Significant Differences In TTP Research Articles

Evaluation of Selected MRI Parameters in the Differentiation of Mucinous Ovarian Carcinomas and Metastatic Ovarian Tumors.

Introduction: Analysis of selected MRI parameters in initial MRI for the characterization of ovarian masses enables differentiation between mucinous ovarian carcinoma and metastatic ovarian tumors. Material and Methods: A prospective analysis of contrast-enhanced MRI of patients with suspected ovarian masses diagnosed in ultrasound and CT examination. Morphological criteria, such as the size of lesion, bilateral location, presence of "mille-feuille sign", so-called Seidman criteria, as well as the diffusion weighted imaging and dynamic contrast enhancement of each lesion, were evaluated. Patients were allocated into two groups; the first group contained patients with mucinous ovarian cancer, and the second group contained patients with metastatic ovarian tumors. Results: A total of 35 patients were enrolled into the study. Median age was 49 in the first group and 59 in the second group of patients (p = 0.04). In the first group, all patients (100%) had unilateral lesions, and in the second group, 94% had bilateral tumors (p < 0.000001). In the first group, a tumor size equal or greater than 10 cm was present in 80% of patients, and the same was true for 21% of patients in the second group. The mille-feuille sign was present in 30% of patients from the first group and in 64% of patients from the second group. In the first group of patients, TTP was 410 and Perf.Max Enhancement was 141; in the second group, they were, respectively, 154 and 167 (p = 0.0001 and p = 0.5). Median ADC values in the first group were significantly higher in the first group than in the second group (p < 0.01). Conclusions: Significant differences in TTP and ADC values as well as in Seidman criteria enable reliable differentiation between the analyzed groups of tumors.

Combined early dynamic 18F-FDG PET/CT and conventional whole-body 18F-FDG PET/CT in hepatocellular carcinoma.

To investigate the diagnostic value of early dynamic 18F-FDG PET/CT(ED 18F-FDG PET/CT) combined with conventional whole-body 18F-FDG PET/CT(WB 18F-FDG PET/CT) in hepatocellular carcinoma (HCC), as well as the difference of early dynamic blood flow parameters and maximum standardized uptake value (SUVmax) in HCC patients with/without liver cirrhosis or microvascular invasion (MVI). Twenty-two consecutive patients (mean age 57.8years) with 28 established HCC lesions (mean size 4.5cm) underwent a blood flow study with an 18F-FDG dynamic scan divided into 24 sequences of 5s each and a standard PET/CT scan. On the ED PET/CT study, an experienced PET/CT physician obtained volumes of interest (VOIs) where three blood flow estimates (time to peak [TTP], blood flow [BF], and hepatic perfusion index [HPI]) were calculated. On the WB PET/CT study, a VOI was placed on the fused scan for each HCC and maximum standardized uptake value (SUVmax) was obtained. Comparison of blood flow estimates, SUVmax, and tumor/background ratio (TNR) was performed among HCCs with and without angioinvasion, as well as HCCs in cirrhotic and non-cirrhotic liver. Compared with WB 18F-FDG PET/CT alone, ED combined with WB 18F-FDG PET/CT can significantly increase the detection rate of moderately differentiated and poorly differentiated HCCs (both P < 0.05). HPI was higher in HCCs in patients with liver cirrhosis than those without liver cirrhosis (P = 0.044). There was no significant difference in TTP, BF, SUVmax, or TNR between HCCs in patients with liver cirrhosis and those without liver cirrhosis. There was no significant difference in blood flow estimates or SUVmax in background liver parenchyma between patients with and those without cirrhosis. TTP was shorter in HCCs with MVI than without MVI (P = 0.046). There was no significant difference in BF, HPI, SUVmax, or TNR between HCCs with MVI and without MVI. There was no significant difference in blood flow estimates or SUVmax in background liver parenchyma between patients with and those without MVI. ED combined with WB 18F-FDG PET/CT can significantly increase the detection rate of moderately differentiated and poorly differentiated HCCs. HPI was significantly higher in HCCs in patients with liver cirrhosis than those without liver cirrhosis. TTP was significantly shorter in HCCs with MVI than without MVI.

The Predictive Value of Contrast-Enhanced Ultrasound Combined with Serum miR-124 Level in Acute Cerebral Infarction and Their Correlation with the Contrast Enhancement of Carotid Atherosclerotic Plaque.

