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Background: Information about the adherence to scientific societies guidelines in the ‘real-world’ therapeutic management of oncological patients are lacking. This multicenter, prospective survey was aimed to improve the knowledge relative to 2017-2018 recommendations of the Italian Association of Medical Oncology (AIOM). Patients and methods: Treatment-naive adult patients with pancreatic adenocarcinoma were enrolled. Group A received adjuvant therapy, group B received primary chemotherapy, and group C had metastatic disease. The results on patients accrued until 31 October 2019 with a mature follow-up were presented. Results: Since July 2017, 833 eligible patients of 923 (90%) were enrolled in 44 Italian centers. The median age was 69 years (range 36-89 years; 24% >75 years); 48% were female; 93% had Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1; group A: 16%, group B: 30%; group C: 54%; 72% Nord, 13% Center, 15% South. In group A, guidelines adherence was 68% [95% confidence interval (CI) 59% to 76%]; 53% of patients received gemcitabine and 15% gemcitabine þ capecitabine; median CA19.9 was 29 (range 0-7300; not reported 15%); median survival was 36.4 months (95% CI 27.5-47.3 months). In group B, guidelines adherence was 96% (95% CI 92% to 98%); 55% of patients received nab-paclitaxel þ gemcitabine, 27% FOLFIRINOX, 12% gemcitabine, and 3% clinical trial; median CA19.9 was 337 (range 0-20220; not reported 9%); median survival was 18.1 months (95% CI 15.6-19.9 months). In group C, guidelines adherence was 96% (95% CI 94% to 98%); 71% of patients received nabpaclitaxel þ gemcitabine, 16% gemcitabine, 8% FOLFIRINOX, and 4% clinical trial; liver and lung metastases were reported in 76% and 23% of patients, respectively; median CA19.9 value was 760 (range 0-1374500; not reported 9%); median survival was 10.0 months (95% CI 9.1-11.1 months). Conclusions: The GARIBALDI survey shows a very high rate of adherence to guidelines and survival outcome in line with the literature. CA19.9 testing should be enhanced; nutritional and psychological counseling represent an unmet need. Enrollment to assess adherence to updated AIOM guidelines is ongoing.

Second- or third-line treatment options for metastatic renal cell carcinoma (mRCC) have dramatically changed in the last few years. There are no criteria for the choice between nivolumab and cabozantinib, which both demonstrated overall survival (OS) gain in pivotal trials.We conducted an analysis of oncological outcomes in patients treated in the Veneto Region (Italy), studying different sequences of TKI-nivolumab-cabozantinib or TKI-cabozantinib-nivolumab in a publicly funded healthcare system.We conducted a retrospective, real-world analysis of all consecutive patients with mRCC treated with nivolumab or cabozantinib in 2017-2018 at 19 Oncology Units in the Veneto Region.We identified 170 patients, 73 % males, median age 68.4 years. All patients started second-line treatment, 59 % received a third-line therapy. Patients with NLR3 had a shorter OS (p0.0001). In the second-line treatment, nivolumab was administered to 108 patients (63 %), cabozantinib to 29 (17 %); in the third-line treatment nivolumab was administered to 42 patients (25 %), cabozantinib to 49 (29 %). Median OS and PFS in second line treatment were 28.4 and 6.6 months for nivolumab, 16.8 and 6.6 months for cabozantinib. Median OS and PFS in third-line treatment were 27 and 5.2 months for nivolumab, 16.6 and 7.5 months for cabozantinib. Median OS for nivolumabcabozantinib sequence versus cabozantinibnivolumab was 28.8 versus 19.9 months (p = 0.2); median PFS for both the sequences were similar at 5.7 months. A cost effectiveness per month of survival of the two sequences analysis was performed: the cost per month for the nivolumabcabozantinib sequence was 1738.60whereas the cost for the other one was €1624.80.In our real-world cohort, most patients received nivolumab as second-line treatment. Outcomes of single drugs are superimposable with those in the published literature. Both the sequences of nivolumab and cabozantinib appear to be viable, effective strategies from an OS and cost-effective perspective.

Background Real-world (RW) evidence on nivolumab in pretreated patients with non-small cell lung cancer (NSCLC) by matching data from administrative health flows (AHFs) and clinical records (CRs) may close the gap between pivotal trials and clinical practice. Methods This multicenter RW study aims at investigating median time to treatment discontinuation (mTTD), overall survival (mOS) of nivolumab in pretreated patients with NSCLC both from AHF and CR; clinical-pathological features predictive of early treatment discontinuation (etd), budget impact (BI), and cost-effectiveness analysis were investigated; mOS in patients receiving nivolumab and docetaxel was assessed. Results Overall, 237 patients with NSCLC treated with nivolumab were identified from AHFs; mTTD and mOS were 4.2 and 9.8 months, respectively; 141 (59%) received at least 6 treatment cycles, 96 (41%) received < 6 (etd). Median overall survival in patients with and without etd were 3.3 and 19.6 months, respectively (P < .0001). Higher number, longer duration, and higher cost of hospitalizations were observed in etd cases. Clinical records were available for 162 patients treated with nivolumab (cohort 1) and 83 with docetaxel (cohort 2). Median time to treatment discontinuation was 4.8 and 2.6 months, respectively (P < .0001); risk of death was significantly higher in cohort 2 or cohort 1 with etd compared with cohort 1 without etd (P < .0001). Predictors of etd were body mass index 1, neutrophile-to-lymphocyte ratio >2.91, and concomitant treatment with antibiotics and glucocorticoids. The incremental cost-effectiveness ratio of nivolumab was 3323.64 euros ($3757.37) in all patients and 2805.75 euros ($3171.47) for patients without etd. Finally, the BI gap (real-theoretical) was 857 188 euros ($969 050.18). Conclusion We defined predictors and prognostic-economic impact of nivolumab in etd patients.

Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting.We conducted a multicenter retrospective analysis in the Triveneto region of Italy.One hundred fifty-eight patients received radium 223 in our region. After a median follow-up of 9.5 months, 75 patients died. The median overall survival (OS) was 14.2 months, and the median progression-free survival (PFS) was 6.2 months. Seventy-one (45%) patients achieved progression as best response. Thirty-seven (23%) patients stopped the treatment early because of progression. Eastern Cooperative Oncology Group performance status was prognostic for OS (18.4 vs. 12.3 vs. 7.5 months; 0 vs. 1, P = .0062; 0 vs. 2, P = .0002), whereas previous prostatectomy or docetaxel exposure were not. A neutrophil to lymphocytes ratio ≥ 3 significantly impacted OS (18.1 vs. 9.7 months; P .001) and slightly impacted PFS (6.6 vs. 5.6 months; P = .05). Patients with a baseline alkaline phosphatase (ALP) value ≥ 220 U/L had worse OS and PFS (24.1 vs. 10.5 months; 7.2 vs. 5.5 months; P .001). Patients with changes in ALP value achieved better OS (P = .029) and PFS (P = .002). There was no difference according to the line of therapy (0 vs. ≥ 1; P = .490). The main grade 3/4 toxicities were anemia, asthenia, and thrombocytopenia.This large real-world report confirms comparable OS and PFS data when compared with the pivotal study, as well as the predictive role of ALP and neutrophil to lymphocytes ratio. The definition of the optimal position of radium 223 in the treatment of metastatic castration-resistant prostate cancer has still to be defined.

