients underwent PTA for BL. Technical success was 100%. Clinical success was 78% with a median (range) resolution time of 21 (5–221) days. Increased clinical success was associated with patients who underwent hepaticresection (86%,p = 0,168) or cholecystectomy (86%,p = 0,112) while low success rate was associated to liver-transplantation (56%,p < 0,001). BL-site,grade, catheter size and AST/ALT levels were not associated with clinical success. ALT/AST high levels were correlated to short time resolution (17 vs 25 days, p = 0,037 and 16 vs 25 day, p = 0,011, respectively) Complications of PTA were documented in 21 (11%) patients. Conclusion: This study based on a large cohort of patients demonstrated that PTA is a valid and safe approach in BL treatment after HPB surgery.

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.

Purpose: To evaluate the diagnostic accuracy of the four standardized categories for CT reporting proposed by the Radiological Society of North America (RSNA) to support a faster triage compared with real-time reverse-transcription polymerase chain reaction (RTPCR), which is the reference standard for suspected coronavirus disease 2019 (COVID-19), but has long reporting time (6–48 hours). Materials and Methods: A retrospective analysis of 569 thin-section CT examinations performed for patients suspected of having COVID-19 from February 27 to March 27, 2020 (peak of infection in Italy) was conducted. The imaging pattern was classified according to the statement by the RSNA as “typical,” “indeterminate,” “atypical,” and “negative” and compared with RT-PCR for 460 patients. Interobserver variability in reporting between a senior and a junior radiologist was evaluated. Use of the vascular enlargement sign in indeterminate cases was also assessed. Results: The diagnosis of COVID-19 was made in 45.9% (211/460) of patients. The “typical” pattern (n = 172) showed a sensitivity of 71.6%, a specificity of 91.6%, and a positive predictive value of 87.8% for COVID-19. The “atypical” (n = 67) and “negative” (n =123) pattern demonstrated a positive predictive value of 89.6% and 86.2% for non–COVID-19, respectively. The “indeterminate” (n = 98) pattern was nonspecific, but vascular enlargement was most frequently found in patients with COVID-19 (86.1%; P , .001). Interobserver agreement was good for the “typical” and “negative” pattern and fair for “indeterminate” and “atypical” (k = 0.5; P =.002). Conclusion: In an epidemic setting, the application of the four categories proposed by the RSNA provides a standardized diagnostic hypothesis, strongly linked to the RT-PCR results for the “typical,” “atypical,” and “negative” pattern. In the “indeterminate” pattern, the analysis of the vascular enlargement sign could facilitate the interpretation of imaging features.

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

According to the 2016 World Health Organization (WHO) classification of tumors of the central nervous system, assessment of exon 4 mutations in isocitrate dehydrogenase 1 or 2 genes (IDH1 or IDH2) is an essential step in the characterization of gliomas. The p.R132H mutation is the most frequent alteration in IDH genes, however other non-canonical IDH mutations can be identified. The aim of this study is to investigate in depth the prevalence of non-R132H IDH ("non-canonical") mutations in brain tumors classified according to the 2016 WHO scheme and their clonal distribution in neoplastic cells. A total of 288 consecutive cases of brain gliomas (grade II-IV) were analyzed for exon 4 IDH1 and IDH2 mutations. IDH1 and IDH2 analysis was performed using next generation sequencing. Non-canonical IDH mutations were identified in 13/52 (25.0%) grade II gliomas (astrocytomas: 8/31, 25.8%; oligodendrogliomas: 5/21, 23.8%) and in 5/40 (12.5%) grade III gliomas (astrocytomas: 3/25, 12.0%; oligodendrogliomas: 2/15, 13.3%). They were not identified in 196 grade IV gliomas (192 glioblastomas, 4 gliosarcomas). In the large majority (>80%) of tumors IDH mutations, both IDH1-R132H and the non-canonical ones, were present in the large majority (>80%) of neoplastic cells. Our data highlight the importance of investigating not only the IDH1-R132H mutation but also the non-canonical ones. These mutations are clonally distributed, with proportions of mutated neoplastic cells overlapping with those of p.R132H, a finding consistent with their driver role in gliomagenesis.

// 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).