ObjectiveTo investigate the predictive value of contrast-enhanced ultrasound (CEUS) combined with serum miR-124 level in acute cerebral infarction (ACI) and their association with the contrast enhancement of carotid atherosclerotic plaque.MethodsTotally 60 patients diagnosed with ACI and 60 controls were included in the study. All the subjects had carotid atherosclerotic plaques, and all of them were examined by CEUS and were tested for serum miR-124 levels.ResultsTime to peak (TTP) and mean transit time (MTT) in the ACI group were significantly shorter than those in the control group (P < 0.05), but the peak intensity ratio (PIR), the area under the curve (AUC), and relative expression levels of serum miR-124 were notably greater in the ACI group (P < 0.05). There were statistically significant differences in TTP, MTT, PIR, AUC, and serum miR-124 expression in patients with different cerebral infarct areas in the ACI group (P < 0.05). Besides, the sensitivity and specificity of serum miR-124 levels for the prediction of ACI were 71.67% and 90.00%, respectively, with a cut-off value of 1.52, and the sensitivity was 86.67% and specificity was 93.33% of CEUS combined with serum miR-124 in the prediction of ACI. The ACI group showed a higher proportion of grades 2 and 3 (P < 0.001). Pearson correlation analysis showed that the intraplaque contrast enhancement was negatively related to TTP and MTT but had a positive correlation with PIR, AUC, and serum miR-124 levels.ConclusionGrades 2 and 3 intraplaque contrast enhancement and serum miR-124 level of 1.52 had high sensitivity and specificity to predict ACI. Moreover, the CEUS parameters combined with serum miR-124 level could improve the performance in predicting ACI and had auxiliary value in evaluating the stability of carotid atherosclerotic plaques.

FDG PET in response evaluation of bulky masses in paediatric Hodgkin’s lymphoma (HL) patients enrolled in the Italian AIEOP-LH2004 trial

We present the results of an investigation of the role of FDG PET in response evaluation of bulky masses in paediatric patients with Hodgkin's lymphoma (HL) enrolled in the Italian AIEOP-LH2004 trial. We analysed data derived from 703 patients (388 male, 315 female; mean age 13years) with HL and enrolled in 41 different Italian centres from March 2004 to September 2012, all treated with the AIEOP-LH2004 protocol. The cohort comprised 309 patients with a bulky mass, of whom 263 were evaluated with FDG PET at baseline and after fourcycles of chemotherapy. Responses were determined according to combined functional and morphological criteria. Patients were followed up for a mean period of 43months and for each child we calculated time-to-progression (TTP) and relapse rates considering clinical monitoring, and instrumental and histological data as the reference standard. Statistical analyses were performed for FDG PET and morphological responses with respect to TTP. Multivariate analysis was used to define independent predictive factors. Overall, response evaluation revealed 238 PET-negative patients (90.5%) and 25 PET-positive patients (9.5%), with a significant difference in TTP between these groups (mean TTP: 32.67months for negative scans, 23.8months for positive scans; p < 0.0001, log-rank test). In the same cohort, computed tomography showed a complete response (CR) in 85 patients (32.3%), progressive disease (PD) in 6 patients (2.3%), and a partial response (PR) in 165 patients (62.7%), with a significant difference in TTP between patients with CR and patients with PD (31.1months and 7.9months, respectively; p < 0.001, log-rank test). Similarly, there was a significant difference in relapse rates between PET-positive and PET-negative patients (p = 0000). In patients with PR, there was also a significant difference in TTP between PET-positive and PET-negative patients (24.6months and 34.9months, respectively; p < 0.0001). In the multivariate analysis with correction for multiple testing, only the PET result was an independent predictive factor in both the entire cohort of patients and the subgroup showing PR on CT (p< 0.01). After fourcycles of chemotherapy, FDG PET response assessment in paediatric HL patients with a bulky mass is a good predictor of TTP and disease outcome. Moreover, in patients with a PR on CT, PET was able to differentiate those with a longer TTP. In paediatric HL patients with a bulky mass and in patients with a PR on CT, response on FDG PET was an independent predictive factor.

HSD3B1 genotype and response to androgen deprivation therapy for biochemical recurrence after radiotherapy for localized prostate cancer.