2549 Background: ICIs lead to durable response and a significant survival improvement in a limited number of advanced stage Mel and NSCLC pts. The identification of predictive circulating biomarkers could be a promising tool to optimize pts’ selection and outcome for ICIs treatment. Methods: This is a prospective real-world study enrolling advanced stage Mel and NSCLC pts referred to four Italian Centers and treated with ICIs. The primary endpoint is to verify the presence of an association between circulating cytokines (IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNFα, GM-CSF) and disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Pts undergo a blood collection, before every cycle for 6 cycles (T1-T6) and at tumor assessment till disease progression (PD) or for 2 years. Biomarker levels were assessed by Luminex xMAP based technology using R&D High Sensitivity kits. Each marker was categorized according to high and low levels by maximizing its discriminative ability, and the association with the outcome was tested in univariate and multiple analyses. Results: We report preliminary results on the T1-T2 blood samples from the first 78 enrolled pts (32 females/46 males; 43 Mel/35 NSCLC; median age 69 years). Serum IL-6, IL-8 and IL-10 were significantly higher at T1 and T2 in pts with PD (Kruskal-Wallis test). The median relative increase (RI) of IL-8 was 32% and 2% in pts with PD and disease control (DC), respectively (p = 0.0001). At multiple logistic analysis, IL-6 and IL-8 at T2 and the RI of IL-8 were independent factors predicting the probability of DC, with an overall accuracy of 83.8%. High levels of IL-6 and IL-8 at T2 were significantly associated with a low probability of DC (OR = 0.13, 95%CI: 0.03-0.52 and OR = 0.09, 95%CI: 0.02-0.37, respectively), and the RI showed a significantly lower probability of DC (OR = 0.14, 95%CI: 0.02-0.58). With a median follow-up of 10.6 months (m), mPFS and mOS were 5.8 m, 95%CI: 2.3-7.4 and 8.3 m, 95%CI: 4.0-13.8 for NSCLC; 6.9 m, 95%CI: 2.8-15.9 and 12.6 m, 95%CI: 4.7-NE for Mel pts, respectively. In the multiple Cox model, elevated IL-6 and IL-8 at T1 (HR = 3.03, 95%CI: 1.55-6.37, HR = 2.86, 95%CI: 1.46-5.63), elevated IL-10 at T2 (HR = 2.86, 95%CI: 1.39-5.94), and a RI of IL-8 (HR = 4.22, 95%CI: 1.85-11.21) remained significantly associated with a worse PFS. Higher levels of IL-6 (HR = 3.85, 95%CI: 1.13-20.0) and IL-8 (HR = 4.29, 95%CI: 1.98-9.83) at T2 and a RI of IL-8 (HR = 3.06, 95%CI: 1.43-6.72) remained significantly associated with a worse OS. Conclusions: High serum levels of IL-8 and IL-6 at T2 of ICI, combined with an increase of IL-8 from baseline, are strong predictors of PD, PFS, OS, in pts with advanced Mel and NSCLC. The role of the other cytokines tested, their time fluctuations and associations with clinical prognostic factors, gender, and immuno-related adverse events will be presented at the meeting.

e24015 Background: Colorectal cancer (CRC) is the second most frequent malignancy in patients (pts) aged 70. Elderly patients are often excluded by clinical trials; however, improvements in quality of life and comorbidities management led to expand the access to anticancer treatments irrespectively of age per se. Finding new tools to stratify vulnerability in elderly pts is crucial to guide clinicians in therapeutic decisions. G8 and timed up and go test (TUG) have been related to prognosis and functional decline in patients affected by several solid tumors. However, no studies focused on TUG and G8 prognostic value in CRC pts are available. In this study, we assessed the prognostic value of G8 and TUG in a cohort of real-life elderly pts with metastatic CRC (mCRC). Methods: GOLD was a multicentre, observational, prospective study in which pts aged 70 with mCRC and eligible to 1st line therapy were enrolled. G8 and TUG were performed at screening and at the first documented disease progression (PD). G8 cutoff was 14, as reported in literature; TUG8,5 sec (cutoff set with ROC curve using MedCalc software v 20.027). PFS and OS were described with Kaplan-Meyer curve. All analyzed variables were then compared with multivariate models. Primary endpoint of the study was to assess prognostic value of G8 in OS and PFS. Secondary endpoints were to assess prognostic value of TUG in OS and PFS. Results: Since Oct 2017 to Apr 2019, 109 pts were evaluated in 4 different Oncology Units in Veneto (IT); 4 were not eligible to anticancer treatments and where thus excluded. 105 pts were finally enrolled. Clinical, histological and molecular characteristics were well balanced between pts with G814 vs > 14, with the exception of RASmut, more represented in the G8 > 14 group (p = 0,0195). 39 (37%) pts were aged80; 46 (44%) had ECOG PS1; 55 (53%) had RASmut; 15 (15%) had BRAFmut. 81 (77%) had G814; 78 (75%) had TUG8,5. At a median follow up time of 41,2 months, median OS was 19,41 months (95%CI 15,46-23,19) and median PFS 8,78 months (95% CI 7,53-10,07). OS was longer in patients with G814 (HR 0,61; 95%CI 0,39-0,97; p= 0,0584) and TUG8,5 (HR 0,55; 95%CI 0,35- 0,86; p= 0,0201). PFS was not influenced by G8 (HR 0,86; 95%CI 0,55-1,34; p= 0,5125) nor by TUG (HR 0,71; 95%CI 0,47-1,08). G814 and TUG8,5 conferred better OS also in the subgroup of RASmut (respectively p= 0,0133 and p= 0,0088). Worse OS was observed in presence of > 1 metastatic site (HR = 1,71; 95%CI 1,11 to 2,64; p= 0,0161). At the multivariate analysis, G814 ( p= 0,0202) and single metastatic site ( p= 0,0200) were related to better OS; none of the analysed variables had effect on PFS. Conclusions: In our study G814 and TUG8,5 had prognostic value in OS, but not in PFS, in a real-life population of elderly pts affected by mCRC. G8 and single metastatic site involvement were related to better OS, irrespectively of other clinical, histological and molecular variables.

