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5041 Background: Ra-223 extends OS in pts with mCRPC. Predictive markers of response to Ra-223 are needed to help select pts who would benefit most from Ra-223 therapy. The ALSYMPCA study suggested a correlation between ALP decline and longer OS. Here, we evaluated whether ALP decline is associated with OS in the global real-world REASSURE study. Methods: Pts treated with Ra-223 were grouped by baseline ALP ≤147 U/L vs >147 U/L and any ALP decline vs no decline at week 12 from the first Ra-223 dose. The 147 U/L cut-off was selected based on the highest upper limit of normal for ALP from literature. Pts with a trend of decreasing ALP at closest value to week 12 between weeks 8 and 16 were included in the any decline group. Association of ALP decline with OS was assessed in the ≤147 U/L and >147 U/L groups separately. Median OS is provided with an unadjusted hazard ratio (HR) (95% confidence interval [CI]). Multivariate Cox models provided adjusted HRs (95% CI) for the association of ALP decline with OS. Some baseline covariates were not included in the models due to missing data. Results: 785 of 1465 pts had baseline ALP measurements, of whom 779 had week 12 ALP measurements: 443 had ≤147 U/L and 336 >147 U/L. In the ≤147 U/L group, median OS was 23.0 months (m) (95% CI 20.9–25.7) in pts with ALP decline (n=329) and 16.4 m (95% CI 14.1–20.4) in pts with no decline (n=114). In the >147 U/L group, median OS was 12.9 m (95% CI 11.7–14.3) in pts with ALP decline (n=295) and 8.1 m (95% CI 5.6–10.3) in pts with no decline (n=41). Comparison of unadjusted and adjusted HRs is shown in the Table. Conclusions: Pts with an ALP decline in first 12 weeks of Ra-223 treatment had longer OS. The effect of other baseline variables, including age, PSA, Hgb and prior treatments, provided adjustment but did not change this outcome. [Table: see text]

3562Background: Bevacizumab is a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, approved in combination with chemotherapy in the treatment of mCRC. It has been hypoth...

11008 Background: Early changes in tumor metabolism measured with positron-emission-tomography/computerized tomography (PET/CT) could predict the long-term efficacy of treatment better than dimensional RECIST response. Methods: We performed PET/CT before and after 1 cycle of treatment in patients with resectable liver metastases from colorectal cancer, within a phase II trial of preoperative FOLFIRI plus bevacizumab. For each lesion, the maximum SUV (SUVmax) and the total lesion glycolisis (TLG) were determined. For both, based on previous studies, a ≤-50% change from baseline was used as threshold for significant response. Metabolic response was categorized no/yes by using three different methods that enter into the calculation (i) the largest observed value (highest SUVmax/TLG), or (ii) the sum of all the observed values (Total SUVmax/TLG), or (iii) each observed values (SUVmax/TLG-by-lesion). Standard RECIST response was assessed after 3 months of treatment. The association between metabolic and RECIST response was tested with the Mc Nemar’s test and their agreement was expressed as Kappa statistics; the ability to predict progression-free (PFS) and overall (OS) survival was tested with Log-rank test and a multivariable Cox model. Results: 33 patients were analyzed. After treatment, there was a notable decrease of all PET/CT parameters, with a median change of -33.9% for the highest SUVmax, -61.5% for the highest TLG, -34.9% for the total SUVmax, and -65.5% for the total TLG. The association of SUV-based metabolic response (but not the TLG-based) with RECIST was statistically significant. However, the agreement between RECIST and PET/CT responses was consistently small. PFS and OS were significantly longer among PET/CT responding patients, whichever the measure used. On the contrary, no significant outcome difference was evident according to RECIST response. Conclusions: Early PET/CT response was significantly predictive of long-term outcomes during preoperative treatment of patients with liver metastases from colorectal cancer and its predictive ability was higher than that of RECIST response. Clinical trial information: 2006-006572-38.