5050 Background: The enzyme encoded by the HSD3B1(1245C) variant allele has been shown to promote castration-resistant prostate cancer by increasing intratumoral dihydrotestosterone synthesis. In the setting of biochemical recurrence (BCR) following prostatectomy, inheritance of the variant allele has been associated with inferior clinical outcomes for men treated with androgen deprivation therapy (ADT). Whether the same is true in the context of BCR after radiotherapy (RT) is unknown. Methods: We determined HSD3B1 genotype retrospectively in men treated with ADT for post-RT BCR using an established biorepository at a large academic center. We analyzed time-to-progression (TTP), time-to-metastasis (TTM), and overall survival (OS) according to HSD3B1genotype using an additive genetic model with the log-rank trend test. Multivariable analyses (MVA) were performed to adjust for known prognostic factors with Cox regression. Results: We identified 218 men treated with ADT for BCR after RT, of whom 213 (98%) were successfully genotyped (46%, 45% and 9% carrying 0, 1, and 2 variant alleles, respectively). Median follow-up was 7.9 years (yrs). Demographic and treatment factors were similar across genotypes. Median TTP was 2.3 (95% CI: 1.6, 3.1) yrs in men who inherited 0 variant alleles, 2.3 (1.5, 3.3) yrs with 1 variant allele, and 1.4 (0.7, 3.3) yrs with 2 variant alleles (P = 0.683). Median TTM diminished with the number of variant alleles inherited (7.4 [6.7, 9.7], 5.8 [4.9, 6.5] and 4.4 [3.0, 5.7] yrs, respectively (P = 0.030). No difference in OS was detected (P = 0.305). On MVA with 0 variant alleles as the reference, the adjusted hazard ratio (HR) for metastasis was (1.19 [0.74, 1.92]; P = 0.480) for 1 allele and (2.01 [1.02, 3.97]; P = 0.045) for 2 alleles. MVA did not demonstrate significant differences in TTP or OS. Conclusions: The HSD3B1(1245C) allele that enhances dihydrotestosterone synthesis is associated with time-to-metastasis in men treated with ADT for BCR after RT for prostate cancer. Notably, 49% of men had received prior ADT as part of local therapy and 56% received an anti-androgen during ADT for BCR, which may blunt the effect of the variant allele.

The effect of surgery in determining pseudoprogression and predicting outcome in adults with glioblastoma.

2067 Background: Pseudoprogression (PsPD) refers to an increase in size or appearance of new areas of contrast enhancement on MRI scans, seen in about 30% of the patients with newly diagnosed glioblastoma soon after completing chemoradiation (chemoRT). It is distinguished from true progression by its improvement independent of treatment; however, timely diagnosis of PsPD to guide clinical decisions has been a challenge. Given that tissue sampling of the MRI changes, when initially seen, could potentially distinguish PsPD from true progression, we examined the utility of surgery in the diagnosis of PsPD and its impact on patient outcome. Methods: A retrospective review of data from adults with GBM between October 2006 and March 2009 identified 140 patients with MRI changes suggestive of progression within 3 months of chemoRT; of these, 34 underwent surgical resection for diagnostic purposes. Three subsets - progression, PsPD or mixed -were identified based on imaging characteristics in the nonsurgical group and by histology in the surgical group. TTP and OS were calculated using the Kaplan Meier method and log rank analysis for significance of differences. Results: The median TTP was 4.8, 5.8 and 7.5 months (p=0.69) for PsPD, progression and mixed in the surgical group respectively compared to 3.9, 4.1 and 6.2 months (p=0.67) in the nonsurgical group. The median OS was 14.4, 18.5 and 17.1 months (p=0.82) for PsPD, progression and mixed in the surgical group compared to 13.4, 11.6 and 14.5 months (p=0.12) in the nonsurgical group respectively. No significant differences in TTP or OS were seen. Conclusions: These findings suggest that routine surgical sampling and histologic review of MRI changes after chemoRT does not help identify differences in outcome compared to the nonsurgical group. Additionally, no significant differences in outcome were seen among the three categories in the surgical or nonsurgical groups. Refinement of the histological criteria, careful intraoperative selection of areas of interest and advances in imaging studies are critically needed to permit early differentiation of PsPD versus progression to allow appropriate clinical management and formulate prospective studies.