Aim: Recommendations for managing patients with nasopharyngeal carcinoma (NPC) in non-endemic areas are largely derived from studies conducted in endemic areas. We analysed the impact of treatment approaches on survival in non-endemic areas. Methods: In an international, multicentre, retrospective study, we analyse consecutive patients with NPC diagnosed between 2004 and 2017 in 36 hospitals from 11 countries. Treatment was categorised as non-intensive (NIT), including radiotherapy alone or concomitant chemoradiotherapy (cCRT), and intensive (IT) including cCRT preceded by and/or followed by chemotherapy (CT). The impact of IT on overall survival (OS) and disease-free survival (DFS) was adjusted for all the available potential confounders. Results: Overall, 1021 and 1113 patients were eligible for overall survival (OS) and disease-free survival (DFS) analyses, respectively; 501 and 554 with Epstein Barr-encoded RNA (EBER) status available. In the whole group, 5-year OS was 84% and DFS 65%. The use of NIT was associated with a risk of death or recurrence 1.37 times higher than patients receiving IT. Patients submitted to NIT and induction CT thorn concurrent concomitant chemo and three-dimensional Conformal Radiation Therapy (3DCRT) had a risk of death or recurrence 1.5 and 1.7 times higher than patients treated with induction CT + cCRT with intensity-modulated radiotherapy (IMRT), respectively. The IT had no impact on OS in neither patients with EBER+ nor in patients with EBER-; IT showed better DFS in EBER+ but not in patients with EBER-. Conclusions: In low-incidence areas, patients with NPC treated with induction CT followed by concurrent IMRT cCRT achieved the highest DFS rate. The benefit of IT on DFS was restricted to patients with EBERthorn, suggesting that additional therapy offers no advantages in EBER- cases. (C) 2021 Elsevier Ltd. All rights reserved.

Supplemental material, Supplementary_Material_-_online_only for Symptomatic COVID-19 in advanced-cancer patients treated with immune-checkpoint inhibitors: prospective analysis from a multicentre observational trial by FICOG by Melissa Bersanelli, Diana Giannarelli, Ugo De Giorgi, Sandro Pignata, Massimo Di Maio, Elena Verzoni, Alberto Clemente, Valentina Guadalupi, Diego Signorelli, Marcello Tiseo, Raffaele Giusti, Marco Filetti, Marilena Di Napoli, Lorenzo Calvetti, Alessandro Cappetta, Paola Ermacora, Diego Zara, Fausto Barbieri, Cinzia Baldessari, Vieri Scotti, Francesca Mazzoni, Antonello Veccia, Pamela Francesca Guglielmini, Marco Maruzzo, Ernesto Rossi, Francesco Grossi, Chiara Casadei, Alessio Cortellini, Francesco Verderame, Vincenzo Montesarchio, Mimma Rizzo, Manlio Mencoboni, Fable Zustovich, Lucia Fratino, Saverio Cinieri, Giorgia Negrini, Maria Banzi, Mariella Sorarù, Paolo Andrea Zucali, Gaetano Lacidogna, Antonio Russo, Nicola Battelli, Giuseppe Fornarini, Claudia Mucciarini, Sergio Bracarda, Andrea Bonetti, Debora Pezzuolo, Lucia Longo, Donata Sartori, Mauro Iannopollo, Luigi Cavanna, Fausto Meriggi, Davide Tassinari, Claudia Corbo, Angela Gernone, Veronica Prati, Simona Carnio, Pasqualina Giordano, Angela Maria Dicorato, Claudio Verusio, Francesco Atzori, Francesco Carrozza, Stefania Gori, Antonino Castro, Sara Pilotto, Vanja Vaccaro, Elisabetta Garzoli, Francesco Di Costanzo, Evaristo Maiello, Roberto Labianca, Carmine Pinto, Michele Tognetto and Sebastiano Buti in Therapeutic Advances in Medical Oncology

Background:This prospective, multicentre, observational INVIDIa-2 study is investigating the clinical efficacy of influenza vaccination in advanced-cancer patients receiving immune-checkpoint inhibitors (ICIs), enrolled in 82 Italian centres, from October 2019 to January 2020. The primary endpoint was the incidence of influenza-like illness (ILI) until 30 April 2020. All the ILI episodes, laboratory tests, complications, hospitalizations and pneumonitis were recorded. Therefore, the study prospectively recorded all the COVID-19 ILI events.Patients and methods:Patients were included in this non-prespecified COVID-19 analysis, if alive on 31 January 2020, when the Italian government declared the national emergency. The prevalence of confirmed COVID-19 cases was detected as ILI episode with laboratory confirmation of SARS-CoV-2. Cases with clinical-radiological diagnosis of COVID-19 (COVID-like ILIs), were also reported.Results:Out of 1257 enrolled patients, 955 matched the inclusion criteria for this unplanned analysis. From 31 January to 30 April 2020, 66 patients had ILI: 9 of 955 cases were confirmed COVID-19 ILIs, with prevalence of 0.9% [95% confidence interval (CI): 0.3–2.4], a hospitalization rate of 100% and a mortality rate of 77.8%. Including 5 COVID-like ILIs, the overall COVID-19 prevalence was 1.5% (95% CI: 0.5–3.1), with 100% hospitalization and 64% mortality. The presence of elderly, males and comorbidities was significantly higher among patients vaccinated against influenza versus unvaccinated ( p = 0.009, p Conclusion:COVID-19 has a meaningful clinical impact on the cancer-patient population receiving ICIs, with high prevalence, hospitalization and an alarming mortality rate among symptomatic cases. Influenza vaccination does not protect from SARS-CoV-2 infection.

Angiogenesis has been recognized as the most important factor for tumor invasion, proliferation, and progression in metastatic renal cell carcinoma (mRCC). However, few clinical data are available regarding the efficacy of cabozantinib following immunotherapy.To describe the outcome of cabozantinib in patients previously treated with immunotherapy.Patients with mRCC who received cabozantinib immediately after nivolumab were included. The primary endpoint was to assess the outcome in terms of efficacy and activity.Eighty-four mRCC patients met the criteria to be included in the final analysis. After a median follow-up of 9.4 months, median overall survival was 17.3 months. According to the IMDC criteria, the rates of patients alive at 12 months in the good, intermediate, and poor prognostic groups were 100%, 74%, and 33%, respectively (p 0.001). The median progression-free survival (PFS) was 11.5 months (95% CI 8.3-14.7); no difference was found based on duration of previous first-line therapy or nivolumab PFS. The overall response rate was 52%, stable disease was found as the best response in 25.3% and progressive disease in 22.7% of patients. Among the 35 patients with progressive disease on nivolumab, 26 (74.3%) patients showed complete/partial response or stable disease with cabozantinib as best response after nivolumab. The major limitations of this study are the retrospective nature and the short follow-up.Cabozantinib was shown to be effective and active in patients previously receiving immune checkpoint inhibitors. Therefore, cabozantinib can be considered a valid therapeutic option for previously treated mRCC patients, irrespective of the type and duration of prior therapies.

