Significant Difference In mOS Research Articles

Outcome with Intensive Chemotherapy Compared to Hypomethylating Agent- Based Induction in Patients Aged 70 Years or Older with Newly Diagnosed Favorable Risk Acute Myeloid Leukemia

Outcome with Intensive Chemotherapy Compared to Hypomethylating Agent- Based Induction in Patients Aged 70 Years or Older with Newly Diagnosed Favorable Risk Acute Myeloid Leukemia

Value and significance of brain radiation therapy during first-line EGFR-TKI treatment in lung adenocarcinoma with EGFR sensitive mutation and synchronous brain metastasis: Appropriate timing and technique.

BackgroundFor lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) sensitive mutation and synchronous brain metastasis (syn‐BM), when and how to apply radiotherapy (RT) during first‐line tyrosine kinase inhibitor (TKI) treatment remains debatable.MethodsFrom a real‐world multicenter database, EGFR‐mutant patients with syn‐BM diagnosed between 2010–2020 and treated with first‐line TKIs were enrolled and divided into upfront TKI + RT and upfront TKI groups. Median intracranial progression‐free survival (mIC‐PFS), median overall survival (mOS), and their risk factors were estimated.ResultsThere were 60 and 186 patients in the upfront TKI + RT group and upfront TKI group, respectively. Their mIC‐PFS were 28.9 months (m) and 17.5 m (p = 0.023), and mOS were 42.7 m and 40.1 m (p = 0.51). Upfront brain RT improved mIC‐PFS in patients ≤60‐year‐old (p = 0.035), with symptomatic BM (p = 0.002), and treated with first‐generation TKIs (p = 0.012). There was no significant difference in mOS in any subgroup. Upfront brain stereotactic radiosurgery (SRS) showed a trend of better mIC‐PFS and mOS. mIC‐PFS was independently correlated with symptomatic BM (HR = 1.54, p = 0.030), EGFR L858R mutation (HR = 1.57, p = 0.019), and upfront brain RT (HR = 0.47, p = 0.001). mOS was independently correlated with being female (HR = 0.54, p = 0.007), ECOG 3–4 (HR = 10.47, p < 0.001), BM number>3 (HR = 2.19, p = 0.002), and third‐generation TKI (HR = 0.54, p = 0.044) or antiangiogenic drugs (HR = 0.11, p = 0.005) as first/second‐line therapy.ConclusionsUpfront brain RT based on first‐line EGFR‐TKI might improve IC‐PFS but not OS in EGFR‐mutant lung adenocarcinoma patients, indicating potential survival benefit from brain SRS and early application of drugs with higher intracranial activity.

Correlation of circulating tumor DNA EGFR mutation levels with clinical outcomes in patients with advanced lung adenocarcinoma

Background:Circulating tumor DNA (ctDNA) is a promising biomarker for non-invasive epidermal growth factor receptor mutations (EGFRm) detection in lung cancer patients, but existing methods have limitations in sensitivity and availability. In this study, we used the ΔCt value (mutant cycle threshold [Ct] value–internal control Ct value) generated during the polymerase chain reaction (PCR) assay to convert super-amplification-refractory mutation system (superARMS) from a qualitative method to a semi-quantitative method named reformed-superARMS (R-superARMS), and evaluated its performance in detecting EGFRm in plasma ctDNA in patients with advanced lung adenocarcinoma.Methods:A total of 41 pairs of tissues and plasma samples were obtained from lung adenocarcinoma patients who had known EGFRm in tumor tissue and were previously untreated. EGFRm in ctDNA was identified by using superARMS. Through making use of ΔCt value generated during the detection process of superARMS, we indirectly transform this qualitative detection method into a semi-quantitative PCR detection method, named R-superARMS. Both qualitative and quantitative analyses of the data were performed. Kaplan–Meier analysis was performed to estimate the progression-free survival (PFS) and overall survival (OS). Fisher exact test was used for categorical variables.Results:The concordance rate of EGFRm in tumor tissues and matched plasma samples was 68.3% (28/41). At baseline, EGFRm-positive patients were divided into two groups according to the cut-off ΔCt value of EGFRm set at 8.11. A significant difference in the median OS (mOS) between the two groups was observed (EGFRm ΔCt ≤8.11 vs. >8.11: not reached vs. 11.0 months; log-rank P = 0.024). Patients were divided into mutation clearance (MC) group and mutation incomplete clearance (MIC) group according to whether the ΔCt value of EGFRm test turned negative after 1 month of treatment. We found that there was also a significant difference in mOS (not reached vs. 10.4 months; log-rank P = 0.021) between MC group and MIC group. Although there was no significant difference in PFS between the two groups, the two curves were separated and the PFS of MC group tended to be higher than the MIC group (not reached vs. 27.5 months; log-rank P = 0.088). Furthermore, EGFRm-positive patients were divided into two groups according to the cut-off of the changes in ΔCt value of EGFRm after 1 month of treatment, which was set at 4.89. A significant difference in the mOS between the two groups was observed (change value of ΔCt >4.89 vs. ≤4.89: not reached vs. 11.0 months; log-rank P = 0.014).Conclusions:Detecting EGFRm in ctDNA using R-superARMS can identify patients who are more likely sensitive to targeted therapy, reflect the molecular load of patients, and predict the therapeutic efficacy and clinical outcomes of patients.