Screening for EGFR Mutations in Patients with Head and Neck Cancer Treated with Gefitinib on a Compassionate-Use Program: A Hellenic Cooperative Oncology Group Study

Background and Aim. EGFR is commonly expressed in cancers of the head and neck (H and N), and anti-EGFR agents have demonstrated improvements in outcomes (TTP and OS). The aim of this study was to determine EGFR gene status in H and N cancer patients treated with gefitinib and to correlate mutational status with clinico-pathological data and response. Patients and Methods. Patients with histologically confirmed H and N cancer having failed prior treatment for advanced disease entered this compassionate-use-program. Nineteen patients received gefitinib. EGFR expression was assessed by IHC, gene copy number by FISH, and mutation analysis was conducted for EGFR (18-21), KRAS, BRAF (V600E), and HER-2 exon 20. An additional TKI naive cohort of 73 patients was also screened. Results. Mutations were detected in 6/19 patients (3× EGFR, 1× KRAS, and 2× HER2-exon 20). There were no significant differences in TTP or OS for patients with somatic EGFR mutations. No BRAF mutations were detected. Conclusions. The incidence of EGFR mutations in H and N cancer in this study was 5.3%. No statistically relevant correlations between mutation or gene gain and response or survival were observed. Due to the limited number of patients and low incidence of genetic aberrations in the genes analyzed, additional studies are warranted.

Gain(1)(q21) Defines Group of Newly Diagnosed Multiple Myeloma Patients with Poor Prognosis.

Abstract 2820Poster Board II-796The presence of chromosomal abnormalities detected by FISH in plasma cells is considered to be an important prognostic factor for patients with multiple myeloma. In this study we analysed the impact of gain(1)(q21), del(13)(q14), del(17)(p13), t(4;14) and (non)hyperdiploidy on prognosis in MM patients. Taking together 194 MM patients (median age 66 years) were successfully examined by FISH for presence of above named chromosomal abnormalities in plasma cells. A total of 47 patients (median follow-up 43.2 months; 91% first line treatment, 9% second line treatment) were treated by peripheral blood stem cells transplantation (PBSCT). A total of 86 patients (median follow-up 38.4 months; 38% first line treatment, 43% second line treatment, 19% >2 previous treatment lines) were treated by thalidomide based regimen (86% together with glucocorticoids and alkylating agens). A total of 61 patients (median follow-up 46.5 months; 16% first line treatment, 36% second line treatment, 33% third line treatment, 15% >3 previous treatment lines) were treated by bortezomib based regimen (53% with glucocorticoids and alkylating agens, 20% with glucocorticoids + anthracycline). Gain(1)(q21) was found in 52% (101/194), del(13)(q14) in 55% (69/125), del(17)(p13) in 12% (13/112), t(4;14) in 20% (18/90) and 44% (56/126) of cases were hyperdiploid. In any of the three treatment based groups of patients we haven't found any significant difference in TTP, OS and treatment response (ORR) between any studied positive/negative chromosomal abnormality except gain(1)(q21). See Table 1 for results overview (TTP only). In patients treated by PBSCT (regardless of their pre-treatment) significant difference in TTP and OS for positive/negative patients was observed (15.6 vs. 27.3 months, p=0.002 for TTP; 47.2 vs. NR months, p=0.001 for OS). Furthermore, we entirely focused on newly diagnosed patients divided them into three subgroups: (1) patients treated by PBSCT in first line (n=42), (2) patients treated by thalidomide based regimen in first line (n=33) and (3) patients treated by bortezomib based regimen in first line (n=10). We confirmed unfavourable impact of gain(1)(q21) in patients treated with PBSCT whereas TTP and OS in gain(1)(q21) positive/negative patients was 15.6 vs. 27.3 months, p=0.003 (TTP); 47.2 vs. 66.9 months, p=0.002 (OS). This difference in TTP/OS among gain(1)(q21) positive/negative patients was observed neither in thalidomide based subgroup [NR vs. 11.7 months, p=0.956 (TTP); NR vs. 34.4 months, p=0.683 (OS)] nor in bortezomib based subgroup [(8.5 vs. 6.5 months, p=0.549 (TTP); NR vs. 6.8, p=0.254 (OS)]. See Table 2 for results overview (TTP only). In this study we revealed gain(1)(q21) almost in one half of MM cases, and we defined the newly diagnosed MM patients carrying gain(1)(q21) as a unique group of patients with poor prognosis. Nevertheless, treatment based on bortezomib / thalidomide combination probably suppresses unfavourable prognostic impact of all studied chromosomal abnormalities including gain(1)(q21). This study was supported by grant LC06027 of Masaryk University, Brno, Czech Republic, and by grants MSM0021622415 and MSM0021622434 of Ministry of Education, Czech Republic, and by IGA grants NR/9317-3 and NS/10207-3/2009 of Ministry of Medicine, Czech Republic. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Lenalidomide Plus Dexamethasone Versus Lenalidomide Plus Melphalan and Prednisone: A Case-Control Study in Newly Diagnosed Elderly Myeloma Patients.

