5-year Event-free Survival Rates Research Articles

Impacts of radiation dose on survival in 72 patients with average-risk medulloblastoma

Objective To retrospectively analyze the impacts of a craniospinal radiation dose ≤24 Gy or>24 Gy on the prognosis of patients with average-risk medulloblastoma. Methods Average-risk medulloblastoma was defined as non-metastatic cancer in children more than 3 years old with complete or near-complete (residual tumor ≤1.5 cm3) resection of tumor. A total of 72 children and adolescents with newly diagnosed average-risk medulloblastoma were enrolled as subjects from 2003 to 2013. After radical resection of the tumor, all patients received craniospinal plus local tumor bed radiotherapy and 8 cycles of adjuvant chemotherapy using cisplatin-, semustine-, or plus vincristine-based regimens. Patients exposed to a radiation dose ≤24 Gy were enrolled into Group A (n=20), while patients exposed to a radiation dose>24 Gy were enrolled into Group B (n=52). The recurrence rate and survival rate were compared between the two groups. The recurrence rate and survival rate were calculated using the Kaplan-Meier method and the differences between the two groups were analyzed using the log-rank test. Results Patients in Group A and Group B received craniospinal radiotherapy with a dose of 19.2-24.0 Gy and 24.1-30.6 Gy, respectively. After radiotherapy, 66 patients (92%) completed all adjuvant chemotherapy. A total of 11 patients were recurrence. In all patients, the 3-year sample size was 48; the 3-year event-free survival (EFS) and overall survival (OS) rates were 83% and 86%, respectively. There were no significant differences in the 3-year EFS and OS rates between Group A and Group B (84% vs. 83%, P=0.609; 85% vs. 87%, P=0.963). Conclusions The standard comprehensive therapy achieves satisfactory treatment outcomes for average-risk medulloblastoma, in which a craniospinal radiation dose decreased to 19.2-24.0 Gy has no impacts on treatment outcomes. Key words: Medulloblastoma, average-risk/radiotherapy; Medulloblastoma, average-risk/chemotherapy; Prognosis

Allergic reactions and antiasparaginase antibodies in children with high-risk acute lymphoblastic leukemia: A children's oncology group report.

The objectives of this study were to assess the incidence of clinical allergy and end-induction antiasparaginase (anti-ASNase) antibodies in children with high-risk acute lymphoblastic leukemia treated with pegylated (PEG) Escherichia coli ASNase and to determine whether they carry any prognostic significance. Of 2057 eligible patients, 1155 were allocated to augmented arms in which PEG ASNase replaced native ASNase postinduction. Erwinia chrysanthemi (Erwinia) ASNase could be used to replace native ASNase after allergy, if available. Allergy and survival data were complete for 990 patients. End-induction antibody titers were available for 600 patients. During the consolidation phase, 289 of 990 patients (29.2%) had an allergic reaction. There were fewer allergic reactions to Erwinia ASNase than to native ASNase (odds ratio, 4.33; P < .0001) or PEG ASNase (odds ratio, 3.08; P < .0001) only during phase 1 of interim maintenance. There was no significant difference in 5-year event-free survival (EFS) between patients who received PEG ASNase throughout the entire study postinduction versus those who developed an allergic reaction to PEG ASNase during consolidation phase and subsequently received Erwinia ASNase (80.8% ± 2.8% and 81.6% ± 3.8%, respectively; P = .66). Patients who had positive antibody titers postinduction were more likely to have an allergic reaction to PEG ASNase (odds ratio, 2.4; P < .001). The 5-year EFS rate between patients who had negative versus positive antibody titers (80% ± 2.6% and 77.7% ± 4.3%, respectively; P = .68) and between patients who did not receive any ASNase postconsolidation and those who received PEG ASNase throughout the study (P = .22) were significantly different. The current results demonstrate differences in the incidence rates of toxicity between ASNase preparations but not in EFS. The presence of anti-ASNase antibodies did not affect EFS.

Treatment of children with highly suspected mature B-cell lymphoblastic leukemia

Objective To evaluate the outcomes of mature B-cell acute lymphoblastic leukemia(mature B-ALL)and to assess the safety and efficacy of the treatment protocol. Methods From February of 2003 to December of 2012, 15 children were diagnosed as mature B-cell acute lymphoblastic leukemia/lymphoma possible (mature B-ALL/NHLp) in Shanghai Children's Medical Center(SCMC) were enrolled, and they were treated with SCMC-mature B-ALL/NHLp-2003 protocol .All of the clinical characteristics, therapeutic effects and long-term outcomes were analyzed.The statistical data were processed by SPSS 21.0. Results The median age on diagnosis was 8.7 years (1 year and 5 months to 14 years and 4 months). Among them, 4 cases presented with local mass including maxillofacial tumors, neck and abdominal mass.The others had systemic manifestations such as fever and pale face. These neoplastic cells retained the expressions of surface membrane immunoglobulin M, terminal deoxynucleotidyl transferase, Cμ, CD10, CD19, cCD79a differently.Follow-up was updated to November 30, 2013.The median follow-up period was 80 months(39-128 months). Theestimated 5-year event free survival rate was (80.0±10.3)%.According to univariate analysis, increased lactate dehydrogenase level (> 4-times the normal value), increased serum ferritin level (> 2-times the normal value), no small residual disease markers were indepen-dent poor prognostic factors(χ2=5.49, 4.89, 5.49, all P<0.05). Conclusions SCMC-mature B-NHL/ALLp-2003 protocol is feasible and safe for children with mature B-ALL/NHLp, but more sample cases need to be investigated. Key words: Mature B-cell acute lymphoblastic leukemia/lymphoma; Child; Curative effect; Event-free survival