Treatment outcomes of recurrent and metastatic adenoid cystic carcinoma: A retrospective analysis.

e18056 Background: Adenoid cystic carcinoma (ACC) is a rare malignancy of glandular tissue with a high rate of local recurrence and metastatic disease. Despite being regarded as an indolent disease, the clinical course of recurrent and metastatic ACC (R/M ACC) is highly variable. Responses to chemotherapy (chemo) are uniformly poor. Several multi-targeted tyrosine-kinase inhibitors (mTKIs), EGFR inhibitors (EGFRi) and other targeted agents have been studied in single-arm early phase trials with response rates ranging from 0-16% and progression free survival ranging from 2.5-17 months. However, there have been no comparative clinical trials and it is not known if one treatment strategy is superior. We undertook this retrospective study to assess the real-world clinical outcomes in patients with adenoid cystic carcinoma using the Caris Life Sciences database. Methods: Real world overall survival (rwOS) for cases of ACC was obtained from insurance claims data and Kaplan-Meier estimates were calculated from the date of collection to the date of last contact. Cases were divided into subgroups based on treatment received – chemo (including platinum agents, taxanes, 5FU, topoisomerase inhibitors, anthracyclines), EGFRi (cetuximab, erlotinib, lapatinib), mTKIs (pazopanib, axitinib, sunitinib, cabozantinib, lenvatinib, sorafenib) and immune checkpoint inhibitors (ICIs) (atezolizumab, ipilimumab, pembrolizumab, nivolumab). Results: 368 patients (pts) were identified with ACC, 16 were locally recurrent and 216 tumors were taken from metastatic sites. 50 pts received chemo, 6 were treated with EGFRi and 15 with mTKIs. Pts who received combination EGFRi and chemo or mTKI and chemo were excluded. The median overall survival (mOS) all patients with metastatic ACC was 2.8 years (yrs). The mOS of pts with R/M ACC was 3 yrs for chemo, 2.9 yrs for EGFRi and 1.5 yrs for mTKIs. There was no significance in mOS between chemo vs mTKIs (HR 0.85, 95% CI 0.3 - 2, p = 0.72) and chemo vs EGFRi (HR = 0.88, 95% CI 0.3 - 2.5, p = 0.78). We further compared the outcomes of those treated with EGFRi (n = 8) with mTKIs (n = 19) in the entire cohort. For most pts, these agents were given as front line therapy. 25% (2/8) of patients had received treatment prior to EGFRi and 20% (4/9) prior to mTKIs (p = 1). There was no significant difference in mOS with HR 0.6 (95% CI 0.16 - 2.6), p = 0.6. We also compared the mOS of patients who received ICIs (n = 22) with those who did not (n = 346) but there was no significant difference (mOS 3.19 vs 3.17 yrs respectively, HR 0.87, 95% CI 0.47- 1.61, p = 0.65). Conclusions: There was no significant difference in the mOS between pts with R/M ACC who were treated with chemo, EGFRi or TKIs and in those who received ICIs compared to those who did not in our limited patient population. This highlights the need for predictive biomarkers for better patient selection with the goal of personalizing treatment strategies for this disease.

Continuous Low-Dose Apatinib Combined With WBRT Significantly Reduces Peritumoral Edema and Enhances the Efficacy of Symptomatic Multiple Brain Metastases in NSCLC.

Background:Symptomatic multiple brain metastases with peritumoral brain edema (PTBE) occur in non-small cell lung cancer patients (NSCLC) who are without driver mutations or are resistant to epidermal growth factor tyrosine kinase (EGFR-TKI) are often associated with an unfavorable prognosis. Whole brain radiation therapy (WBRT) which comes with many complications and unsatisfactory effects, is the only option for the treatment. Previous studies have shown that bevacizumab can reduce the volume of PTBE and improve efficiency of radiotherapy. This study evaluated the effects and safety of apatinib combined with WBRT in NSCLC patients with symptomatic multiple brain metastases and PTBE.Methods:We performed a retrospective review of 34 patients with symptomatic multiple brain metastases from NSCLC (number >4, and at least 1 measurable brain metastasis lesion with cerebral edema). Intracranial objective response rate (IORR), peritumoral edema and intracranial tumor volumetric measurement, Karnofsky performance status (KPS) and adverse events (AEs) were evaluated. Median intracranial progression-free survival (mIPFS) and median overall survival (mOS) were also analyzed.Results:Thirteen cases received apatinib (125 mg or 250 mg, QD, oral) combined with WBRT and 21 cases received chemotherapy combined with WBRT were inclued. Apatinib combination group can better reduce the volume of intracranial tumors and PTBE and total steroid dosage used. It was associated with a better IORR (84.6% vs 47.6%, P = 0.067), longer mIPFS (6.97 vs 4.77months; P = 0.014). There was no significant difference in mOS(7.70 vs 6.67 months; P = 0.14) between the 2 groups. The most common adverse events of apatinib combination WBRT included grade 1/2 nausea (4/13), fatigue (3/13), hypertension (2/13) and white blood cell decrease (2/13). No grade 3/4 AEs were observed.Conclusion:Apatinib plus WBRT is well tolerated and may be a potential choice for relapsed or drug-resistant advanced NSCLC patients with symptomatic multiple brain metastases and PTBE.