Abstract 2877Poster Board II-853 Background and Objective:In newly diagnosed multiple myeloma (MM) patients, treatment with lenalidomide plus high-dose dexamethasone (RD) was superior to high-dose dexamethasone in terms of both response rates and 1-year progression-free survival (PFS) (Zonder JA et al, Blood 2007;110:77). Preliminary results suggest that the combination lenalidomide plus low-dose dexamethasone (Rd) compared to the RD regimen yields significantly better 2-year overall survival (OS) (Rajkumar SV et al, J Clin Oncol 2008;26:8504). The combination of melphalan, prednisone, and lenalidomide (MPR) has been investigated in a phase I/II study showing promising results (Palumbo A et al, J Clin Oncol 2007; 25:4459-4465). The goal of this case –control study was to compare the efficacy and the toxicity of the lenalidomide/dexamethasone (len/dex) combination vs MPR as primary therapy for newly diagnosed elderly MM patients, to determine the additive value of melphalan compared to a regimen of lenalidomide plus corticosteroid. Patients and methods:Data from 51 newly diagnosed MM patients enrolled in Italy in a phase I/II dose-escalating trial, from January to October 2005, with MPR, were analyzed. For comparison of their outcome, 37 patients were identified among newly diagnosed patients seen at the Mayo Clinic from March 2005 to December 2008 who received len/dex as primary therapy and were enrolled in phase II or III trials. Patients treated with MPR received 9 monthly cycles of oral melphalan (doses ranging from 0.18 to 0.25 mg/kg on days 1-4), prednisone (2 mg/kg on days 1-4) and lenalidomide (doses ranging from 5 to 10 mg/day on days 1-21). After 9 cycles, patients started maintenance with lenalidomide alone (10 mg, days 1-21) until relapse or progression. Patients treated with len/dex received oral lenalidomide (25 mg/day, days 1-21) plus dexamethasone, either at low-dose (n=17) (40 mg orally days 1, 8, 15, 22) or at high-dose (n=21) (40 mg orally on days 1-4, 9-12, and 17-20). Treatment was continued until progression, relapse or unacceptable toxicity, or could be stopped at the physician's discretion. Patients (n=13) were allowed to receive transplant if they wished and were deemed eligible. Outcome was analyzed on an intention-to-treat basis. The Chi-square or the rank sum tests were used to compare variables. Time-to-event analysis was performed using the Kaplan-Meier method and comparisons were determined by the log-rank test and the Cox proportional hazards model. Results:On intention-to-treat analysis, 15.7% versus 23.7% patients, respectively in the MPR and in the len/dex group, (p=0.342) achieved a complete response, and 43.2% vs 47.4%, (p=0.691) achieved at least a very good partial response. Time-to-progression (TTP) (median: 24.7 vs 27.5 in MPR and len/dex groups, respectively; HR 1.04; 95% CI 0.55-1.98; p=0.903), PFS (median: 24.7 vs 27.5 in MPR and len/dex groups, respectively; HR 1.03; 95% CI 0.55-1.92; p=0.926) and OS (2-year OS: 86.2% in MPR group vs 89.1% in len/dex, HR 0.86; 95% CI 0.38-1.98; p=0.730) were not significantly different between the 2 groups. No significant differences in TTP, PFS and OS were reported when MPR patients were compared with the subgroup of patients treated with low-dose dexamethasone plus lenalidomide. Similar results were found when the analysis was restricted to MPR patients and len/dex pair mates receiving lenalidomide plus low/dose dexamethasone, matched according to age and sex, and who did not received transplant. The toxicity profile was different in the two groups. Hematologic grade 3-4 toxicities were more common with MPR compared with len/dex, in particular neutropenia (66.7% vs 21.1%, p < 0.001) and thrombocytopenia (31.4% vs 2.6%, p < 0.001), respectively. Grade 3-4 gastrointestinal events (13.2% vs 2.0%, p= 0.080), thrombotic events (13.2 vs 5.9, p= 0.279) and fatigue (10.5% vs 3.9%, p= 0.395) were more common with len/dex compared with MPR. Conclusion:Results of this case-control study show that both MPR and Rd are efficacious regimens for elderly MM patients. Data need however to be carefully evaluated and randomized control trials are needed to confirm these results. Disclosures:Off Label Use: research drug in combination to standard of care. Kumar:celgene: Research Funding; millenium: Research Funding; bayer: Research Funding; novartis: Research Funding; genzyme: Research Funding. Dispenzieri:celgene: Research Funding. Gertz:celgene: Honoraria; genzyme: Honoraria; millenium: Honoraria; amgen: Honoraria. Lacy:celgene: Research Funding. Musto:celgene: Honoraria. Fonseca:medtronic: Consultancy; genzyme: Consultancy; celgene: Consultancy; amgen: Consultancy; BMS: Consultancy; otsuka: Consultancy. Petrucci:celgene: Honoraria; Janssen Cilag: Honoraria. Greipp:celgene: Research Funding. Boccadoro:jansen Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; pharmion: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Palumbo:Janssen-Cilag: Honoraria; Celgene: Honoraria.