2523 Background: Anaplastic gliomas are classified according to the presence of IDH-mutation. IDH wild type (IDH wt) is associated with poor prognosis and limited effectiveness of treatments.The aim of this study was to find out if MGMT methylation represents a prognostic factor in this setting. Methods: Anaplastic gliomas are classified according to the presence of IDH-mutation. IDH wild type (IDH wt) is associated with poor prognosis and limited effectiveness of treatments.The aim of this study was to find out if MGMT methylation represents a prognostic factor in this setting. Results: The analysis included 73 pts with grade III, IDH wt (19.3%) gliomas. Median follow-up time was 69.9 months. Median age was 50 (Range: 18-75), M/F ratio was 40(54.8%)/33(45.2%).MGMT promoter was methylated in 34 pts (46.6%) and unmethylated in 39 pts (53.4%). After surgery, 9 pts (12.3%) received RT alone, 57 pts (78.1%) received both RT and CT (sequential, concomitant or both). Median survival was 26.2 months. In multivariate analysis age (HR = 1.064, 95%CI: 1.030-1.099; P < 0.001) and MGMT methylation (HR = 0.422, 95%CI: 0.210-0.848; P = 0.015) were independently associated with risk for death. Conclusions: IDH wild type confers a dismal prognosis in patients with grade III gliomas. MGMT methylation, as was demonstrated in glioblastoma, represents a prognostic factor that correlated with lower risk for death. Further studies will investigate potential correlations with treatments.

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.

Background Epidermal Growth Factor Receptor (EGFR) molecular analysis is performed to assess the responsiveness to Tyrosine Kinase Inhibitors (TKIs) in patients with Non-Small Cell Lung Cancer (NSCLC). The existence of molecular intra-tumoral heterogeneity has been observed in lung cancers. The aim of the present study is to investigate if the percentage of mutated neoplastic cells within the tumor sample might influence the responsiveness to TKIs treatment. Material and methods A total of 931 cases of NSCLC were analyzed for EGFR mutational status (exon 18, 19, 20, 21) using Next Generation Sequencer. The percentage of mutated neoplastic cells was calculated after normalizing the percentage of mutated alleles obtained after next generation sequencer analysis with the percentage of neoplastic cells in each tumor. Results Next generation sequencing revealed an EGFR mutation in 167 samples (17.9%), mainly deletions in exon 19. In 18 patients treated with TKIs and with available follow-up, there was a significant correlation between the percentage of mutated neoplastic cells and the clinical response (P = 0.017). Patients with a percentage of mutated neoplastic cells greater than 56%, have a statistical trend (P = 0.081) for higher Overall Survival (26.3 months) when compared to those with a rate of mutated neoplastic cells lower than 56% (8.2 months). Conclusions The percentage of EGFR-mutated neoplastic cells in the tumor is associated with response to TKIs. A “quantitative result” of EGFR mutational status might provide useful information in order to recognize those patients which might have the greatest benefit from TKIs.

Background & Aims Acute infectious gastroenteritis increases the risk for irritable bowel syndrome (IBS) and functional dyspepsia (FD). Children are particularly vulnerable to gastroenteritis because of the immaturity of their intestinal barrier, enteric nervous system, and immune response to pathogens. We investigated whether acute gastroenteritis in early life increases the risk of IBS and FD throughout adulthood. Methods In 1994, we identified and monitored a single culture-proven foodborne Salmonella enteritidis outbreak that involved 1811 patients (mostly pediatric) in Bologna, Italy. Clinical data were collected and a prospective, controlled, cohort study was designed. Long-term effects were assessed by mailing a questionnaire to 757 subjects 16 years after the outbreak (when all of the children were adults). We randomly selected a cohort of 250 adults exposed to Salmonella as children, all 127 individuals exposed as adults, and a cohort of nonexposed participants matched for number, age, sex, and area of residence (controls). Results Among 198 exposed participants, 64 reported FD (32.3%), compared with 51 of 188 controls (27.1%; P = .268). Among 204 exposed participants, 75 reported having IBS (36.8%) compared with 44 of 189 controls (23.3%; P = .004). The odds ratio for IBS among people exposed to the Salmonella was 1.92 (95% confidence interval: 1.23–2.98). The prevalence of IBS was higher in individuals exposed Salmonella as children than in controls (35.3% vs 20.5%; P = .008), but not in individuals exposed as adults, compared with controls. After multivariate logistic regression, post-infectious IBS was independently associated with anxiety and FD. Conclusions Based on data collected from a single culture-proven foodborne Salmonella enteritidis outbreak in 1994, Salmonella -induced gastroenteritis during childhood (but not adulthood) is a risk factor for IBS.