Abstract LB-153: Prognostic value of PD-L1 expression on tumor-infiltrating immune cells in renal cell carcinoma (ARCHERY study)

Abstract Background: The correlation between PD-L1 expression on tumor-infiltrating immune cells and prognosis in renal cell carcinoma (RCC) has been reported in several studies. Methods: A multicenter retrospective study was carried out to investigate the prognostic value of PD-L1 expression (by the VENTANA SP142 immune cell [IC] scoring method) in primary RCC tumors among patients administered systemic therapy for recurrent or metastatic RCC. The primary endpoint was overall survival (OS), defined as the time from the initiation of first-line treatment to the date of death from any cause. The difference in OS between patients of positive PD-L1 status (IC ≥1%) and those of negative status was compared using a stratified log-rank test at a two-sided level of 0.1, stratified by MSKCC risk and liver metastases. Stratified hazard ratio (HR) and its 90% confidence interval (CI) was estimated by the Cox proportional hazard model. An unstratified analysis and an analysis adjusted by propensity score weighting (PSW) were also conducted. Results: We examined 777 RCC surgical specimens, 770 of which were included for primary analysis (7 were excluded owing to indeterminate PD-L1 status). PD-L1 positive was observed in 315 (40.9%). Immune phenotype that describe the level of T-cell presence and activity within the tumor microenvironment differed between PD-L1-positive vs. -negative groups: Excluded (74.3% vs. 31.6%), Inflamed (16.5% vs. 1.5%), and Desert (9.2% vs. 66.8%). PD-L1-positive status was more common in patients with higher clinical stage, higher Fuhrman grade, and presence of sarcomatoid component. A higher proportion of PD-L1-positive patients had poor prognostic features at the start of first-line therapy: 17.5% vs. 7.3% with ‘poor' MSKCC risk; 29.2% vs. 14.9% with ‘poor' IMDC risk. In line with this, fewer PD-L1-positive patients had good prognostic features at the start of first-line therapy: 11.4% vs. 29.7% with ‘favorable' MSKCC risk; 10.8% vs. 26.2% with ‘favorable' IMDC risk.The median OS in PD-L1-positive vs. -negative patients was 30.9 months (95%CI: 25.5-35.7) vs. 37.5 months (95%CI: 34.0-42.6). The stratified HR was 1.04 (90%CI: 0.89-1.22, P=0.65), the unstratified HR was 1.21 (90%CI: 1.04-1.40), and the PSW-adjusted HR was 0.99. Subgroup analysis based on MSKCC risk at the start of first-line therapy revealed that there was no significant difference in mOS based on PD-L1-positive vs. -negative status for ‘favorable' (58.6 vs. 59.8 months; HR: 0.92; 95%CI: 0.54-1.56), ‘intermediate' (31.6 vs. 33.5; HR: 1.06; 95%CI: 0.85-1.32) or ‘poor' (6.6 vs 12.8.; HR: 0.89; 95%CI: 0.55-1.43) categories. Conclusion: This study suggested that PD-L1 status on tumor-infiltrating immune cells was not an independent prognostic factor in recurrent or metastatic RCC patients, although positive PD-L1 status was associated with poor prognostic factors. Citation Format: Hirotsugu Uemura, Motohide Uemura, Naoto Sassa, Noboru Nakaigawa, Katsunori Tatsugami, Kenichi Harada, Toshinari Yamasaki, Nobuaki Matsubara, Tamaki Fukuyama, Takuya Yoshimoto, Yuki Nakagawa, Mototsugu Oya, Nobuo Shinohara, Toyonori Tsuzuki. Prognostic value of PD-L1 expression on tumor-infiltrating immune cells in renal cell carcinoma (ARCHERY study) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-153.