Abstract 2197: Effect of tolfenamic acid on the therapeutic efficacy of chemotherapeutic drugs used in the treatment of Ewing sarcoma

Abstract Ewing sarcoma (ES) is the second most common pediatric primary bone tumor, and affects children between the ages of 1 to 20 years. With the advancement in therapeutic options the 5-year event free survival rate of patients with localized tumor has gone up to 70%. However, in patients with metastases at diagnosis, this rate is less than 20%. One of the distinguishing hallmarks of ES is the presence of oncogenic fusion transcription factor formed by the translocation between EWS and ETS family transcription factor. The EWS-FLI1 translocation is most commonly found in ES patients. Therefore targeting EWS-FLI1 transcription factor or its downstream targets presents a novel therapeutic approach to treat ES. Research from our group demonstrated the anti-cancer activity of a small molecule, Tolfenamic acid (TA) in pediatric cancers, leukemia, neuroblastoma and medulloblastoma. TA has been shown to target transcription factor Sp1, which regulates the expression of several genes associated with cancer including survivin, a member of inhibitor of apoptosis protein (IAP) family and involved in chemoresistance. It is currently in phase I clinical trials for treating upper gastro-intestinal cancer patients along with radiation. In this study, we evaluated the therapeutic efficacy of TA alone and in combination with chemotherapeutic drugs, and its effect on the EWS-FLI1 downstream targets. ES cell lines CHLA9, CHLA10 and TC71 were treated with TA, Etoposide, Doxorubicin and Vincristine and cell viability was measured at 24 and 48h post-treatment. TA and chemotherapeutic drugs caused a dose and time dependent inhibition of cell proliferation. We then assessed the effects of TA in combination with these chemotherapeutic drugs. Results indicate that the combination treatment causes increased (2-3 fold) inhibition of cell viability compared to individual agents. To access the mode of action of combination therapy, cells were treated with TA and Vincristine and apoptosis was monitored at 48h post-treatment via western blot analysis (c-PARP), flow cytometry (Annexin V staining), and caspase 3/7 activity (Caspase3/7-Glo assay). We were able to demonstrate that the inhibition of cell viability in the combination treatment was the result of apoptotic mechanism as determined by increased cleavage of PARP and up-regulation of caspase 3/7activity. In addition we also studied the effects of TA on the regulation of EWS-FLI1 downstream targets NROB1, ID2, ROCO1 and LDB2 by real-time PCR. Results demonstrate that TA treatment leads to the downregulation of EWS-FLI1 genes. Taken together our results indicate that the combination of TA and chemotherapy drugs inhibits the proliferation of sarcoma cells. This investigation also suggests that the proposed combination therapy involving small molecule TA and standard chemotherapeutic agents could be a viable strategy for the treatment of Ewing sarcoma. Citation Format: Umesh T. Sankpal, Anish Ray, Leslie Tabor-Simecka, W Paul Bowman, Riyaz M. Basha. Effect of tolfenamic acid on the therapeutic efficacy of chemotherapeutic drugs used in the treatment of Ewing sarcoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2197. doi:10.1158/1538-7445.AM2015-2197

Intensified chemotherapy without SCT in infant ALL: results from COG P9407 (Cohort 3).

Infants with acute lymphoblastic leukemia (ALL) present with aggressive disease and a poor prognosis. Early relapse within 6-9 months of diagnosis is common. Approximately 75% of infants have MLL-rearranged (MLL-R) ALL with event free survival (EFS) ranging from 20% to 30%. Children's Oncology Group (COG) P9407 used shortened (46 weeks), intensified therapy to address early relapse and poor EFS. P9407 therapy was modified three times for induction toxicity resulting in three cohorts of therapy. One hundred forty-seven infants were enrolled in the third cohort. We report an overall 5-year EFS and OS of 42.3 ± 6% and 52.9 ± 6.5% respectively. Poor prognostic factors included age ≤90 days at diagnosis, MLL-R ALL and white cell count ≥50,000/μl. For infants ≤90 days of age, the 5-year EFS was 15.5 ± 10.1% and 48.5 ± 6.7% for those >90 days (P < 0.0001). Among infants >90 days of age, 5-year EFS rates were 43.8 ± 8% for MLL-R versus 69.1 ± 13.6% for MLL-germline ALL (P < 0.0001). Age ≤90 days at diagnosis was the most important prognostic factor. Despite shortened therapy with early intensification, EFS remained less than 50% overall in MLL-R ALL.