Pazopanib is a standard first-line treatment for metastatic clear-cell renal cell carcinoma (ccRCC). Very few data on its activity in non-clear-cell renal cell carcinoma (nccRCC) are currently available. The aim of this study was to retrospectively analyze efficacy and toxicity of pazopanib in nccRCC patients.Records from advanced nccRCC patients (consecutive sample) treated with first-line pazopanib between 2010 and 2015 at 17 Italian centers were reviewed. Response rate, progression-free survival (PFS), and overall survival (OS) were evaluated. Univariate and descriptive analyses were performed.Thirty-seven patients with nccRCC were treated with first-line pazopanib; 51% had papillary histology, 24% chromophobe, 22% unclassified, and 3% had Xp11.2 translocation. Dose reductions/temporary interruptions for toxicity were required in 46% of cases. Grade (G) 3/4 toxicity was seen in 32%, G1/2 in 89% of cases; 81% achieved disease control, with 10 partial responses (27%) and 20 cases of stable disease (54%); 16% of patients had disease progression as best response. Median PFS and OS were 15.9 and 17.3 months, respectively. In univariate analysis, nephrectomy (P = .020), Memorial Sloan Kettering Cancer Center (MSKCC) score (P .001), basal neutrophil/lymphocyte ratio (NLR; P = .009) and performance status (PS) (P = .001) were associated with PFS; MSKCC score (P .001), International Metastatic Renal Cell Carcinoma Database Consortium score (P = .003), PS (P .0001), nephrectomy (P = .002), histology (P = .035), dose reductions/interruptions (P = .039), best response to treatment (P .001), and NLR (P = .008) were associated with OS.In nccRCC patients, treatment with pazopanib was effective and feasible; dose reductions required for toxicity were similar as expected in ccRCC.

Introduction Gefitinib, erlotinib, and afatinib represent the approved first-line options for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Because pivotal trials frequently lack external validity, real-world data may help to depict the diagnostic-therapeutic pathway and treatment outcome in clinical practice. Methods MOST is a multicenter observational study promoted by the Veneto Oncology Network, aiming at monitoring the diagnostic-therapeutic pathway of patients with nonsquamous EGFR-mutant NSCLC. We reported treatment outcome in terms of median time to treatment failure (mTTF) and assessed the impact of each agent on the expense of the regional health system, comparing it with a prediction based on the pivotal trials. Results An EGFR mutation test was performed in 447 enrolled patients, of whom 124 had EGFR mutation and who received gefitinib (n = 69, 55%), erlotinib (n = 33, 27%), or afatinib (n = 22, 18%) as first-line treatment. Because erlotinib was administered within a clinical trial to 15 patients, final analysis was limited to 109 patients. mTTF was 15.3 months, regardless of the type of tyrosine kinase inhibitor (TKI) used. In the MOST study, the budget impact analysis showed a total expense of €3,238,602.17, whereas the cost estimation according to median progression-free survival from pivotal phase III trials was €1,813,557.88. Conclusion Good regional adherence and compliance to the diagnostic-therapeutic pathway defined for patients with nonsquamous NSCLC was shown. mTTF did not significantly differ among the three targeted TKIs. Our budget impact analysis suggests the potential application of real-world data in the process of drug price negotiation. Implications for practice The MOST study is a real-world data collection reporting a multicenter adherence and compliance to diagnostic-therapeutic pathways defined for patients with epidermal growth factor receptor-mutant non-small cell lung cancer. This represents an essential element of evidence-based medicine, providing information on patients and situations that may be challenging to assess using only data from randomized controlled trials, e.g., turn-around time of diagnostic tests, treatment compliance and persistence, guideline adherence, challenging-to-treat populations, drug safety, comparative effectiveness, and cost effectiveness. This study may be of interest to various stakeholders (patients, clinicians, and payers), providing a meaningful picture of the value of a given therapy in routine clinical practice.

Despite the well-known negative prognostic value of theTwo large retrospective series ofA total of 395These scoring systems are based on easy-to-collect data and defined specific subgroups with relevant differences in their life expectancy. These tools could be useful in clinical practice, would allow better stratification of patients in clinical trials and may be adopted for proper adjustments in exploratory translational analyses.

Background The ROXANE Italian prospective study evaluated the impact of the 21-gene Recurrence Score (RS) results on adjuvant treatment decision for patients with early breast cancer. Materials and Methods Nine centers participated. Physicians used the RS test whenever unsure about adjuvant treatment recommendation for patients with estrogen receptor-positive/human epidermal growth receptor 2-negative, T1–T3, N0–N1 early breast cancer. Pre-RS and post-RS treatment recommendations were collected. Results A total of 251 patients were included. N0 patients (61%) showed higher grade (p < .001) and higher Ki67 (p = .001) and were more frequently progesterone receptor negative (p = .012) as compared with N1 patients. RS results were as follows: Conclusion Physicians predominantly used the 21-gene assay in N0 patients with a more aggressive biology or in N1 patients showing more indolent biology. In this selected patient population, the use of RS testing led to a 30% rate of change in treatment decision. In the N1 patient subgroup, the use of RS testing contributed to reduce CT use by more than half. Implications for Practice This study shows that, even in a context in which physicians recommend a high proportion of patients to endocrine treatment alone before knowing the results of the Recurrence Score (RS) assay, the use of the RS test, whenever uncertainty regarding adjuvant treatment recommendation is present, significantly contributes in further reducing the use of chemotherapy, especially for N1 patients.

Background Despite the well-known negative prognostic value of the V600EBRAF mutation in patients with metastatic colorectal cancer (mCRC), its outcome is quite heterogeneous, and the basis for this prognostic heterogeneity should be better defined. Methods Two large retrospective series of V600EBRAF-mutated mCRC from 22 institutions served as an exploratory and validation set to develop a prognostic score. The model was internally and externally validated. Results A total of 395 V600EBRAF-mutated mCRCs were included in the exploratory set. Performance status, CA19.9, lactate dehydrogenase, neutrophil/lymphocyte ratio, grading and liver, lung and nodal involvement emerged as independent prognostic factors for overall survival (OS). Two different scoring systems were built: a ‘complete’ score (0–16) including all significant covariates and a ‘simplified’ score (0–9), based only on clinicopathological covariates, and excluding laboratory values. Adopting the complete score, proportions of patients with a low (0–4), intermediate (5–8) and high (9–16) score were 44.7%, 42.6% and 12.6%, respectively. The median OS was 29.6, 15.5 (hazard ratio [HR] for intermediate vs low risk: 2.16, 95% confidence interval [CI]: 1.44–3.22, p Conclusions These scoring systems are based on easy-to-collect data and defined specific subgroups with relevant differences in their life expectancy. These tools could be useful in clinical practice, would allow better stratification of patients in clinical trials and may be adopted for proper adjustments in exploratory translational analyses.