Objectives To assess the intermethod agreement between two-dimensional (2D) and three-dimensional (3D) transperineal ultrasound methods in measuring a new index of fetal head station (the fetal head–symphysis distance (HSD)) in active labor, and to assess potential factors that may affect their agreement. Methods HSD was measured by transperineal ultrasound in 86 women in active labor, once using a 2D and once using a 3D technique. 2D images were acquired first in 43 cases and 3D images were acquired first in the other 43 women. Intermethod agreement between 2D and 3D methods was analyzed by means of intraclass correlation coefficient (ICC) and Bland–Altman analysis. In addition, potential factors affecting the intermethod reproducibility were investigated including fetal occiput position, order of acquisition, fetal head station, stage of labor, maternal body mass index and use of epidural analgesia, using the ANOVA test to check for systematic bias and Levene's test for homoscedasticity. Results Good agreement was demonstrated between 2D and 3D measurements of HSD (ICC, 0.949 (95% CI, 0.914–0.984)). No evidence of systematic difference was shown between the two methods (average difference ± SD = 0.03 ± 2.29 mm; P = 0.888). The only factor that had a significant effect on systematic difference between 2D and 3D methods was order of acquisition (P = 0.042); the first observation was higher regardless of the method used. Fetal head station had a significant effect on the homogeneity between the two methods (P = 0.004) with a better 2D–3D agreement obtained at lower head stations (SD of differences: 1.63 vs 2.59 mm). Conclusions There is very good agreement between 2D and 3D methods of assessing HSD. Agreement is better in lower fetal head stations. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

2028 Background: According to the 2016 WHO classification of Central Nervous System tumors, the assessment of exon 4 mutations in IDH1 or IDH2 genes is an essential step in the characterization of gliomas. The R132H mutation is the most frequent alteration in IDH1 gene, however other non-canonical IDH mutations have been identified. The aim of this study was to evaluate the prognostic role of IDH non-canonical mutations. Methods: We analyzed our institutional data warehouse for all consecutive patients (pts) with newly diagnosed, histologically proven grade II – IV IDH mutant gliomas. IDH sequencing was performed using the 454 GS-Junior next generation sequencer (NGS) (Roche Diagnostic, Mannheim, Germany). All analyses were performed on DNA from formalin fixed and paraffin embedded (FFPE) specimens. Results: The analysis included 493 pts with IDH mutations. We found 279 (56.6%) grade 2, 173 grade 3 (35.1%) gliomas, and 41 (8.3%) IDH mutant glioblastoma. Canonical IDH1 R132H mutation was found in 428 pts (86.8%). The remaining pts showed IDH2 (3.9%) or IDH 1 non-canonical mutations (mainly R132C, R132G, R132S – 9.3%). Median follow-up time was 80.5 months. Pts with non-canonical mutations showed a younger median age (32 vs 39 years, p < 0.001). Other clinical characteristics and treatments were similar across IDH groups. Median survival was 145 months (95%CI: 137.7 - 152.9) and 198.6 (95%CI 155.2– 242.1) in patients with IDH R132H and non-canonical mutations, respectively (p = 0.013). In multivariate analysis grading (p < 0.001), extent of surgery (p < 0.001), 1p19q codeletion (p = 0.003) and presence of non-canonical mutations (p = 0.022) showed a significant role for improved survival. Conclusions: Detecting non-canonical IDH1 mutations is essential for diagnosis and for prognosis in patients with gliomas. Differential enzymatic activity of non-canonical IDH1 mutations, resulting in different levels 2-hydroxyglutaratecould be the reason of improved survival.

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.