Adult Ewing Sarcoma

To assess the clinical features and outcomes in adult patients with metastatic Ewing sarcoma (ES). The records of 36 ES patients with metastatic disease ≥ 18 years seen from 1977 to 2007 at the Mayo Clinic were studied retrospectively. Factors relevant to prognosis, survival, and local control (LC) were analyzed. The 4-year overall survival (OS) and event-free survival (EFS) rates were 20% and 11%, respectively. Patients treated from 1993 to 2007 had significantly improved outcomes compared with those treated from 1977 to 1992: 4-year OS and EFS of 31% and 16%, respectively, versus 0% (P = 0.01). Primary tumor (P = 0.005 and 0.04) and metastatic sites (P = 0.05) were independent EFS prognostic factors. Four patients (11%) received surgery, 18 (50%) radiation therapy (RT), 4 (11%) surgery + radiation therapy (S+RT), and 10 (28%) received no LC. The 4-year EFS rates were 0% for surgery, 21% for RT, 0% for S + RT, and 0% for no LC (P = 0.0001). OS in patients who received vincristine, doxorubicin, and cyclophosphamide alternating with ifosphamide and etoposide (VDC/IE) chemotherapy was improved (P = 0.04). Relapses were documented in 18 patients (excluding patients who received no LC). In total, 44% of patients had all of their metastatic site(s) treated. Patients who received treatment to all extrapulmonary metastases had significantly improved outcomes compared with those who did not receive treatment to all sites: 4-year OS and EFS of 33% and 11%, respectively, versus 0% (P = 0.04 and 0.02). Our results suggest outcomes for adult patients with metastatic ES are similar to pediatric cohorts in the modern era. VDC/IE chemotherapy and treatment to all metastatic lesions is associated with improved outcomes.

Prognostic significance of histological invasion in high grade soft tissue sarcomas.

High grade soft tissue sarcomas often show histological invasion to adjacent compartment including bone and vessel. This study aimed to evaluate histological invasion in high grade soft tissue sarcomas, clarify its impact on prognosis and devise treatment strategies. We retrospectively reviewed 133 patients with non-small round cell high grade soft tissue sarcomas surgically treated between 2001 and 2011. Clinical and histological factors examined for prognostic value included age, gender, size, depth, location, adjuvant therapy and invasion to adjacent compartment. Study endpoints included overall survival rate, event free survival rate and local recurrence free survival rate, estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed using the log-rank test and Cox proportional hazards model. Local recurrence was recognized in 14 cases (11%). The 5-year overall survival rate and 5-year event free survival rate were 82.2% and 63.6% respectively. The metastasis-free survival rate at 5 years and local recurrence-free survival rate at 5 years were 69.8% and 86.8% respectively. Histological invasion to adjacent compartment was noted in 52 cases (39%), and was significantly correlated with histological type (p = 0.01), tumor size (p = 0.009), and depth (p < 0.05). In multivariate analyses, we showed that tumor size and histological invasion were significant independent predictors of OS (hazard ratio 8.1/2.5) and EFS (hazard ratio 5.5/2.2), while only tumor size was a significant independent predictor of LRFS (hazard ratio 4.0). We evaluated the relation between histological invasion and the oncological outcomes of high grade soft tissue sarcomas. In multivariate analyses, histological invasion was found to be an independent adverse prognostic factor with hazard ratios of 2.2-2.5, suggesting that a detailed assessment of these factors is essential. Histological invasion showed a correlation with tumor size and histological type, and the surgical margin should be decided based on these factors.

Clinical features of coronary artery ectasia in the elderly.

ObjectiveTo investigate the incidence, imaging and clinical characteristics in elderly patients with coronary artery ectasia (CAE).MethodsA retrospective analysis was conducted on patients with CAE who underwent coronary angiography between January 2006 and December 2012. According to age, the enrolled patients were divided into two groups (elderly group, age ≥ 65 years; non-elderly group, age < 65 years). The clinical feature, imaging characteristics and the 5-year survival rate of the two groups were compared.ResultsThe prevalence of CAE in elderly patients was 0.33%. Patients in elderly group were found to have significantly higher proportion of female (30.1% vs. 10.1%, P < 0.001), three-vessel disease (60.5% vs. 45.2%, P = 0.003) and localized ectasia (55.0% vs. 40.2%, P = 0.003). In addition, body mass index (20.90 ± 2.71 kg/m2 vs. 22.31 ± 2.98 kg/m2, P < 0.001) and percentage of current smokers (45.0% vs. 64.6%, P < 0.001) were significantly lower in elderly group. Cumulative survival curves demonstrated reduced 5-year cumulative survival at the follow-up in the elderly group compared with the non-elderly group (88.0% vs. 96.0%, P = 0.002). But the 5-year event free survival rate failed to show a significant difference between the two groups (31.0% vs. 35.0%, P = 0.311).ConclusionThe prevalence of CAE in elderly patients was 0.33%, which was about 1/3 of the entire numbers of CAE patients. There were significant differences between the elderly and the non-elderly patients with CAE in terms of coronary artery disease risk factors and coronary artery ectatic characteristics. CAE might be associated with increased mortality risk in the elderly.