290 Background: Second (2L) or third-line (3L) treatment options for mRCC have dramatically changed in the last years. The standard of care as per Italian Regulatory Agencies approvals is N or C. To date, there are no criteria for the choice between N and C, which both demonstrated OS gain in the pivotal trials. Methods: We planned a retrospective, real world analysis of the use of N and C as 2L and 3L treatment in 17 Oncology Units of Veneto Region. All consecutive patients (pts) with mRCC treated in advanced setting in 2017-2018 were included. Results: We identified 170 pts, 73% males, median age 68.4 years. All pts started a 2L treatment while only 59% received a 3L treatment. In our cohort, patients with NLR > 3 at treatment start had a shorter OS (43 vs 90 months (mos), p < 0.0001); IMDC classification maintained its prognostic role. In 2L, N was administrated in 108 pts (63%), C in 29 pts (17%); in 3L N was administrated in 42 pts (25%), C in 49 pts (29%). Reported oncologists’ reasons for 2L choice were: change of mechanism of action compared to first line (28%), response to previous TKI (21.2%), intolerance to TKI (17.6%), previous toxicity (12.9%), tumor burden (11.2%), age of the patient (4.1%). Median OS and PFS in 2L were 28.4 and 6.6 mos for N, 16.8 and 6.6 mos for 2L C. Median OS and PFS in 3L were 27 and 5.2 mos for N, 16.6 and 7.5 mos for C. 46 pts received the sequence of drugs N > C, 12 the opposite sequence C > N. Median OS for N > C vs C > N were 96.6 vs 36 mos (p > 0.0001); median PFS for both the sequences were similar at 5.7 mos (p = ns). The cost per patient of the sequence N > C is 51.606 € while for the sequence C > N is 31.480,00 €. Between the two sequences a cost effectiveness per month of survival analysis was performed: the cost per month of OS for the sequence N > C was 534,18 € while for the sequence C > N was 874,46 €, heavily higher. Conclusions: In our real-world setting cohort, most of the pts received N as 2L treatment and a minority received C. Outcome of single drug are superimposable to published literature. With the limits of the retrospective nature of the study, with a cost per month of OS lower a much longer OS, the sequence N > C appear to be a better treatment strategy.

While typesetting the article the Table 3 column/row entries are interchanged. Please find below the updated Table.

4002 Background: Data on first-line treatment efficacy in elderly patients are limited. Many analyses adopt a questionable cut-off of 65 years and specific evidence with anti-EGFRs is low. FOLFOX-panitumumab (pan) is an option for RAS wild-type (wt) untreated mCRC patients. Guidelines recommend considering fluoropyrimidine monotherapy as an option for elderly patients, but no randomized studies have ever explored the role of the combination with an anti-EGFR. Methods: This is a prospective, open-label, multicenter phase II randomized trial. Unresectable and previously untreated RAS- BRAF wt mCRC patients aged ≥70 were randomized to receive FOLFOX-pan (arm A), or 5FU/LV-pan (arm B) for up to 12 cycles followed by pan maintenance until PD. The primary EP was PFS in both arms. Stratification criteria were age (≤75 vs > 75 years), ECOG PS (0–1 vs 2) and geriatric assessment with G8 Score (≤14 vs > 14). In each treatment arm, the null hypothesis for median PFS was set at ≤6 months. Assuming an expected median PFS time ≥9.5 months with both experimental regimens, a sample size of 90 patients in each arm granted to the study a power of 90%, with a type I error rate equal to 5% (1-sided Brookmeyer-Crowley test) for rejecting the null hypothesis. No formal comparison between the two arms was planned. Results: From Jul 2016 to Apr 2019 a total of 394 patients were screened, 211 were deemed eligible for inclusion and 185 were randomized (92 arm A and 93 arm B). Main pts’ characteristics were (arm A/B): males 66%/61%; median age 77/77y; PS≥1 49%/55%; right colon 23%/21%; G8 > 14 31%/30%. At a median follow up of 20.5 mos, 135 (arm A/B: 64/71) PD events were collected. Median PFS was 9.6 (95% CI 8.8-10.9) in arm A with FOLFOX-pan and 9.1 (95% CI 7.7-9.9) in arm B with 5FU/LV-pan. Response rates were (arm A/B): 65%/57%. Grade 3-4 toxicities were (arm A/B): neutropenia 9.8%/1.1%; diarrhea 16.3%/1.1%; stomatitis 9.8%/4.4%; neurotoxicity 3.3%/0%; fatigue 6.5%/4.4%; skin rash 25%/24.2%, hypomagnesemia 3.3%/7.7%. Conclusions: Large prospective randomized studies in molecularly selected elderly mCRC are feasible with multicenter collaborative efforts. Primary EP was met in both treatment arms. 5FU/LV plus panitumumab for up to 12 cycles followed by panitumumab maintenance until PD might be a reasonable option in elderly mCRC patients with RAS/BRAF wt tumors deserving further investigations in phase III trials. Clinical trial information: NCT02904031 .

1. Abstract 1.1. Background: Complementary and Alternative medicine (CAM) is commonly used by cancer patients (pts). Recent randomised controlled trials showed that acupuncture is safe, effective and feasible for the management of cancer-related fatigue and other adverse events of anti-neoplastic therapies. 1.2. Materials and Methods: Since November 2012 we have been offering a supportive care program of 20 minutes’ weekly session of acupuncture for the management of chemotherapy-induced nausea/vomiting, hot flashes, cancer-related fatigue, xerostomia. A brochure regarding indications and techniques was offered to all cancer patients who received a systemic anticlastic therapy (Chemotherapy, Target Therapy, Endocrine Treatment) and/or radiation therapy. 1.3. Results: More than 500 pts affected by solid tumours or lymphoma were treated in our Operative Unit during the period of the project. None of them preferred to receive acupuncture in addition to the specific pharmacological treatment. 1.4. Conclusion: Cancer pts of the district of Belluno, Italy did not demonstrate any interest in acupuncture for the management of side effects of anti-neoplastic treatments.

The skeleton is the target tissue for many types of tumors, and, recently, the survival of patients with prostate cancer metastasis has been increased using α-emitting drugs known as targeted α therapies. The use of α-radiopharmaceuticals in medicine was hypothesized at the beginning of the nineteenth century after the observation that α-radionuclides were associated with high cell-killing energy and low tissue penetration in healthy tissues. In the prostate cancer (PC) scenario, current research suggests that this class of radiopharmaceuticals has limited toxicity, and that the mechanism of action does not overlap with pre-existing drugs, allowing us to extend therapeutic armaments and address medical oncology towards personalized and precision medicine. Ongoing studies may extend these benefits also to bone metastases deriving from other neoplasms. The aim of this review is to summarize the current research on targeted α therapies and try to identify the right patient to be treated in the right time in order to integrate in these medications in the every-day clinical practice.