Outcomes of Patients with Relapsed or Refractory Acute Myeloid Leukemia Receiving Hypomethylating Agent and Venetoclax

Outcomes of Patients with Relapsed or Refractory Acute Myeloid Leukemia Receiving Hypomethylating Agent and Venetoclax

651P - Obese and overweight is associated with better prognosis in metastatic colorectal cancer patients treated with bevacizumab

BackgroundPrevious studies showed that high and low body mass index (BMI) is associated with worse prognosis in early-stage colorectal cancer (CRC), and low BMI is associated with worse prognosis in metastatic CRC (mCRC). Whether BMI is a prognostic or predictive factor in patients with mCRC is unclear. The aim of the study was to assess the efficacy outcomes according to BMI range in patients with mCRC treated with bevacizumab plus FOLFOX (oxaliplatin, 5-fluorouracyl, folinic acid) chemotherapy regimen. MethodsThe analysis included patients with mCRC receiving bevacizumab plus FOLFOX in the second line treatment. Patients were divided into three study groups according to BMI range: >30kg/m2 (obese patients), ≥ 25 - < 30kg/m2 (overweight patients), <25 (normal weight patients). The median PFS (progression-free survival) and OS (overall survival) of the treated patients was compared based on the BMI range. Analysis of Kaplan-Meier survival, univariate ANOVA, chi-squared tests for categorical variables were used. Analysis of variance (ANOVA) was used to determining the significance of impact on quantitative variables, while for qualitative variables chi-squared tests were used to compare patient from different BMI groups. ResultsThe study included 237 patients with mCRC. The median age of the patients was 65 years (range 34–82). The study group included 54% of males. The median OS and PFS in the study group was 14.6 and 8.8 months, respectively. The comparison of obese vs overweight vs normal BMI range patients revealed a significant difference in mOS (17.5 vs 14.3 vs 13.1 months, p=0.01) and mPFS (9.4 vs 9.1 vs 7.3 months, p=0.03). The regression analysis (Pearson’s linear correlation) also confirmed that there is a statistically significant relationship between the length of OS and PFS and the BMI value. Higher BMI was associated with a better prognosis. The location of the primary lesion on the left side of the colon, less than two metastatic sites and CEA within the normal range before start of the treatment was linked with statistically longer OS. ConclusionsObese and overweight patients presented longer OS and PFS compared with normal weight patients with mCRC cancer treated with bevacizumab plus FOLFOX chemotherapy regimen. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Patterns of re-irradiation for recurrent gliomas and validation of a prognostic score

Purpose or objectiveRe-irradiation is a generally accepted method for salvage treatment in patients with recurrent glioma. However, no standard radiation regimen has been defined. This study aims to compare the efficacy and safety of different treatment regimens and to independently externally validate a recently published reirradiation risk score. Material and methodsWe retrospectively analyzed a cohort of patients with recurrent malignant glioma treated with salvage conventionally fractionated (CFRT), hypofractionated (HFRT) or stereotactic radiotherapy (SRT) between 2007 and 2017 at the University Medical Centers in Utrecht and Groningen. ResultsOf the 121 patients included, 60 patients (50%) underwent CFRT, 22 (18%) HFRT and 39 (32%) SRT. The primary tumor was grade II-III in 52 patients and grade IV in 69 patients with median Overall Survival (mOS) since first surgery of 113 [Interquartile range: 53.2–137] and 39.7 [24.6–64.9] months respectively (p < 0.01). Overall, mOS from the first day of re-irradiation was 9.7 months [6.5–14.6]. No significant difference in mOS was found between the treatment groups. In multivariate analysis, the Karnofsky performance scale ≥70% (p < 0.01), re-irradiation for first recurrence (p = 0.02), longer time interval between RT start dates (p < 0.01) and smaller planning target volume (p < 0.05) were significant favorable prognostic factors. The reirradiation risk score was validated. ConclusionIn our series, mOS after reirradiation was sufficient to justify use of this modality. Until a reliable treatment decision tool is developed based on larger retrospective research, the decision for re-irradiation schedule should remain personalized and based on a multidisciplinary evaluation of each patient.