2036 Background: The 2016 WHO classification dramatically changed the diagnosis of gliomas. Diffuse gliomas are classified according to the presence of IDH-mutation (IDH-mut) and the deletion of both 1p and 19q chromosome arms (1p/19q codel). Now debate is whether grade still has an independent prognostic value. The aim of this study was to find out if grade is a prognostic factor independently of molecular status. Methods: We analyzed our institutional data warehouse for all consecutive patients (pts) with newly diagnosed, histologically proven Grade II or Grade III IDH-mut gliomas. IDH 1/2 assessment by polymerase chain reaction (PCR)or immunohistochemistry (IHC) was accepted. Next Generation Sequencing (NGS) for IDH1(exon 4) and IDH2(exon 4) was performed on all specimens wild-type for the IDH. Results: The analysis included all the 399 pts who had a grade II (n = 250, 62.7%) or grade III (n = 149, 37.3%). Median follow-up time was 105.3 months. After surgery, 72 pts (18.0%) received RT alone, 44 (11.0%) received CT alone, 135 (33.8%) received both RT and CT, and 142 (35.6%) follow-up without any treatment. Median survival was 148.1 months. In multivariate analysis Grade (HR = 0.342, 95%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 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 RT + adjuvant CT improves survival in respect to follow-up and other treatments (HR: 0.316, 95%CI 0.156 – 0.641, P = 0.001). Conclusions: Grade still affects survival in IDH mutant Grade II and III gliomas. This effect was independent onmolecular features, surgical extension and post-surgical treatments. Clinical management of gliomas should continue to take into account grade as well as molecular characteristics.

e14734 Background: IDH mutational status is required for diagnosis according to the 2016 WHO criteria. The single nucleotide polymorphism (SNP) rs11554137 ( IDH1105GGT) at codon 105 of IDH1 has been reported in patients with several tumor types, including glioma. The aim of this study is to investigate the prognostic role of IDH1105GGT Methods: We analyzed our institutional data warehouse for consecutive patients (pts) with newly diagnosed, histologically proven grade II or Grade III gliomas. IDH sequencing was performed using the 454 GS-Junior next generation sequencer (NGS) (Roche Diagnostic, Mannheim, Germany). All analyses were performed on DNA from formalin fixed and paraffin embedded (FFPE) specimens. Results: The analysis included 77 pts with grade II (n = 51, 66.2%) or grade III glioma (n = 26, 33.8%). Median follow up of this study was 91 months. Patients received biopsy/partial resection/complete resection in 7.8%, 70.1% and 22.1%, respectively. Postsurgical RT and/or chemotherapy was delivered in 64.9% of pts. IDH mutations affecting codons 132 (for IDH1) and 172 (for IDH2) were found in 71 pts (92.2%). IDH1105GGTwas found in 11 pts (14.3%), mainly harboring also IDH mutations (81.8%), and was more frequent in grade 3 (30.8%) than in grade 2 gliomas (5.9%, P = 0.006). Pts harboring both IDH mutations and IDH1105GGTshowed a significantly longer progression-free survival compared with pts with IDH mutation alone (78.7 months vs 49.9 months, p = 0.041). Conclusions: IDH1105GGT represents a promising novel biomarker in IDH mutated grade 2 and 3 gliomas and warrants further investigations.

Purpose To investigate the effect of a low-dose oral contraceptive containing drospirenone/ethinylestradiol 3 mg/20 μg on endometrioma mean diameter. Methods Fifty women with sonographic diagnosis of ovarian endometrioma and at least 12 months of therapy with drospirenone/ethinylestradiol 3 mg/20 μg, without previous adnexal surgery, were selected for this retrospective study. Endometrioma mean diameter measured with transvaginal ultrasonography and endometriosis-associated symptoms evaluated by a visual analogue scale (VAS) score (0-10) were reported at therapy prescription (baseline) and after 6, 12 and 18 months of treatment. Main outcome measures were endometrioma mean diameters and endometriosis-associated symptoms variations during the follow-up; differences between cyclic and continuous regimen were also considered. Results A significant reduction in endometrioma mean diameter was observed during the follow-up. The reductions of mean diameter versus baseline values were significantly higher in continuous users than in cyclic users at 6 and 18 months of follow-up. No new endometriomas occurred. The dysmenorrhea VAS score significantly decreased during the follow-up. Conclusions Drospirenone/ethinylestradiol 3 mg/20 μg seems to be effective in reducing endometrioma mean diameter. The continuous regimen seems to be associated with a greater reduction than the cyclic one.