To assess the safety and efficacy of abiraterone acetate (AA) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated in a compassionate named patient programme (NPP). We retrospectively reviewed the clinical records of patients with mCRPC treated with AA at the standard daily oral dose of 1000 mg plus prednisone 10 mg/day in 19 Italian hospitals. We assessed 265 patients with mCRPC treated with AA. The most frequent (>1%) grade 3–4 toxicities were anaemia (4.2%), fatigue (4.2%), and bone pain (1.5%). The median progression-free survival was 7 months; median overall survival was 17 months after starting AA, and 35 months after the first docetaxel administration. Our study reproduced the clinical outcomes reported in the AA pivotal trial, including those relating to special populations such as the elderly, patients with a poor performance status, symptomatic patients, and patients with visceral metastases. Our data show the safety and activity of AA when administered outside clinical trials, and confirm the findings of the post-docetaxel pivotal trial in the patients as a whole population and in special populations of specific interest.

Background: Bevacizumab is a recombinant humanized monoclonal antibody that obstructs the vascular endothelial growth factor (VEGF) pathway. Despite its extensive employment in the treatment of primary tumors of the brain, experience of brain metastatic disease, a frequent complication in patients with lung cancer, is very limited. On the basis of the strong antiedemigenous effect and no risk of intracranial bleeding, we administered a bevacizumab-based chemotherapy to patients with non-small-cell lung cancer (NSCLC) and symptomatic metastatic brain lesions who were not suitable candidates for a specific local therapy. Methods: The patients received bevacizumab 7.5 mg/kg and cisplatin 75 mg/m2 on day 1, and gemcitabine 1,250 mg/m2 on days 1 and 8, every 21 days. Results: We studied 13 patients with clinical and radiological progressive brain metastases; the majority had a treatment-naïve disease. Bevacizumab-based chemotherapy was found to be well tolerated and effective: progression-free survival (PFS) was 9.1 months (range: 0.9-39.2+) and overall survival (OS) was 9.6 months (range 3-41.5+). Conclusions: Bevacizumab-based therapy proved to be feasible and safe. The PFS and the OS data are very encouraging as well as the symptomatic benefit due to bevacizumab's high capacity to provide a long-lasting decrease of perilesional edema.

Treatment with angiogenesis inhibitors is becoming a cornerstone of modern anticancer therapy. Hypertension (HTN) is a common adverse event during antiangiogenic treatment and might represent a cancer biomarker in patients with recurrent glioblastoma treated with angiogenesis inhibitors. In a retrospective study, we analyzed 53 patients with recurrent glioblastoma treated with antiangiogenic drugs. Thirty patients were treated with sorafenib and 23 patients were treated with bevacizumab. All patients underwent brain gadolinium-enhanced MRI assessments according to the Radiologic Assessment in Neuro-Oncology criteria every 2 months or when clinically indicated. Blood pressure was measured before and during the treatment. We investigated whether treatment-related HTN may be associated with outcome in patients treated with antiangiogenic drugs. After 2 months of treatment, 24 patients (45%) achieved disease control: stable disease (17 patients) or a partial response (seven patients). The median overall survival from the start of antiangiogenic treatment was 7.3 months [95% confidence interval (CI) 6.02-8.5]; the median progression-free survival (PFS) was 2.7 months (95% CI 1.5-3.5); and the 6-month PFS was 32%. Twenty patients (38%) developed grades 2-3 HTN within 2 months of treatment. A significant association was found between HTN and disease control rate, and HTN and 6-month PFS; no significant association was found between HTN and the median PFS. According to univariate and multivariate analyses, HTN was related to a longer survival from antiangiogenic drug administration: 9.8 versus 4.8 months (P=0.001; hazard ratio=3.5, 95% CI 1.6-7.6). Our data indicate that HTN may be an effective biomarker in patients with recurrent glioblastoma treated with antiangiogenic drugs; in particular, it may be associated with a favorable effect on disease control, 6-month PFS, and the median overall survival.

Bone metastases affect the majority of patients with castration-resistant prostate cancer (CRPC), resulting in significant morbidity and mortality. This review describes the current therapies available for the management of CRPC patients with bone metastases. Areas covered: Studies on the use of currently available therapeutic approaches for palliating pain, delaying skeletal-related events (SREs) and prolonging survival in CRPC patients with bone metastases have been examined. PubMed database was searched in May 2016 starting with the following keywords: ('castration-resistant prostate cancer' OR 'CRPC') AND 'bone metastases', and approximately 270 results were retrieved. More specific searches were then performed on the epidemiology and molecular pathogenesis (in particular, 'vicious cycle' was used as a keyword), the management of pain, SREs and survival. The following keywords were also used individually: abiraterone, cabazitaxel, denosumab, docetaxel, enzalutamide, radium-223, sipuleucel-T, samarium-153, strontium-89, zoledronate. Randomized-controlled trials, observational studies, reviews, systematic reviews and meta-analyses were selected and articles were excluded if not in English. Expert commentary: Currently, clear recommendations on the optimal use of the agents available to treat mCRPC are lacking. Therefore, to ensure patients the best treatment, both their clinical characteristics and the features of each product have to be considered.

Aim, patients & methods: To evaluate the real-world setting use of sunitinib, we reviewed data of our patients from January 2007 to December 2014. Results: In 114 patients, sunitinib was used as first-line TKI. Out of 110 evaluable patients, 5 complete responses, 37 partial responses, 42 stabilizations were reported. Median progression-free survival and overall survival (OS) were 14.3 and 28.4 months. Patients who received ≥4 full-dose cycles had a better OS (p = 0.02). A neutrophil–lymphocyte ratio

Background: In cancer patients, including women with a diagnosis of ovarian cancer, cancer antigen 125 (CA125) is used to evaluate the presence of peritoneal involvement. The aims of the present study were to assess CA125 reference intervals and reference change values (RCV) in postmenopausal reference women, postmenopausal women breast cancer free, reference men and cancer free men. Methods: The series consisted of 433 subjects: 105 postmenopausal breast cancer free women and 56 cancer free men in addition to a total of 272 reference subjects (145 postmenopausal women and 127 men). Repeated CA125 measurements were made in a subset of 149 women and 54 men to calculate RCV and index of individuality. Serum CA125 levels were evaluated by a chemiluminescent assay. Results: In postmenopausal reference women, the mean CA125 value and 2.5th–97.5th percentiles were 6.70, 2.60–11.00 kU/L, respectively, with a unidirectional RCV of 38.4%. In postmenopausal breast cancer free women, the mean CA125 value and 2.5th–97.5th percentile were 7.45, 4.09–10.92 kU/L, respectively, with a RCV of 34.5%. The difference between the means was statistically significant (t=–3.02, p=0.003). In the two male subgroups, the difference between the means for CA125 was not statistically significant (t=0.43, p=0.665). On considering the entire male population, the mean CA125 value and 2.5th–97.5th percentiles were 7.50 and 2.40–13.2 kU/L, respectively, while the unidirectional RCV was 34.3%. In all the studied groups, the indices of individuality were equal to or below 0.6. Conclusions: The extremely low index of individuality found underlines the importance of using the RCV instead of absolute values as a parameter when interpreting the CA125 data in the monitoring and follow-up of patients with ovarian cancer.