Phase II trial of erlotinib maintenance therapy after platinun-based chemotherapy in advanced non-small cell lung cancer (NSCLC)

e19013 Background: phase II trial-efficacy &amp; toxicity of sequential erlotinib in advanced NSCLC after platinum-based CT Methods: Pts with adv NSCLC, PS 0/1, adequate renal, hepatic and bone marrow function, no PD after CT. Treatment: erlotinib 150 mg/day starting 3–4 weeks after CT until progression. Safety was evaluated monthly and tumor evaluation bimonthly. Results: 47 pts enrrolled:42(89%)stageIV &amp; 5(11%)wet IIIB, all valid for response &amp; toxicity. Median age 62 y(r:39 -77): 39(83%) males and 8(17%) females. Histology: adenocarcinoma 8(61.7%), bronquioloalveolar 3(6.4%), large cell 3(6.4%), squamous12(25.5%). PS 0: 23(49%), PS 1:24(51%). 38(81.9%) completed 6 cycles of CT. Response: CR: 1(2.1%), PR: 2(51.1%), EE: 22 (46%). Sequential erlotinib improved RR in 6 (12.8%), 23 (48.9) prolonged stabilization, 18 (38.3%) had progression. Median TTP and OS were 9.4 m (95% CI, 4.96–13–84), and 19.23 m (95% CI, 8.82–29.64). No significant differences in TTP according to age, sex, PS, histology or previous response to CT, but yes depending on RR to erlotinib: PR: 31.5 m (95% CI 15.37–47.63), EE: 12.8 m (95% CI, 10.58–15.03), PD: 6.3 m (95% CI, 5.36–7.3), p &lt; 0.001; and moreover depending on smoking status: Never: 21.67 m(95% CI, 5.39–37.94), previous smoker &gt; 5 years: 14.03 m(95% CI, 10.77–17.30), previous smoker 1 year: 7.77 m(95% CI, 7.62–7.91), current smoker: 5.9 m(95% CI, 5.12–6.34), p &lt;0.001. In Cox-regression model, smoking status ( p&lt; 0.001), and response to erlotinib (p=0.002) were associated with a significant difference in TTP. Similar results in OS, although in Cox-regression model only never smoker or &gt; 5 years previous smoker pts had a significant better survival. Toxicity: The most frequent was skin rash, grade (g) 1 in 11(23.4%), g 2: 16(34%) and g 3: 3(6.4%). Only 1 p had diarrea g 3, and no other side effects were observed. We found a significant benefit in p with g 2–3 skin toxicity respect g 0–1, in both TTP( p= 0.0003) and OS (p= 0.0014). Conclusions: Erlotinib-maintenance therapy after platinum-based CT had promising results. Pts with the best benefit were those with response to erlotinib, in never or past (&gt; 5 years) smokers and with g 2–3 skin toxicity. No significant financial relationships to disclose.