e19034 Background: Targeted therapy against the mutated form of BRAF V600 is a proven effective therapy for melanoma. Objective of this exploratory study was to describe the change over time of PET-scan results and verify the association of PET-scan examination with the objective response (OR) (defined by RECIST criteria) in melanoma pts treated with vemurafenib. These preliminary results reported here regards the description of changes over time of PET-scan. Methods: Patients treated with vemurafenib at our institution were considered eligible. Patients were evaluated with PET-scan at baseline and at day 7, 15 and 30 from the start of therapy. Maximal Standardized Uptake Value (SUVmax) and Total Lesion Glycolysis (mean SUV x lesion volume) were recorded and compared for single lesions in the 4 exams. Differences between each PET-scan performed during therapy and baseline were calculated and coded as yes/no response basing on predefined criteria. Association of PET responses and achievement of OR were estimated by means of logistic regression models. Odds ratio and C statistics were used to define strength of association and discriminant capability. C statistics obtained with PET/CT at different timepoints were compared. Results: As of January 2012, 7 out of 20 required pts have been enrolled. A total of 48 lesions were available for evaluation. A reduction in lesion SUVmax and TLG values compared to baseline was evident in all the post-therapy studies (reduction in SUV max at day 7 – 51 ± 28 %, day 14 – 67 ± 24 % and day 30 –69 ± 29 %, reduction in TLG at day 7 – 41 ± 83 %, day 14 – 69 ± 35 % and day 30 – 68 ± 37 %). A comparison of the day 15 and day 30 studies showed essentially stable uptake values (SUV max variation -3 ± 41 %, TLG 5 ± 56 %). However, 14/23 lesions in 3 patients showed increased SUV max and TLG values between the day 15 and day 30 studies likely indicating early signs of treatment resistance. Conclusions: Our preliminary results suggest that PET/CT may be an early surrogate marker of treatment response to vemurafenib. Sequential monitoring of targeted therapy with PET/CT may be useful in identification of treatment resistance, aid in tailoring alternative strategies and deserves further investigation.

e12502 Background: The extradomain B (ED-B) of fibronectin (FN) is a highly expressed marker of tumor angiogenesis and thus provides a molecular target for radioimmunotherapy (RIT). The RIT agent 1...

8063 Background: The extra-domain A1 (ED-A1) of tenascin-C is a highly expressed component of the tumor extracellular matrix and constitutes a valuable target for radionuclide therapy. Tenarad is a human antibody which is capable of recognizing ED-A1, has been labeled with I-131 and is expressed as small immunoprotein (SIP) for improving its biodistribution properties. Previous phase I/II studies with a similar compound (131I-L19SIP) have shown efficacy in a variety of cancer types. In this ongoing phase I/II trial, Tenarad is administered to patients with progressive Hodgkin lymphoma refractory to conventional treatment. Methods: Eight patients (4 M, 4 F, 19-41 yo) have been enrolled between April and December 2010. All patients had undergone at least three lines of chemotherapy; seven pts had prior external beam radiation therapy and six had prior autologous bone marrow or stem cell transplantation. All patients presented with nodal disease and some had involvement of the bone (n=3), lung (n=2) or liver...

14500 Background: We have previously reported that 3 cycles of Oxaliplatin (OXA), Raltitrexed (TOM) and 5-Fluorouracile (FU) + levo-folinic acid (LFA) during pelvic RT had an acceptable toxicity and produced a complete (TRG1, 42%) or subtotal (TRG2, 29%) pathologic tumor regression in 71% of 31 pts with poor prognosis LARC (Avallone et al, Br J Cancer 2006). Here we report an expanded experience on such treatment. Methods: We enrolled 62 eligible pts (M, 33; F, 29), with median age of 58 (27–79) yrs, and adenocarcinoma of the extraperitoneal rectum, with at least one of the following characteristics: cT4 (N pts), cN+ (N), cT3N0 with tumor location = 5 cm from the anal verge and/or CRM +ve (assessed by MRI) (N). Pts received 3 biweekly courses of OXA 100 mg/sqm + TOM 2.5 mg/sqm on day 1, and LFA 250 mg/sqm + FU 900 mg/sqm (31 pts) or 800 mg/sqm (31 pts) on day 2, and concomitant pelvic RT (1.8 Gy/day, total dose 45 Gy). TME was planned 8 weeks after the end of treatment. Pathologic response was evaluated by tumor regression grading (TRG) according to Mandard’s modified classification. Pts with cT4, pN+ and pCRM +ve received also 4 months of weekly FU/FA. Results: All pts received full dose of RT, and 98% of the planned CT cycles. Neutropenia was the most common grade = 3 toxicity (40%), while grade 3 diarrhea was seen in 19% of pts with FU 900 mg/sqm, and in only 6% of pts with FU 800 mg/sqm. All but 2 pts had a TME with R0 resection, and no treatment-related or perioperative death occurred. Median number of sampled lymph nodes was 36 (range, 10–80). 28 (45%) pts obtained a TRG1, and 17 (27%) pts a TRG2. Activity of the treatment was similar in all risk groups, regardless of FU dosage. 1 pt suffered a local recurrence (after 9 months), and 3 pts had distant metastases (after 22, 33, and 47 months). After a median follow-up of 34 (range 6–54) months, all pts are alive, and the estimated 34-month RFS was 95%. All pts achieving a TRG1, and all but one with TRG2 (pCRM +ve), were recurrence-free. Conclusions: These data confirm the feasibility and activity of the whole treatment. A slight reduction of FU dosage appeared to improve the safety of this combination. Currently, we are now evaluating the addition of bevacizumab 5 mg/kg every 2 weeks before and during this concurrent treatment. No significant financial relationships to disclose.