Prognostic factors in patients with loco-regionally advanced gastric cancer

BackgroundThe aim of this study was to investigate epidemiologic and prognostic factors relevant to the treatment of loco-regionally advanced gastric cancer (GC).MethodsTwo hundred and fifty-five patients with GC were identified in Uppsala County between 2000 and 2009. Patient records were analyzed for loco-regionally advanced GC defined as tumor with peritoneal involvement, excluding serosal invasion from the primary tumor only, at primary diagnosis or during follow-up. The presence or not of distant metastasis (DM), including hematogenous metastases (e.g., liver, lung, and bone) and/or distant lymph node metastases, was also analyzed. The Cox proportional hazard model was used for multivariate analysis of factors influencing survival.ResultsOne hundred and twenty patients (47% of all patients with GC; median age 70.5 years) had loco-regionally advanced disease, corresponding to an incidence of 3.8 per 100,000 person-years. Forty-one percent of these also had DM. Median overall survival (mOS) from the time of the diagnosis of loco-regionally advanced disease was 4.8 months for the total patient cohort, 5.1 months for the subgroup of patients without DM, and 4.7 months for the subgroup with DM. There was no significant difference in mOS between the subgroups with synchronous versus metachronous loco-regionally advanced GC: 4.8 months (range 0.0–67.4) versus 4.7 months (range 0.0–28.3). Using multivariate Cox analysis, positive prognostic factors for survival were good performance status at diagnosis and treatment with palliative chemotherapy and/or radiotherapy. Synchronous DM was a negative prognostic factor. The mOS did not differ when comparing the time period 2000–2004 (5.1 months, range 0–67.4) with the period 2005–2009 (4.0 months, range 0.0–28.3).ConclusionPeritoneal involvement occurred in almost half of the patients with GC in this study and was associated with short life expectancy. New treatment strategies are warranted.

1252P - Addressing disease progression in EGFRmut+ NSCLC patients

Although EGFR-Tyrosine Kinase Inhibitors (TKIs) have improved disease management in EGFR mutation-positive NSCLC patients, all patients experience disease progression (PD) and ultimately die. In current practice, EGFR-TKIs are often continued beyond PD (RECIST1.1), however optimal management at PD remains ambiguous. We set out to study the survival differences and patient characteristics associated with continuation vs discontinuation of EGFR-TKI at PD retrospectively at a single institution: the Tom Baker Cancer Centre, AB Canada (2010-2014). EGFRmut+ NSCLC patients treated with an EGFR-TKI were retrospectively analyzed. Demographic and clinical data, EGFR mutation type, treatment-variations at PD (chemotherapy, radiation, continuation with EGFR-TKI) were collected. SPSS-v19 was used to generate Kaplan-Meier survival curves. Progression-free survival (PFS) (time from initiating EGFR-TKI to PD) and time-to-complete EGFR-TKI-cessation (time from initiating EGFR-TKI to cessation of TKI completely, if extended beyond PD), were assessed. 127 EGFRmut+ NSCLC patients received EGFR-TKIs. 106/127 (83%) developed PD (RECIST 1.1) (64.8% F/35.2% M; 95% adenocarcinoma; smoking history: 47%; ex 19 del/L858R/other: 45.7%/ 35.4%/ 18.9 %). Median PFS was 7.9 months, while median overall survival (mOS) was 17.3 months. A log-rank test showed a statistical significant difference in mOS between exon 19 deletion and L858R (22.6months vs 15.0months; 95% CI, 14.8m to 21.9m; P-value = 0.014). At PD, 54.7% continued EGFR-TKI treatment; 45.2% received other forms of treatments. Female gender, PD with solitary-lesions and younger age are associated with EGFR-TKI continuation at PD. This study confirms the difference in survival of exon 19 del vs L858R patients when treated with an EGFR-TKI. Additionally, it is common practice for oncologists to continue TKI treatment beyond PD. Further analysis, by time-to-complete EGFR-TKI cessation, will provide a more stratified base for future clinical-trials exploring treatment at EGFR-TKI-PD.

Durability of responses in patients with metastatic renal cell carcinoma treated with high-dose interleukin-2 (HD IL-2).

511 Background: HD IL-2 is FDA approved for advanced renal cell carcinoma (mRCC), however, the data supporting its use is 23 years old. In 2011, a HD IL-2 patient database was established called PROCLAIMSM, and comprises the largest active prospective collection of data from mRCC and metastatic melanoma (MM) patients receiving HD IL-2 treatment and provides longitudinal real-time insights into the clinical impact of sequencing drug treatments. These data report on the outcomes and interactions with prior targeted therapies in mRCC patients in the current era. Methods: Inclusion criteria require patients to receive at least one dose of HD IL-2. Patients who received HD IL-2 and had already undergone a post-treatment scan were not eligible. Survival analysis was performed by the method of Kaplan and Meier using datasets as of July 27, 2015. Results: The overall response rate (ORR) and median overall survival (mOS) are described in Table 1. The mOS was not reached (NR) for 364 patients. The 1, 2 and 3 year survival rates were 79%, 63%, and 51%, respectively. For patients with stable disease (SD), the mOS was not reached and the 1, 2 and 3 year survival rates were 96%, 80%, and 60% respectively. There was a significant difference in mOS between SD and progressive disease (PD) patients, NR vs 15.5 months, P&lt;.0001. The mOS was not reached for patients regardless of whether or not they received targeted therapy (TT) prior to HD IL-2. There were 4 reported treatment-related deaths in 364 patients (1.1%), none of these patients had prior TT. Conclusions: PROCLAIM data demonstrate that SD, previously grouped with the non-responders, is associated with extended survival rates. HD IL-2 is an active 2ndline treatment option for patients who have failed TT. These data support that HD IL-2 has a favorable safety profile and remains an effective therapy for eligible patients with mRCC. Clinical trial information: NCT01415167. [Table: see text]