The wide availability of drugs for the treatment of advanced renal cell carcinoma has recently provided many alternatives for patients historically treated with immunotherapy alone. The six drugs currently available for the treatment of metastatic renal cell carcinoma became available to physicians after the approval processes performed by regulatory agencies, based mainly on the results of Phase III studies. Owing to the stringent entry criteria of the studies, patients are not representative of the entire population. Results of Phase III studies are extrapolated to all renal cell carcinoma populations without taking into account patients with different comorbidities. The purpose of this review is to analyze and weigh the safety data available for the drugs approved for metastatic renal cell carcinoma and to suggest the best therapy in terms of both efficacy and safety based on the multiplicity of features of each patient in relation to the main characteristics of each agent.

In the last 5 years inhibitors of the VEGF/VEGFR and mTOR pathways have dramatically changed the therapeutic approach to metastatic renal cancer. Randomized controlled trials have shown that six targeted agents – sorafenib, sunitinib, temsirolimus, bevacizumab, everolimus and pazopanib – are able to improve patient outcome. Even if the choice of drug for first-line therapy is quite well defined, to date it is not easy to characterize and evaluate the efficacy of new therapies in second-line treatment. It is not clear whether, after first-line therapy with a VEGF/VEGFR inhibitor, use of mTOR or a second TKI inhibitor should be recommended. In this review we report on current evidence supporting the use of targeted agents in second-line therapy. Therefore we try to combine current clinical results with a practical clinical approach, with the goal of evaluating the best clinical decision for different clinical situations.

Mitomycin C (MC) is used as therapy against solid tumors, also combined with other chemotherapeutic agents or radiotherapy. It may cause acute, subacute, or chronic anemia capable of modifying the results of chemo- and radiotherapy. Erythropoietin may be lowered by cancer itself or because of chemoradiotherapy. There are few studies investigating the relationship between erythropoietin and chronic anemia.We prospectively analyzed the chronic anemia and erythropoietin in 38 patients with solid cancer. Patients were 40 to 82 years of age. MC was randomly given every 3 weeks as a single drug at 10 or 20 mg/m². When myelotoxicity occurred the next therapy cycle was delayed until recovery. RBC indices, hemolysis, erythropoietin, liver and kidney function were studied. MC cycles were 136 (3.6 ± 1.4 per pt), 32 being delayed because of myelotoxicity.Hematocrit, hemoglobin and RBC were inversely related to the cumulative dose (r = 0.70 to 0.86; p 0.03 to 0.01) of MC. Other tests remained stable. Anemia occurred almost twofold earlier in the 20 mg/m² group (p=0.049). basal erythropoietin, already lower than in age and sex watched 81 non cancerous subjects (p0.001), decreased during MC therapy (p0.01). For each given MC mg/m² a 0.0372 Hb mg/dl reduction occurred. Chronic anemia due to MC is accompanied by erythropoietin reduction. These results can help in designing chemoradiotherapy.

Learning Objectives After completing this course, the reader will be able to: Compare the use of i.t. therapy and systemic therapies for patients with neoplastic meningitis.Describe new drugs showing promise for neoplastic meningitis. This article is available for continuing medical education credit at CME.TheOncologist.com Neoplastic meningitis is a result of the spread of malignant cells to the leptomeninges and subarachnoid space and their dissemination within the cerebrospinal fluid. This event occurs in 4%–15% of all patients with solid tumors and represents an important prognostic factor for poor survival. Neoplastic meningitis should be diagnosed in the early stages of disease to prevent important neurological deficits and to provide the most appropriate treatment. Despite new diagnostic approaches developed in recent years, such as positron emission tomography–computed tomography and new biological markers, the combination of magnetic resonance imaging without and with gadolinium enhancement and cytology still has the greatest diagnostic sensitivity. Recently, no new randomized studies comparing intrathecal (i.t.) with systemic treatment have been performed, yet there have been a few small phase II studies and case reports about new molecularly targeted substances whose successful i.t. or systemic application has been reported. Trastuzumab, gefitinib, and sorafenib are examples of possible future treatments for neoplastic meningitis, in order to better individualize therapy thus allowing better outcomes. In this review, we analyze the most recent and interesting developments on diagnostic and therapeutic approaches.

Study Type – Therapy (RCT) Level of Evidence 1b What’s known on the subject? and What does the study add? Data on quality of life during docetaxel treatment in castration resistant prostate cancer was mainly provided by SWOG and TAX327 trials. In the TAX327 trial biochemical response and pain predicted survival, whereas quality of life outcomes did not. In the present study, there were no statistically significant changes in the quality of life scales during treatment except in the case of patients receiving docetaxel and estramustine, who experienced a significant decrease in pain. Our data seem to suggest that patients with a better baseline quality of life (and consequently with fewer symptoms) are more likely to achieve a biochemical response. OBJECTIVES • To assess quality of life (QoL) outcomes and pain changes in patients affected by castration-resistant prostate cancer enrolled in a phase II randomized trial of 3-week docetaxel (DOC)-based chemotherapy. • To provide further data to clarify the conflicting published data concerning the impact of DOC on the patients’ QoL. PATIENTS AND METHODS • QoL outcomes were assessed using the European Organisation for the Research and Treatment of Cancer QLQ-C30 questionnaire. • Pain changes were evaluated by means of the Brief Pain Inventory at baseline and after every two DOC courses. • The patients completing at least two questionnaires (at baseline and before the third course) were considered evaluable. RESULTS • In all, 59 patients were evaluable. • Asymptomatic patients and responders had a better baseline QoL than symptomatic patients and non-responders. • There were no statistically significant changes in the QLQ-C30 scales during treatment except in the case of patients receiving DOC and estramustine, who experienced a significant decrease in pain. • There was a progressive improvement in the mean intensity and interference scores of the Brief Pain Inventory. CONCLUSIONS • Our data confirm that QoL is generally maintained during chemotherapy. • There is a substantial reduction in pain. • Our results also suggest that baseline QoL may predict treatment response.

