Months For Grade Research Articles

RT-05 THE RESULTS OF GAMMA KNIFE RADIOSURGERY WITH BEVACIZUMAB (AVAGAMMA THERAPY) FOR RECURRENT GRADE II/III GLIOMAS

BACKGROUNDFor primary grade II/III glioma, we usually combine radiation therapy and chemotherapy after surgical resection. However, the treatment of recurrent grade II/III glioma is controversial. For lesions that can be safely resected, the second surgery may be optimal, but grade II/III glioma often occurs in or near the eloquent areas, so partial resection is often performed. In such cases, if a second surgery for the recurrent tumor is performed, total resection is often difficult. We have performed gamma knife radiosurgery with concurrent bevacizumab (GKRS with Bev) as salvage therapy for recurrent grade II/III gliomas, which were considered difficult to resect.OBJECTIVETo investigate the outcome of GKRS with Bev for recurrent grade II/III gliomas. <Methods> We retrospectively reviewed initial pathological findings, PFS/OS from GKRS with Bev, and OS from initial treatment for 23 cases receiving GKRS with Bev for recurrent grade II/III gliomas at our institution between August 2013 and March 2019.RESULTSIn the initial pathological findings, grade II were 8 cases (DA: 7, OD: 1), and grade III were 15 cases (AA: 14, AOA: 1). Regarding IDH mutations, in grade II, 3 cases were mutant type, 2 cases were wild type, and 3 cases were unknown. Similarly, in grade III, 5, 6, and 4 cases, respectively. From salvage therapy, PFS was median 6 months in grade II and 8 months in grade III, and OS was median 11 months in grade II and 16 months in grade III. From the initial treatment, OS was median 95 months in grade II, and 38 months in grade III.CONCLUSIONBecause most of our cases were astrocytic tumors, when they relapsed, it seemed that some of them progressed to glioblastoma. Even in these severe cases, GKRS with Bev can play an important role as salvage therapy.

Clinical Outcomes of Proton Beam Re-Irradiation for Recurrent Gliomas

Despite improved molecular subtyping, overall prognosis of recurrent gliomas remains poor. Salvage re-irradiation (reRT) for recurrence can result in significant local control and proton beam radiotherapy (PBRT) offers a potential advantage due to lower integral dose to previously irradiated tissue. There is limited data on PBRT reRT outcomes. Twenty-two consecutive patients (median age 49, range 24-73) who received PBRT reRT for recurrent glioma between 2013 and 2018 were analyzed. The majority underwent PBRT reRT for recurrent Grade IV glioma (50%, 41% for WHO Grade III, and 9% for WHO Grade II). Prior to PBRT reRT, patients had a median of 1 surgery (range 1-4) and 2 systemic therapy regimens (range 1-5); 82% and 18% had 1 and 2 prior courses of RT, respectively, with a median duration of 27 months (range 7-232) prior to PBRT. Median total prior RT dose was 60 Gy (range 50.4-119.4). PBRT reRT was delivered using 3D conformal (50%), pencil beam (45%) scanning or a mix (5%). Planned reRT dose was a hypofractionated regimen in 45% of patients with doses of 30-40 Gy (RBE) in 10-15 fractions while the remaining 55% had doses of 45-60 Gy (RBE) in 25-33 fractions. Kaplan-Meier was used to determine local failure (LF), intracranial distant failure (DF), and overall survival (OS) from start of PBRT. Proportional hazards modeling was used to assess clinical predictors of these outcomes. The median OS post PBRT reRT was 11 months (6 months for Grade IV, 11 months for Grade III). Grade IV tumors had significantly poorer local control with a median time to LF after reRT of 6 months (p=0.02). Median time to DF was 7 months with no significant differences by WHO grade. Tumors with 1p19q codeletion (HR=0.1, p=0.02) and increased duration from prior RT (HR=0.98, p=0.04) were associated with improved OS post PBRT reRT while IDH1 mutant status trended toward better OS (HR=0.3, p=0.06). No molecular tumor markers were found to be associated with LF or DF, including MGMT methylation status. The number of prior lines of systemic therapy was also not associated with OS, LF, or DF. Patients had large reRT volumes with median PTV of 190 cc (range 3-676). PTV size was not prognostic of LC but hypofractioned courses trended towards poorer LC (HR 4.2, p=0.08) with no difference in DF (p=0.97) or OS (p=0.12). Two patients (10%) terminated PBRT early, one due to a mechanical fall and subsequent subdural hematoma; the other progressed during PBRT and required urgent debulking surgery. Three patients (14%) developed symptomatic radiation necrosis at 2, 2, and 12 months post reRT that were treated with bevacizumab and high dose steroids. PBRT reRT was generally well tolerated with low rate of radiation necrosis and promising local disease control for recurrent glioma. While tumor grade and 1p19q codeletion status were predictive of OS, local control after reRT was associated with tumor grade and not tumor molecular markers. Further study is needed to elucidate which patients would most benefit from proton reRT.