Adult Tetralogy of Fallot

To determine the potential role of dynamic temporally resolved three dimensional (3D) contrast-enhanced magnetic resonance angiography (MRA) for quantitative evaluation of pulmonary perfusion in adult patients with surgically treated Tetralogy of Fallot (ToF). Institutional review board approval and written informed consent were obtained for this Health Insurance Portability and Accountability Act-compliant study. Thirty consecutive patients with surgically repaired ToF and 30 age-matched controls underwent breath-hold 3D time-resolved MRA (TR-MRA) and single-phase high-resolution 3D MRA of the thorax at 1.5 T. Two readers evaluated both datasets for image quality and findings. On TR-MRA datasets, regions-of-interest were placed over main pulmonary artery and lung fields obtaining signal intensity time curves. Using analytic software, time-to-peak (TTP), mean transit time (MTT), maximal signal intensity (MSI), maximum upslope of the curve (MUS), pulmonary blood volume (PBV), and pulmonary blood flow (PBF) were calculated. Pulmonary radionuclide scintigraphy was available for a subgroup of patients with ToF (n = 12). For ToF patients with unilateral pulmonary artery (PA) stenosis, TTP, and MTT were significantly longer, and MSI, MUS, PBV, and PBF were significantly lower in the ipsilateral lung compared with control subjects (P < 0.001 for all). There was no significant difference in TTP, MTT, MSI, MUS, PBV, and PBF between ToF patients without postsurgical stenotic residua and control subjects (P > 0.05 for all), nor between the mentioned perfusion indices for the contralateral lung in ToF patients with unilateral PA stenosis and control subjects (P > 0.05 for all). In ToF, patient with unilateral PA stenosis, analysis of contralateral-to-ipsilateral lung perfusion ratios on radionuclide scintigraphy and TR-MRA revealed significant correlation (r = 0.96). Bland-Altman plot showed a mean difference of 2.2% between the measured ratios (limits of agreement; -7.6%-12.0%). Time-resolved 3D contrast-enhanced MRA has potential for noninvasive and quantitative assessment of altered patterns of pulmonary perfusion in adult ToF, and may be a reliable technique for evaluation of postsurgical residua in these patients.

A Placebo-Controlled Phase III Trial of Patient-Specific Immunotherapy with Mitumprotimut-T (ID-KLH) and GM-CSF Following Rituximab in Patients with CD20+ Follicular Lymphoma

Background: Early studies demonstrated that patients with indolent B-cell lymphomas have the capacity to mount anti-idiotype (Id) B-cell immune responses following active immunization with patient-specific Id proteins. Durable clinical remissions were observed in patients undergoing vaccination in chemotherapy-induced first remissions. This study evaluated the efficacy and safety of active immunotherapy with mitumprotimut-T (Id- KLH, SPECIFID™, Favrille, San Diego, CA) and GM-CSF (sargramostim, LEUKINE®) in patients with CD20+ follicular lymphoma. Mitumprotimut-T is a patient-specific therapeutic vaccine composed of the Id protein produced by proprietary recombinant technology from the malignant lymphoma biopsy specimen and conjugated to KLH, a potent immunogenic protein.Patients and Methods: Patients with treatment-naïve (T-N) or relapsed/refractory (R/R) WHO Grade 1–3 CD20+ follicular lymphoma received rituximab infusions at 375 mg/m2 weekly for 4 weeks, and those achieving a complete response (CR), partial response (PR), or stable disease (SD) at Week 11 were randomized to mitumprotimut-T (1 mg subcutaneously on Day 1) and GM-CSF (250 mcg subcutaneously daily on Days 1–4) or placebo and GM-CSF. Randomization was stratified by prior therapy (T-N vs. R/R) and response to rituximab (CR/PR vs. SD). Patients were immunized monthly × 6, every other month × 6, and then every 3 months until disease progression (PD). The primary efficacy endpoint was time-to-progression (TTP), which was assessed by an independent central radiology review.Results: 349 patients were randomized; their median age was 54 years (range, 21–86 years), 79% were T-N, 85% had an ECOG performance status of 0, and 86% had Stage III-IV disease. Thirty-four randomized patients (10%) did not receive blinded study drug: 28 because mitumprotimut-T could not be produced, 5 due to PD prior to start of blinded study drug, and 1 who withdrew for personal reasons. The mean number of courses was 10.6 (range, 1–21), and was comparable in the 2 groups. After a median follow-up of 40 months, 215 patients (62%) had progressed, 113 who were randomized to mitumprotimut-T and 102 who had received placebo. Median TTP from randomization was 9.0 months for patients randomized to mitumprotimut-T/GM-CSF and 12.6 months for placebo/GM-CSF (hazard ratio = 1.384, p = 0.019). Significantly more patients with high-risk FLIPI and fewer patients with low-risk FLIPI were unexpectedly randomized to mitumprotimut-T (p = 0.0042). After adjusting for FLIPI risk group in a Cox regression model, there was no significant difference in TTP between the two arms in the intent-to-treat population (p = 0.128), in patients with high risk FLIPI (p = 0.891), in patients with intermediate/low risk FLIPI (p = 0.143), in the 315 patients treated with blinded study drug, or in any of the patient subsets based on stratification factors. Comparisons of TTP between the two treatment arms using the investigators assessment of response were consistent with those obtained from central radiology review. There were no significant differences between the two treatment arms in objective responses (CR+PR) to rituximab at Week 11 (57.6%, combined data from both arms) or in objective responses any time on study (64.7%, combined data). Treatment was usually well tolerated, with 76% of adverse events graded as mild or moderate. The most common side effect was local injection site reaction, reported in 94% of patients.Conclusion: This Phase 3 trial showed no improvement in TTP with mitumprotimut-T and GM-CSF following rituximab in CD20+ follicular lymphoma.