The clinical characteristics and treatment outcome of 57 children and adolescents with primary central nervous system germ cell tumors.

Primary central nervous system germ cell tumors (CNS-GCTs) in children and adolescents have unique clinical features and methods of treatment compared with those in adults. There is little information about Chinese children and adolescents with CNS-GCTs. Therefore, in this study we retrospectively analyzed the clinical features and treatment outcome of Chinese children and adolescents with primary CNS-GCTs. Between January 2002 and December 2012, 57 untreated patients from a single institution were enrolled. They were diagnosed with CNS-GCTs after pathologic or clinical assessment. Of the 57 patients, 41 were males and 16 were females, with a median age of 12.8 years (range, 2.7 to 18.0 years) at diagnosis; 43 (75.4%) had non-germinomatous germ cell tumors (NGGCTs) and 14 (24.6%) had germinomas; 44 (77.2%) had localized disease and 13 (22.8%) had extensive lesions. Fifty-three patients completed the prescribed treatment, of which 18 underwent monotherapy of surgery, radiotherapy, or chemotherapy, and 35 underwent multimodality therapies that included radiotherapy combined with chemotherapy or surgery combined with chemotherapy and/or radiotherapy. PEB (cisplatin, etoposide, and bleomycin) protocol was the major chemotherapy regimen. The median follow-up time was 32.3 months (range, 1.2 to 139 months). Fourteen patients died of relapse or disease progression. The 3-year event-free survival (EFS) and overall survival rates for all patients were 72.2% and 73.8%, respectively. The 3-year EFS was 92.9% for germinomas and 64.8% for NGGCTs (P = 0.064). The 3-year EFS rates for patients with NGGCTs who underwent monotherapy and multimodality therapies were 50.6% and 73.5%, respectively (P = 0.042). Our results indicate that multimodality therapies including chemotherapy plus radiotherapy were better treatment option for children and adolescents with CNS-GCTs.

Double hit lymphoma: the MD Anderson Cancer Center clinical experience.

We report our experience with 129 cases of double hit lymphoma (DHL), defined as B-cell lymphoma with translocations and/or extra signals involving MYC plus BCL2 and/or BCL6. All cases were reviewed for histopathological classification. Median age was 62years (range, 18-85), 84% of patients had advanced-stage disease, and 87% had an International Prognostic Index score ≥2. Fourteen patients (11%) had a history of low-grade follicular lymphoma. MYC translocation was present in 81%, and extra signals of MYC in 25% of patients. IGH-BCL2 translocation was present in 84% and extra signals of BCL2 in 12% of patients. Two-year event-free survival (EFS) rates in all patients and patients who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), and R-HyperCVAD/MA (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, alternating with cytarabine plus methotrexate) were 33%, 25%, 67% and 32%, respectively. In patients achieving complete response with initial therapy (n=71), 2-year EFS rates in patients who did (n=23) or did not (n=48) receive frontline stem cell transplantation were 68% and 53%, respectively (P=0·155). The cumulative incidence of central nervous system involvement was 13% at 3years. Multivariate analysis identified performance status ≥2 and bone marrow involvement as independent adverse prognostic factors for EFS and OS. Further research is needed to identify predictive and/or targetable biological markers and novel therapeutic approaches for DHL patients.

Involved-Node Proton Therapy in Combined Modality Therapy for Hodgkin Lymphoma: Results of a Phase 2 Study

This study describes the early clinical outcomes of a prospective phase 2 study of consolidative involved-node proton therapy (INPT) as a component of combined-mode therapy in patients with stages I to III Hodgkin lymphoma (HL) with mediastinal involvement. Between September 2009 and June 2013, 15 patients with newly diagnosed HL received INPT after completing chemotherapy in an institutional review board-approved protocol comparing the dosimetric impact of PT with those of three-dimensional conformal radiation therapy (3DCRT) and intensity modulated RT. Based on (18)F-Fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) response, 5 children received 15 to 25.5 cobalt Gy equivalent (CGE) of INPT after receiving 4 cycles of Adriamycin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide or Vincristine, adriamycin, methotrexate, Prednisone chemotherapy, and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles of Adriamycin, Bleomycine, Vinblastine, Dacarbazine. Patients were routinely evaluated for toxicity during and after treatment, using Common Terminology Criteria for Adverse Events, version 3.0, and for relapse by physical examination and routine imaging. Relapse-free survival (RFS) and event-free survival (EFS) rates were calculated using the Kaplan-Meier method from the time of diagnosis. The median follow-up was 37 months (range, 26-55). Two events occurred during follow-up: 1 relapse (inside and outside the targeted field) and 1 transformation into a primary mediastinal large B cell lymphoma. The 3-year RFS rate was 93%, and the 3-year EFS rate was 87%. No acute or late grade 3 nonhematologic toxicities were observed. Although decades of follow-up will be needed to realize the likely benefit of PT in reducing the risk of radiation-induced late effects, PT following chemotherapy in patients with HL is well-tolerated, and disease outcomes were similar to those of conventional photon therapy.