Objective To compare longitudinal changes in angle of progression (AoP) and midline angle (MLA) during the active second stage of labor according to the mode of delivery. Methods A three-dimensional transperineal ultrasound volume was acquired in a series of nulliparous women at the beginning of the active second stage (T1) and every 20 min thereafter (T2, T3, T4, T5 and T6). Following delivery, all ultrasound volumes were analyzed and AoP and MLA were measured. Results Among 71 women included in the study, 58 underwent spontaneous vaginal delivery (Group A) and 13 underwent operative delivery (Group B) (eight by vacuum extraction and five by Cesarean section). When compared with Group B, Group A had a wider AoP only at T1 (140.0 ± 20.2° vs 122.9 ± 16.7°; P = 0.010) and T2 (149.7 ± 20.7° vs 126.9 ± 17.5°; P = 0.006). MLA was narrower in Group A only at T3 (21.2 ± 11.7° vs 40.8 ± 27.9°; P = 0.043), T4 (18.2 ± 15.0° vs 47.4 ± 29.6°; P = 0.020) and T5 (18.3 ± 6.0° vs 34.7 ± 4.2°; P = 0.034). On stepwise forward multiple logistic regression analysis, both AoP and MLA were independently associated with operative delivery (OR = 0.955 and OR = 1.018, respectively). Conclusion Ultrasonographic assessment of fetal head descent in the second stage of labor may play a role in the prediction of the mode of delivery. Copyright © 2013 ISUOG. Published by John Wiley & Sons, Ltd.

Objectives To assess the reproducibility of measurement of a new sonographic index of fetal head station in labor, the fetal head–symphysis distance (HSD), using three-dimensional ultrasound, and its correlation with digital assessment of fetal head descent and with the angle of progression (AoP). Methods Three-dimensional (3D) ultrasound volumes were acquired from 47 nulliparous women in active labor following assessment of fetal head station with digital examination. The HSD (the distance between the lower edge of the pubic symphysis and the nearest point of the fetal skull) was measured independently by two operators in order to evaluate intra- and interobserver reproducibility. The correlation between HSD, AoP and fetal head station was evaluated using regression analysis. Using 3D tomographic ultrasound imaging (TUI), measurements of the HSD were obtained in different parasagittal planes to evaluate the influence of inaccurate alignment of the probe with the midline of the pelvis. Results Measurement of HSD showed high intraobserver (intraclass correlation coefficient (ICC) = 0.995; 95% CI, 0.991–0.997) and interobserver (ICC = 0.991; 95% CI, 0.984–0.995) reliability. In addition, a high correlation was demonstrated between mid-sagittal and parasagittal HSD measurements. HSD showed significant negative correlation with both fetal head station and AoP. Conclusion Fetal HSD is a simple and reliable method for the assessment of fetal head descent in labor. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

We included patients who received temozolomide concurrent with and adjuvant to radiotherapy after diagnosis of GBM and had a second surgery performed at least 3 months after radiotherapy completion. Other eligibility criteria were age ≥18 years and Eastern Cooperative Oncology Group performance status 0-2. We evaluated theFrom our institutional data warehouse, 295 patients with recurrent GBM who underwent second surgery were evaluated.

Background: The most appropriate management of recurrent glioblastoma is still controversial. In particular, the role of surgery at recurrence remains uncertain. Patients & methods: From our Institutional data warehouse we analyzed 270 consecutive patients who received second surgery for recurrent glioblastoma, to assess survival after second surgery, and to evaluate prognostic factors. Results: Complete resection was found in 128 (47.4%) and partial resection in 142 patients (52.6%). Median survival from second surgery was 11.4 months (95% CI: 10.0–12.7). Multivariate analysis showed that age (p = 0.001), MGMT methylation (p = 0.021) and extent of surgery (p < 0.001) are associated with better survival. Conclusion: A complete resection should be the goal for second resection and younger age and MGMT methylation status might be considered in the selection of 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...