Clinical Outcome of Patients Diagnosed with Myelodysplastic Syndrome-Unclassifiable (MDS-U): Single Center Experience

Background:The 2008 World Health Organization (WHO) developed a new classification system for Myelodysplastic Syndrome (MDS). The well-defined categories are refractory anaemia with excess blasts (type 1 or 2 based on the marrow blast count being below or above 10%), refractory anaemia with or without ringed sideroblasts, refractory cytopenias with multilineage dysplasia and myelodysplastic syndromes with isolated deleted 5q. MDS cases that do not meet the diagnostic criteria of the above categories are classified myelodysplastic syndrome (MDS-U). However, few reports in the literature exist in terms of natural progression and clinical outcome of patients with MDS-U.Aim: To study the clinical outcome of patients with MDS-U.Method: A retrospective, IRB-approved, single-institution study through chart review of cases with MDS at Mayo Clinic Rochester between 1993 and 2014 was performed. Patients diagnosed with MDS based on WHO classification were included. MDS classification was based on routine Mayo Clinic pathology reports. Central independent hematopathology review for bone marrow biopsy was performed for cases diagnosed with MDS-U or simply generic MDS. Comparison between groups’ medians was done using Wilcoxon test, while survival estimates were calculated using Kaplan-Meier curves using JMP V10.Result: A total of 802 patients, who met WHO criteria for MDS, were studied. Median age was 71 years (range, 18-99), 69% were males. Median white blood cell (WBC) 3.6 x109, hemoglobin (Hbg) 9.6 g/dl, platelets (PLT) 105 x109, peripheral blood (PB) blasts 0% and bone marrow (BM) blasts 2%. Median overall survival (OS) was 28 months. One hundred nine (14%) cases transformed to AML. Out of the 802 patients, 90 (11%) patients were initially classified as MDS-U according to 2008 WHO criteria, 69% were males with median age 71 years. Upon pathology review, only 42/90 cases (47%) were confirmed to be MDS-U (group 1). Among 47 cases not meeting MDS-U, 40% were best classified as RARS, 17% refractory anemia, and 9% as 5Q del Syndrome, while 2 cases did not have any myeloid neoplasm.Group 1 had median WBC 3 x109, Hbg 9.9g/dL, PLT 71 x109, PB blasts 0% and BM blasts 0%. IPSS grouping was low, intermediate-1, intermediate-2 and high in 27%, 52%, 21% and 0%, respectively. R-IPSS grouping was very low, low, intermediate, high and very high in 15%, 42%, 15%, 21% and 6%, respectively. Median OS in group 1 was 68, 37, 13 and 0 months per IPSS (p=0.04), and 101, 44, 14, 11, 13 months per IPSS-R (p=0.005), respectively. Of the 43 patients with MDS-U, 39 had follow-up; 21 patients (54%) of which progressed. MDS-U became 42% RAEB, 24% RCMD, 14% CMML, 5% RARS, 10% MDS/MPN, and 5% atypical. Group 2 (MDS other than MDS-U) 759 patients had median age 71 years, 69% were males. They had WBC 3.6 x109, Hbg 9.6g/dL, PLT 107 x109(p=0.01), PB blasts 0% and BM blasts 0%. IPSS grouping was low, intermediate-1, intermediate-2 and high in 29%, 44%, 22% and 5% respectively. R-IPSS grouping was very low, low, intermediate, high and very high in 17%, 32%, 20%, 17% and 14% respectively. On comparison between Group 1 vs 2, mOS was 27 vs 29 months (p=0.7), and percentage transformed to AML 14% in both groups. On multivariate analysis for mOS only age, IPSS-R and IPSS but not MDS-U nor gender were statistically significant.Conclusion: MDS-Uis a small subset of MDS. With independent pathology review, half of the MDS-U cases were subclassified into other MDS groups. In follow-up more than half of the cases were subclassified into other MDS groups and some were non-MDS. IPSS and IPSS-R are helpful tools for survival assessment in MDS-U. High risk MDS was infrequent in MDS-U per IPSS. We found no significant difference in mOS nor AML transformation when comparing MDS-U to other groups. DisclosuresNo relevant conflicts of interest to declare.