Single center experience: Management of metastatic appendiceal cancer with peritoneal carcinomatosis.

e15103 Background: Appendiceal tumors constitute only 1% of intestinal malignancies with no established standard of care due to their relative rarity. Timing, preferred regimen and utility of chemotherapy in this malignancy are among the many questions that still remain unanswered. Methods: Retrospective chart review of patients treated for appendiceal carcinoma at our institution who had slides available for pathology review (96 patients met this criteria). Results: Mean age at diagnosis was 55.8 years. 84% were Caucasian and 13.8% were African American, 19.8% had a family history of colon cancer. Mucinous adenocarcinoma was the most frequent subtype (70.8%) followed by colonic (8.3%), signet ring, goblet cell and mixed. 63 had cytoreductive surgery, 63 had HIPEC, 23 had neo-adjuvant and 41 patients had adjuvant chemotherapy. 30 patients received bevacizumab with first line. 6 of 43 patient with CCR0, 0 of 10 patients with CCR1 and 1 of 10 patients with CCR2 died during follow-up. Eventually, 17 patients had second surgery (debulking in 6, debulking+HIPEC in 11). 52 patients had progression and this was most frequently diagnosed on surveillance imaging (73.1%.) Mean time to progression (TTP) was 39.3 months (8-432 months) and second progression was 62.4 months (21.5-177.6 months.) Median time from surgery to progression was 31.6 months (9.6-417.5 months). TTP and OS are not associated with age and although mean survival was numerically greater in women (303.9 months) than men (220.5 months), this was not statistically significant (p=0.903). Pathologic grade 1 had a longer time to progression compared to grade 2 and 3 (176.9 months versus 55.5 and 59.1 months, p= 0.001). There was a significant difference in TTP based on tumor differentiation (p=0.019) with 191.5 months, 45.3 months and 67.2 months in well, moderate and poorly differentiated respectively. Survival by pathologic grade approached significance (p=0.067), 336.3 months, 171.9 months, 129.1 months in grade 1, 2 and 3 respectively. Conclusions: 80% patients have peritoneal carcinomatosis at diagnosis and for every 1 increase in PCI, the risk of progression increases by 4.8% but this does not affect survival. FOLFOX/ Xelox in first line was associated with longer time to progression. [Table: see text]

A Methionine PET Targeting for Gamma Knife Radiosurgery used to Treat Recurrent Malignant Gliomas at Inoperable Stage

Purpose: The current study investigates the usefulness of metabolic positron emission tomography (PET) imaging (in particular with 11C-methionine (MET)), for target definition during gamma knife radiosurgery (GKRS) of locally multirecurrent malignant glioma at inoperable stage. Patients and Methods: We retrospectively evaluated the results of GKRS with MET-PET targeting for 24 adult focally recurrent inoperable malignant gliomas treated at the Erasme Gamma Knife Center between 2007 and 2018. We evaluated the type of tumour progression (local vs remote), progression-free survival (PFS), overall survival (OS) and toxicity after MET-PET targeting of GKRS for these 24 patients. Results: The median PFS after GKRS for the 24 patients with malignant gliomas was 5.5 (2-46) months and 4.5 (3-10), 4.5 (2-8) and 13.5 (2-46) months for glioblastoma, anaplastic glioma and grade II glioma patients, respectively. The median OS from the GKRS procedure for patients with recurrent glioblastomas (n=12) was 18 (6-45) months, 8 (6-184) months for anaplastic gliomas (n=6), and 22 (16-65) months for grade II gliomas (n=6). All patients with grade III and II multirecurrent gliomas (n=12) showed an early favourable local metabolic response, while this response was observed only in 6/12 of the glioblastomas. However, the majority (9/12=75%) of these grade II/III glioma patients further developed new lesions. GKRS treatment was associated with diverse chemotherapies in more than 50% (13/24) of cases. Post-GKRS radio-necrosis was observed in only one patient. Conclusion: Based on a limited series of 24 patients, our study shows, for the first time, the GKRS-induced metabolic response in focally recurrent inoperable malignant gliomas. GKRS could be part of the multidisciplinary approach for multirecurrent malignant gliomas that cannot be anymore treated by surgery.