Study Type – Therapy (retrospective cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Various targeted agents with differing mechanisms of action and toxicity profiles have now been approved for the treatment of advanced RCC. However, the optimal use of these agents remains a challenge. Since the approval of sorafenib and sunitinib, many patients have been treated with these two tyrosine kinase inhibitors (TKIs) in sequence, with current evidence suggesting that this approach is associated with continued clinical benefit, with limited or no cross-resistance between the two agents. The mammalian target of rapamycin (mTOR) inhibitor, everolimus, has been shown to be as effective after two TKIs as it is after one TKI, emphasizing the importance of understanding the optimal TKI sequence before switching to an mTOR inhibitor, to provide patients with the longest progression-free survival (PFS) benefit. This retrospective analysis of 189 patients treated sequentially with sorafenib (800 mg/day) and sunitinib (50 mg/day; 4 weeks on 2 weeks off) showed that initial therapy with either agent was associated with similar PFS benefits (median PFS 8.4 months [sorafenib] vs 7.8 months [sunitinib]; HR 1.05, 95% CI 0.78–1.40; P = 0.758). However, patients treated with sorafenib followed by sunitinib (SoSu) appeared to derive a greater PFS benefit than those treated with SuSo (median PFS with second TKI: 7.9 months [SoSu] vs 4.2 months [SuSo]; HR 0.54, 95% CI 0.39–0.74; P

Chemotherapy induced cardio-toxicity is a well known side effect of anticancer treatments, moreover the 70% of all tumors involve patients over 65 years-old, frequently with cardiac co- morbidity. We evaluated the feasibility of the application during chemotherapy administration of some of the most recent diagnostic techniques as 12-diagnostic leads telemetry, 7 days EKG monitoring device (R-Test Evolution 3R), blood level dosage of Brain Natriuretic Peptide (BNP) and Ischemia Modified Albumin (IMA). Some sub-clinical changes in the investigated parameters were found in patients undergoing chemotherapy, mostly containing fluorouracil, as shown in the following paper. Far from suggesting a widespread use of these methods during chemotherapy administration, we think that some more tools are needed to prevent cardiac toxicity in high-risk patients and some of what we studied may deserve further valuation in chemotherapy clinical trials.

Prevalence of symptomatic central nervous system (CNS) metastases among patients with breast cancer ranges from 5% to 16%, although autoptic studies have reported prevalence rates of up to 30%. Solid brain tumours are the most common presentation in the CNS (85-95%), and they tend to arise at the grey-white matter junction with a distribution that is proportional to the regional cerebral blood flow. Descriptions of solitary intra-ventricular metastasis are very rare; to date no cases from breast cancer have been reported in the literature. We present the unusual case of a breast cancer patient who developed a solitary choroid plexus metastasis in the left lateral ventricle.

PURPOSE A morphofunctional approach to the management of brain tumours has been claimed to increase diagnostic accuracy. Among the proposed single-photon emission tomography (SPET) tracers, (99m)Tc-sestamibi is able to distinguish recurrent tumour from radio-necrosis and to identify early response or resistance to chemotherapy. Major drawbacks of sestamibi, that is, poor morphological resolution and the sites of physiological uptake, could be overcome by dual-modality, integrated systems. The purpose of this study was to investigate the real usefulness of (99m)Tc-sestamibi SPET/computed tomography (CT) and to establish a semiquantitative index. METHODS Charts from 33 consecutive patients selected for surgery, who underwent preoperative SPET/CT and magnetic resonance imaging (MRI), were reviewed. Tumours were confirmed histologically after the surgery in all patients and classified according to WHO recommendations. Semiquantitative indexes were obtained on images (maximum likelihood expectation maximization reconstructed) with and without attenuation correction and visual analysis of SPET versus SPET/CT was performed. RESULTS A significant statistical difference was shown between SPET and SPET/CT in terms of the delineation of medial shift, oedema and the ability to distinguish tumour from the skull-meninges complex and plexus. With regard to semiquantitative indexes, a ratio obtained comparing counts/pixel derived from a region of interest in the tumour area with mirrored region of interest in the contralateral site revealed a sensitivity of 90.9% and specificity of 71.45% in discriminating WHO grade 4 gliomas from a lower grade. CONCLUSION SPET/CT can distinguish tumour from the skull and other sites of physiological uptake better than SPET alone (as confirmed by MRI in all cases) and affords a morphological map. The proposed semiquantitative index also seems promising in identifying higher-grade disease. SPET/CT thus seems a useful additional tool in brain tumour management, especially when MRI is not feasible or PET/CT is not available.

To investigate the allelic status of the thymidylate synthetase (TYMS) gene, located at chromosome band 18p11.32, in renal cell carcinoma (RCC). TYMS is a key target of the 5-fluorouracil (5-FU)-based class of drugs, frequently considered in combination therapies in advanced RCC. TYMS variants, such as the TYMS polymorphic 5′-untranslated region variable number tandem repeat sequence (VNTR), are under investigation to guide 5-FU treatment. Yet, no information is available with regard to changes in TYMS allele frequencies in RCC malignances. Blood and matched tumor samples were collected from 41 histological proven clear cell RCC affected patients (30 males, 11 females.). TYMS VNTR genotype was first determined in blood to identify heterozygotes employing PCR techniques. To evaluate for allelic imbalance, fragment analysis was performed both in blood and matched tumor DNA of the heterozygote patients. Microsatellite analysis, employing the markers D18S59 and D18S476 mapping, respectively, at the TYMS locus (18p11.32) and 1.5 Mb downstream of the TYMS gene sequence (18p11.31), was performed to confirm TYMS allelic imbalance in tumors. Germ-line TYMS VNTR distribution was: 2R/2R (19.5%), TYMS 2R/3R (36.6%) and TYMS 3R/3R (43.9%). Allelic imbalance for the TYMS tandem repeat region was detected in 26.6% of the heterozygote patients. Microsatellite analysis confirmed the allelic imbalance detected by TYMS VNTR analysis and revealed that the overall frequence of allelic imbalance of chromosome band 18p11.32 was 35%, while the overall allelic imbalance of chromosome band 18p11.31 was 28%. By focusing on the TYMS polymorphic variants in renal cancer, we here provide evidence, to our knowledge, for the first time showing loss of 18p11.32 and 18p11.31 in renal cell carcinomas. As allelic imbalances involving TYMS locus may be an important variable affecting 5-FU responsiveness, this study may contribute to explain different responses of advanced RCC in combined chemotherapeutic regimens incorporating fluoropyridines.

OBJECTIVE To report the results of a randomized phase II trial of docetaxel with and without estramustine phosphate (EP) in patients with hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS Patients with progressive HRPC were randomized to receive docetaxel 70 mg/m2 on day 1 (arm A), or docetaxel 70 mg/m2 on day 2 plus oral EP three times daily, at a total daily dose of 840 mg, on days 1–5 (arm B). The primary objective of the trial was to evaluate the activity of the treatments in terms of the response in prostate-specific antigen (PSA) level. RESULTS Forty-five of the 49 patients centrally randomized to arm A and 44 of the 46 in arm B were evaluable for activity. The PSA level decreased by ≥50% in 40% of the patients in arm A and in 75% of those in arm B. The median time to PSA progression was 20 weeks in arm A and 30 weeks in arm B. The patients in arm B had an improvement in pain over time. CONCLUSION These data support the existence of a possible advantage in combining docetaxel and EP, which should be verified in a specific randomized phase III study.