Clinical characteristics and prognosis of core binding factor positive acute myeloid leukemia in children

Objective To explore the clinical characteristics and prognosis of core binding factor(CBF)positive acute myeloid leukemia(AML)in children. Methods Eighty-five children with AML who were not acute promyelocytic leukemia (APL) and Downs syndrome were enrolled in this study and received more than one course of chemotherapy from Jun.2007 to Jun. 2012 in Children's Hospital of Soochow University.They were divided into low-risk group, medium-risk group, high-risk group according to national unity stratification criteria to confirm their survival condition, analyze the effection of prognosis of sex, FAB type, initial white blood cell number, CBF, chromosome, complete remission course, central nervous system leukemia(CNSL), relapse, hematopoietic stem cell transplantation(HSCT). Forty cases with CBF positive AML were evaluated with Kaplan-Meier survival curves of 5-year overall survival(OS) rate and event-free survival(EFS) rate, CBF negative AML as control group. Results Five-year OS rates of low-risk, intermediate-risk and high-risk group were (66.5±11.6)%, (54.5±14.4)% and(42.7±7.2)% respectively, there was significant difference(χ2=6.085, P=0.048); and the 5-year EFS rates were (62.2±14.0)%, (54.5±14.4)% and(41.9±7.3)% respectively, there was no significant difference(χ2=1.060, P=2.589). Cases of distribution of CBF positive AML were 22/23 cases in low-risk group, 3/11 cases in medium-risk group and 15/51 cases in high-risk group.Twenty-three cases survived in CBF positive AML group, 24 cases survived in control group, and their 5-year OS rates were(51.8 ± 8.8)%, (50.6±7.6)%, respectively.Ten cases relapsed, including 6 cases with CBF positive(3 cases death) and 4 control cases(2 cases death). Twenty cases received HSCT, including 5 cases with CBF positive (1 case death) and 15 control cases(3 cases death). COX regression multivariate analysis showed that gender, numbers of course of induction chemotherapy to remission and HSCT were individually statistic significance for pediatric AML's prognosis while the FAB classification, initial leukocyte count and central nervous system leukemia had no effect on prognosis. Conclusions There is no significantly statistic difference between CBF positive AML and its control in chemotherapy group.The survival rate in control group and all cases in pediatric AML could be obviously improved by HSCT. Key words: Core binding factor; Leukemia; Myeloid; Acute; Prognosis; Child

Abstract P5-17-01: A definition of a high-risk early-breast cancer population based on data from the collaborative trials in neoadjuvant breast cancer (CTNeoBC) meta-analysis

Abstract Background: Pathological complete response (pCR) is a proposed surrogate endpoint for predicting long-term clinical benefit on endpoints such as event-free survival (EFS) or overall survival (OS). The CTNeoBC meta-analysis did not validate the surrogacy of pCR for EFS or OS, and there is no precedent for its use as a regulatory endpoint in oncology. Use of the accelerated approval pathway has been proposed for neoadjuvant therapies that substantially improve pCR as a means to expedite widespread access to highly effective therapies for high-risk, early breast cancer. Potential risks of this approach include approving an agent that ultimately does not demonstrate clinical benefit and, in the interim, exposing curable patients to the toxicity of therapy without certainty of benefit. To mitigate the risks of this pathway, enrollment to neoadjuvant trials intended to support accelerated approval should be restricted to patients presenting with high-risk early-stage breast cancer. The 5-year EFS rate by breast cancer subtype in the CTNeoBC meta-analysis population is presented. Methods: We identified 12 neoadjuvant randomized trials (N = 12,993) with pCR clearly defined and long-term follow-up available for EFS and OS. Trials included AGO 1 (n = 668), ECTO (n = 1355), EORTC 10994/BIG 1-00 (n = 1856), GeparDuo (n = 907), GeparQuattro (n = 1495), GeparTrio (n = 2072), GeparTrio-Pilot (n = 285), NOAH (n = 234), NSABP B18 (n = 760), NSABP B27 (n = 2411), PREPARE (n = 733), and TECHNO (n = 217). The key objective of this analysis was to establish a definition of “high-risk” based on the Kaplan-Meier estimates of the 5-year EFS rate in the different clinical breast cancer subtypes (hormone receptor-positive, HER2-positive and triple-negative) analyzed by tumor stage and tumor grade at presentation. Results: The 5-year EFS rate was less than 65% in all the breast cancer subtypes with stage III disease. For patients with stage II disease, the impact of tumor grade varied by hormone receptor status. Patients with hormone receptor-negative breast cancer, regardless of HER2 status had a poor prognosis that was independent of tumor grade. For patients with hormone receptor-positive tumors, regardless of HER2 status, high grade histology was associated with an increased risk of recurrence. 5-year Event-Free Survival Rate (EFS) 5-year EFS Rate Estimate (95% confidence interval)TNMStage IIStage III Grade IIGrade IIIGrade IIGrade IIIHormone Receptor + HER2-83% (80%, 85%)71% (65%, 77%)63% (58%, 69%)51% (42%, 59%)HER2+ HR+81% (75%, 86%)69% (60%, 76%)50% (41%, 59%)48% (37%, 59%)HER2+ HR-61% (51%, 70%)66% (57%, 73%)58% (46%, 69%)46% (36%, 55%)Triple Negative66% (58%, 72%)72% (67%, 76%)38% (27%, 48%)37% (29%, 45%) Conclusions: This analysis estimated the 5-year EFS rate in the breast cancer subtypes from the CTNeoBC meta-analysis population. The HER2-positive population in the meta-analysis was at particularly high risk because most of the patients had locally advanced breast cancer and only 39% of these patients received trastuzumab therapy. We propose defining less than 75% 5-year EFS rate as “high-risk” for the purposes of designing neoadjuvant trials that intend to use pCR to support accelerated approval. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-17-01.