Use of C-terminal deletion mutation of CD20 molecule to predict CD20 expression and time to progression after rituximab in non- Hodgkin lymphoma

8088 Background: Rituximab was the first chimeric antibody that is most frequently used for CD20-posistive B-cell lymphomas and gives better response and prognosis. However, resistance to rituximab is one of the important issues to be clarified in the increasing number of monoclonal antibody therapy, and we experienced the case whose lymphoma cells never expressed CD20 at the relapsed phase during rithuximab therapy. We investigated whether CD20 mutation is related to expression level of CD20, relapse or resistance to rituximab therapy, and prognosis. Methods: We analyzed 50 patients with fresh or relapsed/resistant B- cell lymphomas and DNA sequencing analysis of CD20 products from genomic PCR and RT-PCR was performed. CD20 mutants were subcloned by TA cloning, and tested CD20 expression after transfection to K562 cells. Results: Four types of CD20 mutations were found in 11 of 50 NHL patients (22.0%), which include C- terminal deletion (8.0%) extracellular domain (2.0%) transmembrane domain (2.0%) and early termination (10.0%). The group of C-terminal deletion mutations significantly showed lower CD20 expression (3.26, 95%CI = 0.09 to 6.89) than non-mutation (30.8, 95%CI = 22.4 to 39.2) (p 0.05). Although there was no significant difference between the groups with non-mutation and C-terminal deletion mutation in CR rate (49% versus 25%, Fisher's exact test; p = 0.6137), time to progression after rituximab therapy in C-terminal deletion mutation (7 months, 95%CI = 0 to 18 months) was significantly shorter than that in non-mutation (31 months, 95% CI = 18 to 44 months) by log-rank test (p = 0.0481). Non-mutation and early termination groups did not show any significant differences in TTP and CD20 expression. Conclusion: The important mutations of CD20 gene related to shorter duration to progression disease after rituximab therapy were discovered. Especially, point mutations bearing during rituximab therapy should be examined at progression disease after partial remission. No significant financial relationships to disclose.

Contrast ultrasound perfusion imaging of lower extremities in peripheral arterial disease: a novel diagnostic method

The purpose of this study was to establish contrast-enhanced ultrasound perfusion imaging (CUPI) of the lower extremities as a novel non-invasive diagnostic tool for patients with peripheral arterial disease (PAD). Ultrasound contrast agent (SonoVue) was injected into a peripheral vein of 16 control subjects and 16 PAD patients and its appearance in the calf muscle was detected by low-energy harmonic ultrasound. Analysis of the wash-in curves revealed that PAD patients had a significantly longer time to peak intensity (TTP), i.e. duration of maximum contrast perfusion [37 s (19-79 s) in control subjects vs. 56 s (32-104 s) in PAD patients at rest, age-adjusted P=0.002]. Exercise stress test of the calf muscle resulted in a decrease of the TTP, maintaining the significant difference in TTP between the groups [19 s (8-37 s) in control subjects vs. 32 s (18-48 s) in PAD patients after exercise, age-adjusted P=0.004]. Neither ankle-brachial index and TTP nor age and TTP showed a significant correlation. CUPI reflects the regional blood circulation of the calf muscle. In this pilot study, PAD patients show a significantly longer TTP than control subjects. The clinical relevance of CUPI is topic of ongoing studies.

Phenotype-genotype correlation in haemoglobin H disease in childhood.

In this study we used restriction endonuclease mapping to characterise the molecular defect responsible for haemoglobin H disease in 14 Sardinian children. The resulting genotypes were then correlated with the...