791P - Sequencing of Docetaxel (D) and Abiraterone Acetate (Aa) for Metastatic Castration-Resistant Prostate Cancer (Mcrpc)

ABSTRACT Aim: D and AA are approved as front-line treatments for mCRPC. Their optimal sequencing is as yet undefined. We retrospectively evaluated whether sequencing of AA and D has an effect on survival in mCRPC. Methods: We retrospectively identified mCRPC patients (pts) who received both D and AA at the Royal Marsden Hospital. Pts were divided into two groups, the first having received D followed by AA (D- > AA) and the second AA followed by D(AA- > D). Pts who received D in the non-castrate setting or enzalutamide prior to D or AA were excluded. Hormonal treatments or phase I/II investigational agents were allowed between D and AA. Cabazitaxel(C) was allowed either before or after the second part of treatment. Overall survival (OS) was defined as time from initiation of first treatment, D or AA, to death or last follow-up (LFU). Log-Rank testing was used to compare OS between the two groups and two-sided Pearson's Chi-Square and Student's t-test to compare categorical and continuous variables respectively. Results: Time between treatment stages in months. Mean; Median (Min;Max) Diagnosis to CRes CRes to D End of D to AA End of AA to C End of AA to LFU D- > AA 50.0;33.8 (2.4;190.1) 15.0;10.3 (0.0;122.1) 11.5;9.2 (0.0;47.8) -1.5;1.0 (-17.0;9.1) 9.7;6.8 (0.0;57.0) Diagnosis to CRes Cres to AA End of AA to D End of D to C End of D to LFU AA- > D 54.4;35.8 (4.8;210.7) 14.9;13.7 (0.2;71.5) 7.5; 4.0 (0.9; 28.5) 14.7;9.2 (1.6;38.8) 12.5;8.2 (0.4;51.0) CRes: Castration Resistance. Between 10/2004 and 06/2012 161 and 37 mCRPC pts were identified who received D- > AA and AA- > D respectively. Baseline mean values of prognostic parameters were comparable in the two groups: Hg was 11.9g/dl and 12.7g/dl (p = 0.04), LDH 195.2u/l and 203.6u/l(p = 0.5), ALP 252.1u/l and 156u/l(p = 0.1), albumin 35.2g/l and 36.9g/l(p = 0.06), PSA 786.3ng/ml and 118.7ng/ml (p = 0.7) –median(m)PSA 131ng/ml and 72ng/ml- in D- > AA and AA- > D group respectively. Similar proportion of pts received C in the two groups: 36 pts (22.4%) in D- > AA and 4 (10.8%) in AA- > D (p = 0.1). After a mFU of 2.7 years 18 pts (11.2%) in the D- > AA group were alive and 2 (5.4%) in the AA- > D group; mOS was 31.4 months (95%CI: 28.3-34.4) in D- > AA and 38.6months (95% CI:30.3-46.9) in AA- > D (p = 0.6). The difference was not statistically significant. Conclusions: This retrospective analysis did not identify a statistically significant difference in mOS between pts treated with D- > AA or AA- > D. Prospective studies to evaluate optimal treatment sequencing for mCRPC are warranted. Disclosure: Z. Zafeiriou: Employee at the time of manuscript preparation of the Institute of Cancer Research, Sutton, Surrey, UK, that has commercial interest in abiraterone. Z.Z has received grants from Hellenic Society of Medical Oncology; R. Ferraldeschi, A. Altavilla, S. Sideris, P. Rescigno, D. Bianchini, A. Smith, R. Perez Lopez, N. Mehra, P. Ravi, E. Grist and N. Tunariu: Employee at the time of manuscript preparation of the Institute of Cancer research, Sutton, Surrey, UK, that has commercial interest in abiraterone; A. Omlin: Employee at the time of manuscript preparation of the Institute of Cancer research, Sutton, Surrey, UK, that has commercial interest in abiraterone. Advisory role: Janssen as COI; C. Pezaro and D. Mukherji: Employee at the time of manuscript preparation of the Institute of Cancer research, Sutton, Surrey, UK, that has commercial interest in abiraterone. Has has received honoraria from Sanofi-Aventis and Janssen-Cilag; D. Lorente: Employed at the Institute of Cancer Research, which has a commercial interest in the development of abiraterone; J. Mateo: Employed at the Institute of Cancer Research when the abstract was created, which has a commercial interest in the development of this agent; G. Attard: GA is listed in the ICR co-inventors reward scheme for abiraterone acetate; J.S. de Bono: JSB has a consultant role with Johnson & Johnson, and received honoraria from Johnson & Johnson. Consultant and Chief Investigator of the Abiraterone Trial.

A model to predict the feasibility of concurrent chemoradiotherapy with temozolomide in glioblastoma multiforme patients over age 65.

2040 Background: It is controversial whether concurrent chemoradiotherapy (CRT) with temozolomide is feasible and beneficial in elderly patients with glioblastoma (GBM). Methods: Retrospective analysis of 76 elderly GBM patients (≥ 65 years) treated with concurrent CRT with temozolomide. Factors influencing prognosis and feasibility of CRT were investigated. Results: Median overall survival (mOS) was 11.3 months. Univariate analysis showed a significant difference in mOS for cumulative dose of concurrent temozolomide (optimal cutoff, 2655 mg/m²; 13.9 months for > 2655 mg/m² v 4.9 months for ≤ 2655 mg/m²; P = .0103). Significant independent prognostic parameters in multivariate analysis were: a cumulative dose of concurrent temozolomide > 2655 mg/m² (hazard ratio [HR], 0.41; P = .008), thrombocytopenia grade III/IV (HR, 3.05; P = .034), and biopsy only (HR, 2.10; P = .022). Hematotoxicity was the most common cause of treatment interruption or discontinuation in patients with an insufficient cumulative temo...