Predicting survival for multiple myeloma patients using baseline neutrophil/lymphocyte ratio

The neutrophil/lymphocyte ratio (NLR) at diagnosis has been shown to be a prognostic factor for survival in solid tumors. The NLR at diagnosis as a prognostic factor for multiple myeloma (MM) has not been studied. Therefore, the focus of the study was the correlation of NLR with the proven prognostic parameters in patients with MM. A total of 151 MM patients who fulfilled the International Myeloma Working Group (IMWG) criteria were enrolled in the study by a retrospective review of the patients' records. One hundred fifty-one age- and gender-matched healthy controls were also included in the study. NLR was calculated using data obtained from the complete blood count (CBC). NLR was significantly higher in MM patients than the control group (2.79 ± 1.82 vs. 1.9 ± 0.61, respectively; p < 0.0001). The median follow-up on living patients in this study was 41months. NLR at the diagnosis was found to be an independent predictor for overall survival (OS) and event-free survival (EFS) by univariate and multivariate analysis. Patients with a NLR <2 at diagnosis experienced superior OS compared with patients with a NLR ≥2 (5-year OS rates were 87.5 and 42.4%, respectively; p < 0.0001). In a similar fashion, superior EFS was observed in patients with a NLR <2 at the diagnosis compared with patients with a NLR ≥2 (5-year EFS rates were 88.4 and 41.8%, respectively, p < 0.0001). This study suggests that NLR at the diagnosis is a simple, inexpensive, possible prognostic factor to assess clinical outcomes in MM patients.

The predictive value of DE-CMR in patients with severe chronic aortic regurgitation and extremely dilated left ventricular chamber

To determine whether preoperative contrast delay-enhanced cardiovascular magnetic resonance imaging (DE-CMR) could help predict long-term survival of patients with severe chronic aortic regurgitation and extremely dilated left ventricular chamber after aortic valve replacement. Totally 37 patients enrolled between February 2008 and November 2010 with severe chronic aortic regurgitation and extremely dilated left ventricular chamber, who met the echo criteria, that was left ventricular end diastolic dimension > 70 mm or left ventricular end systolic dimension > 55 mm, and were scheduled to the surgery. The 2-dimensional echocardiographic examinations and CMR with late gadolinium-enhancement (LGE) were performed routinely preoperatively. According to the results of CMR, the patients were divided into 2 groups: the LGE positive(+) group and LGE negative(-) group. The association of LGE with event free survival, postoperative cardiac function and postoperative hospital stay time was investigated. Fifteen patients had significant LGE signals in CMR films, while the other twenty-two were silent. All of them received the operative procedures, including aortic valve replacement in 28 cases, Bentall procedure in 3 cases, aortic valve replacement and ascending aorta replacement in 6 cases, and concomitant mitral valve repair in 11 cases. Over a follow-up of 33.6 months, 1-year, 2-year and 3-year event free survival rates in LGE(-) group were 94.7%, 88.4%, and 72.6%, respectively, compared to 80.0%, 48.9%, and 32.6%, respectively in LGE(+) group (χ(2) = 7.244, P = 0.007). The postoperative hospital stay time of LGE(-) group was (9 ± 2) days, which of LGE(+) group was (10 ± 3) days (t = 1.175, P = 0.248). LGE positive signal in CMR films is a potential predictor of persistent cardiac failure after aortic valve replacement for patients with severe chronic aortic regurgitation and extremely dilated left ventricular chamber. It has intimate relationship with malignant arrhythmia and sudden death, which makes it a valuable technique in preoperative evaluation and risk stratification.

The Prognostic Value of Interim PET Scan in Patients with Classical Hodgkin Lymphoma