A Retrospective Study of Palliative Cisplatin-Based Doublet Chemotherapy for Malignant Pleural Mesothelioma

Objectives: Cisplatin-based doublet-chemotherapy is the standard palliative treatment for malignant pleural mesothelioma (MPM) supplemented with palliative radiotherapy when indicated by symptoms. This work aims to study the epidemiologic characteristics and overall survival rates of patients with MPM treated with palliative chemotherapy in one institution year 2000 - 2010. Materials and Methods: Review of journals. Data were structured using the Aarhus Lung Cancer Register and statistics were analyzed using SPSS software. Results: The median age of the 80 patients (70 males and 10 females) at diagnosis was 63 years (range 40-80). 46% of the patients had epithelioid histological subtype. As first line treatment 21 patients received cisplatin/vinorelbine iv., 29 patients received cisplatin/pemetrexed and 11 patients received pemetrexed as monotherapy. Median overall survival (mOS) for the whole group was 13.1 months (95% CI 10.1-16.2). We found no significant difference in mOS between patients treated with cisplatin/vinorelbine (mOS 17.0 months, 95% CI 12.6-21.4) and cisplatin/pemetrexed (mOS 14.0 months, 95% CI 8.9-19.1), p=0.598. Patients with epithelioid subtype had a significantly better mOS (15.2 months, 95% CI 11.6-18.8) compared to patients with non-epithelioid subtype (8.9 months, 95% CI 5.6-12.2), p=0.026. Conclusion: Subtype of histology is significantly associated with survival in MPM. Patients with epithelioid histology have a better prognosis than patients with non-epithelioid subtype. Our results show no significant difference in overall survival in patients who received different cisplatin-based doublet-regimes. The survival rates in this retrospective study are comparable to other published data. Randomized trials exploring cisplatin-based doublet regimens like cisplatin/pemetrexed and cisplatin/vinorelbine po. are needed.

Analysis of long-term survival in patients with glioblastoma.

e13007 Background: Adult glioblastoma (GBM) is the most common type of malignant primary brain tumor. Despite advances made in treatment, median survival is between 12 and 15 months. Standard care is concomitant radiotherapy (RT)/temozolomide (TMZ) and adjuvant TMZ for 6 cycles (EORTC/NCIC trial 2005). At progression, subsequent treatments are left to the discretion of the treating physician. Methods: We evaluated retrospective data of GBM patients (pts) treated from 2003 to 2010, focusing on the treatment of patients with longer survival (over 24 months). Results: 139 pts with GBM were treated during the period. Thirty of these showed survival &gt; 24 months: 20 were subjected to macroscopically radical neurosurgery, 9 to non-radical surgery and 1 to biopsy. All pts had a KPS 100%. 11 pts were treated in the period pre-EORTC/NCIC trial (Stupp et all) and 19 in the period “post-Stupp”. In the former group 10 pts underwent RT followed by TMZ ( 2-12cycles) and 1 patient received only RT. All pts in the latter group were treated with concomitant radio-chemotherapy followed by TMZ. 3 pts are currently disease stable. After the first documented evidence of disease progression (PD) 21 pts were treated, one with neurosurgery, 4 with neurosurgery plus chemotherapy (CT), 15 with only CT and 1 with CT and tomotherapy. With regard to chemotherapy, 14 pts received TMZ ( 2-21cycles), 3 fotemustine (4-16 cycles), 1 carboplatin and VP16 (2 cycles) and 1 irinotecan plus bevacizumab (2 cycles). Further progression was treated with another line of CT in only 8 pts, fotemustine in 5 (1-3 cycles), TMZ in 2 (2 cycles) and carboplatin plus VP16 In 1 (5 cycles). Median overall survival (mOS) of our long-term survivors was 36.18 months (CI 95% 28.32 – 42.01). Considering the two groups separately (pre- and post- Stupp), we observed a mOS of 36.18 months (CI 95% 26.45 – 42.01) (1 pt alive) for the first group and of 36.15 months (CI 95% 28.26 – 48.52) (7 pts alive) for the second. Conclusions: Our long-term survivors, independently of treatment, showed an mOS of 36.18 months (CI 95% 28.32 – 42.01). There was no significant difference in mOS between the 2 groups (p=0.6963). Further research is needed to identify the biomolecular and genetic pattern that is responsible for the long survival of some patients.