AbstractAbstract 1529The interim PET scan has prognostic value in pts with cHL. Because the outcome of ptswho have positive interim PET scans was dismal in previous reports, multiple clinical trials are ongoing using the interim PET to guide treatment decisions, but these are mostly non-randomized studies. We performed a retrospective study analyzing the prognostic role of the interim PET scan for predicting event free survival (EFS) for early stage (I and II non-bulky) and advanced stage (II-bulky, III and IV) cHL treated with standard ABVD with or without radiation therapy. This study was approved by the institutional review board.Interim PET results (positive or negative) were collected from the clinical reports of PET scans which were based on visual interpretation. A total of 327 pts diagnosed between 01/2001 and 05/2011, and had interim PET scan after 2 (PET2; n=231) or 3 (PET3; n=96) cycles were reviewed. The median follow up duration of surviving pts was 45 months (range 2–130 months).For pts with advanced stage disease, 5-year EFS rates in PET2-negative (n=79) and PET2-positive (n=20) groups were 75% and 54%, respectively (p=0.027). For pts with low IPS scores (0–2), 5-year EFS rates in PET2-negative (n=60) and PET2-positive (n=15) groups were 77% and 53%, respectively (p=0.02). For pts with high IPS scores (3–7), 5-year EFS rates in PET2-negative (n=19) and PET2-positive (n=5) groups were 69% and 50%, respectively (p=0.76). In pts with early stage disease, 5-year EFS rates in PET2-negative (n=107) and PET2-positive (n=25) groups were 98% and 65%, respectively (p<0.01). PET3 had little prognostic value for EFS for pts with early stage or advanced stage diseases, though the number of pts analyzed was smaller.There have been significant changes in PET technology, methodology, and interpretation criteria. To minimize these factors, we next selected 118 pts whose PET2 were performed between 03/2008 and 05/2011. The PET scans from theres patients were blindly and independently re-reviewed without information on clinical outcome, by two nuclear radiologist based on Deauville criteria. For pts with advanced stage disease, 2-year EFS rates for pts with negative PET2 (n=47) and positive PET2 (n=5) scans were 68% and 60%, respectively (p=0.59). For pts with early stage diseases, 2-year EFS rates for pts with negative PET2 (n=55) and positive PET2 (n=11) scans were 98% and 47%, respectively (p<0.01).In conclusion, this study confirmed that PET2 results remain prognostic, not only for advanced stage disease but more significantly for early stage cHL. However, pts with advanced stage disease whose PET2 was positive had 5-year EFS of 54% (2001–2011), which seems far better than previous reports. Interim-PET guided treatment decisions are not currently recommended outside of clinical trials. Randomized trials will be required to determine whether change of therapy based on PET2 status will improve treatment outcome. [Display omitted] Disclosures:Fanale:MedImmune: Research Funding.

The Outcome of Patients (pts) with Chronic Myeloid Leukemia (CML) Treated with Imatinib Outside of a Clinical Trial or On a Clinical Trial At a Single Institution

Abstract 1693 Background:Outcomes of CML chronic phase (CP) pts treated in clinical trials are frequently perceived to not be representative of those treated outside of clinical trials (Lucas et al, Haematologica 2009; 94: 1362–7). The latter is frequently referred to as “the real world” world experience. Some reports have suggested that outcome of pts treated outside of clinical trials have an inferior outcome. We investigated the outcomes of pts receiving imatinib on and off a clinical trial for CML-CP at a single institution. Methods:We reviewed the medical records of all pts with CML-CP treated at MDACC between 2000 and 2012 to identify pts that received initial therapy with imatinib 400 mg on a clinical trial or as standard therapy outside of a clinical trial (“off protocol” group). Only pts who had not received any prior therapy, or only hydroxyurea, or interferon alpha for less than 1 month, and that initiated on 400 milligram daily dose of imatinib within 6 months of diagnosis were included. Event-free survival (EFS) was measured from the start of treatment to the date of any of the following events: loss of major cytogenetic response (MCyR), loss of complete hematologic response (CHR), transformation to accelerated phase (AP) and blast phase (BP), and death while on imatinib. Transformation-free survival (TFS) was measured from the start of treatment to the date progression to AP/BP during therapy, last follow-up, or death from any cause. Overall survival (OS) was measured until death form any cause at any time. Results:We identified 65 pts treated with imatinib off protocol during the period of interest. During this time 71 pts were treated on clinical trials with imatinib. The median age was 49 yrs (15–79) for pts on clinical trials and 49 yrs (15–84) for those off protocol, respectively. The median follow-up was 125 months (13 to 142) for pts on clinical trials and 51 months (2 to 117) for those off protocol. The overall complete cytogenetic response (CCyR) rates were 84% and 83% for patients treated on and off protocol, respectively. CCyR rates, 12 months after initiation of imatinib, were not different (60% vs 66%, respectively; p=.15). Pts treated on protocol had higher rates of major molecular response (MMR) (79% vs 58%, P=.012) and complete molecular response (CMR = undetectable with sensitivity of at least 4 logs) (42% vs 32%, P=.045) at any time compared to the pts treated off protocol. This is likely due to the longer follow-up for pts on protocol as MMR takes longer to occur. In fact, the MMR rate at 12 months were 30% and 24% in pts treated on and off protocol, respectively (p=.28). Analyzing earlier responses, 3-month rates of MCyR were 71% on protocol and 69% off protocol (p=.82). Corresponding rates at 6 months were 82% and 85%, respectively (p=.68). The 5-year EFS rates were 86% and 84% for on and off protocol patients, respectively. There was also no significant difference in 5-year TFS (96% vs 94%) and OS (90% vs 96%). Conclusion:These results suggest that pts with CML treated outside of a clinical trial may have the same excellent outcome as those treated on a clinical trial provided they are followed with the same rigor. Disclosures:Ravandi:BMS: Research Funding. Cortes:Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding.

Induction Chemotherapy and Conformal Radiation Therapy for Very Young Children With Nonmetastatic Medulloblastoma: Children's Oncology Group Study P9934

P9934 was a prospective trial of systemic chemotherapy, second surgery, and conformal radiation therapy (CRT) limited to the posterior fossa and primary site for children between 8 months and 3 years old with nonmetastatic medulloblastoma. The study was open from June 2000 until June 2006. After initial surgery, children received four cycles of induction chemotherapy, followed by age- and response-adjusted CRT to the posterior fossa (18 or 23.4 Gy) and tumor bed (cumulative 50.4 or 54 Gy) and maintenance chemotherapy. Neurodevelopmental outcomes were evaluated and event-free survival (EFS) results were directly compared with a previous study of multiagent chemotherapy without irradiation (Pediatric Oncology Group [POG] trial 9233). Seventy-four patients met eligibility requirements. The 4-year EFS and overall survival probabilities were 50% ± 6% and 69% ± 5.5%, respectively, which compared favorably to the results from POG 9233. Analysis showed that the desmoplastic/nodular subtype was a favorable factor in predicting survival. Our 4-year EFS rate was 58% ± 8% for patients with desmoplasia. Whereas seven of 10 patients who had disease progression before CRT had primary-site failure, 15 of 19 patients who progressed after CRT had distant-site failure. Neurodevelopmental assessments did not show a decline in cognitive or motor function after protocol-directed chemotherapy and CRT. The addition of CRT to postoperative chemotherapy in young children with nonmetastatic medulloblastoma increased event-free survival compared with the use of postoperative chemotherapy alone. Future studies will use histopathologic typing (desmoplastic/nodular versus nondesmoplastic/nodular) to stratify patients for therapy by risk of relapse.

Randomized Study of Two Chemotherapy Regimens for Treatment of Low-Grade Glioma in Young Children: A Report From the Children's Oncology Group

PURPOSE Surgery is curative therapy for pediatric low-grade gliomas (LGGs) in areas of the brain amenable to complete resection. However, LGGs located in areas where complete resection is not possible can threaten both function and life. The purpose of this study was to compare two chemotherapy regimens for LGGs in children younger than age 10 years for whom radiotherapy was felt by the practitioner to pose a high risk of neurodevelopmental injury. PATIENTS AND METHODS Previously untreated children younger than age 10 years with progressive or residual LGGs were eligible. Children were randomly assigned to receive carboplatin and vincristine (CV) or thioguanine, procarbazine, lomustine, and vincristine (TPCV). Children with neurofibromatosis are reported separately. Results Of 274 randomly assigned patients who met eligibility requirements, 137 received CV and 137 received TPCV. The 5-year event-free survival (EFS) and overall survival (OS) rates for all eligible patients were 45% ± 3.2% and 86% ± 2.2%, respectively. The 5-year EFS rates were 39% ± 4% for CV and 52% ± 5% for TPCV (stratified log-rank test P = .10; cure model analysis P = .007). On multivariate analysis, factors independently predictive of worse EFS and OS were younger age and tumor size greater than 3 cm(2). Tumor location in the thalamus was also associated with poor OS. CONCLUSION The difference in EFS between the regimens did not reach significance on the basis of the stratified log-rank test. The 5-year EFS was higher for TPCV on the basis of the cure model analysis. Differences in toxicity may influence physician choice of regimens.

The comparison between CHOP and R-CHOP in primary gastric diffuse large B cell lymphoma

The combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) plus rituximab is the standard treatment for patients with primary gastric diffuse large B cell lymphoma (DLBCL). However, a few trials comparing CHOP plus rituximab (R-CHOP) with CHOP have been conducted in primary gastric DLBCL. Among 93 consecutive patients receiving CHOP or R-CHOP as a first-line chemotherapy at our institution, 38 patients received CHOP and 55 patients received R-CHOP. With a median follow-up time of 48 months, the complete response (CR) rate, event-free survival (EFS), and overall survival (OS) did not differ between two treatment groups (P = 1.000, P = 0.744, and P = 0.213, respectively). The CR rates were 93.9% for patients receiving CHOP and 92.5% for patients receiving R-CHOP. The 3-year EFS rates were 86.0% for patients receiving CHOP and 81.7% for patients receiving R-CHOP; the 3-year OS rates were 94.7 and 84.7%, respectively. In a multivariate analysis, The CR rate was affected by the number of extranodal involvements (P = 0.011). The EFS and OS rates were affected by the Lugano stage (P = 0.067 and P = 0.008, respectively). High serum level of β₂-microglobulin was associated with worse EFS and OS in patients receiving R-CHOP (P = 0.018 and P = 0.015, respectively). In conclusion, the addition of rituximab was not found to have an impact on patients' outcomes with primary gastric DLBCL. The β₂-microglobulin in primary gastric DLBCL might be able to discriminate the patients' prognosis who are treated with R-CHOP chemotherapy.