Real-world management and survival outcomes of patients with newly diagnosed gliomas from a single institution in China: A retrospective cohort study

Background and Aim: Guidelines recommend adjuvant treatment for patients with high-grade gliomas and low-grade gliomas with high risk of progression. In clinical practice, however, treatments may not conform to these suggested guidelines. In this study, we reviewed the treatments and outcomes in patients with gliomas at Sun Yat-Sen University Cancer Center (SYSUCC), China. Materials and Methods: Medical records and radiologic images of 1215 glioma patients who underwent surgery at the center from 2000 to 2017 were retrospectively reviewed, and their clinicopathological characteristics, treatment method, and overall survival (OS) were analyzed. The study was approved by the Ethics Committee of SYSUCC on February 20, 2019 (approval No. GZR2019-219). Results: A total of 1001 patients diagnosed with glioma (initially World Health Organization 2007 criteria, then 2016 criteria) were enrolled, including 90 patients with Grade I, 307 Grade II, 239 Grade III, and 365 Grade IV gliomas. A total of 331 of 604 patients with high-grade glioma (54.8%) and 159 of 397 with low-grade glioma (40.1%) received postsurgical radiotherapy, and 285 patients with high-grade tumors (47.1%) and 80 with low-grade tumors (20.2%) received adjuvant chemotherapy. The median OS was 17.5 months for Grade IV and 43.1 months for Grade III gliomas. The median OS of patients with low-grade glioma was not reached. The 5-year survival rates of patients with Grades I, II, III, and IV gliomas were 94.7%, 73.7%, 45.7%, and 18.6%, respectively. Multivariate analysis identified onset age, preoperative seizure, tumor location, pathological subtype, resection extent, and postsurgical treatment as independent predictors of OS in patients with high-grade gliomas. Patients with high-grade glioma who received postsurgical treatment had better survival than those without adjuvant therapy (Grade III: 52.6 vs. 20.3 months, P = 0.012; Grade IV: 22.6 vs. 12.1 months, P

Status Gizi dan Perkembangan Motorik Halus Anak Usia 48 – 60 Bulan

&lt;p&gt;&lt;em&gt;Background: Fine motor development in infants and young children is very important. Impaired motor coordination is known to affect 1 in 20 school-aged children. Objective: The study aims to describe the nutritional status and fine motor development of children aged 48-60 months in grade A students of PAUD Pertiwi Metro City. Methods: This study uses a descriptive design to describe the nutritional status and fine motor development of children aged 48-60 months. The study population was students of class A PAUD Pertiwi Metro City with a sample of 50 people. The sampling technique uses accidental sampling. Results: The results showed a picture of 12% of children with underweight nutritional status, there were 6% of children with normal motor development. There are children with normal nutritional status of 93.2% with normal fine motor development. Conclusion: The study concluded that the nutritional status of children has a tendency to support fine motor development in children aged 48 - 60. It is necessary for the school to collaborate with parents to monitor children's nutritional status and motor development routinely so that children can pass each developmental task according to their age.&lt;/em&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;

Perl's Stain Grade in the Bone Marrow Aspirate Correlates with Overall Survival in Low Risk Myelodysplastic Patients

BackgroundMyelodysplastic syndromes (MDS) are heterogeneous group of acquired clonal hematopoietic stem cell disorders characterized by atypical stem cells maturation and genetic instability leading to an enhanced risk of progression to acute myeloid leukemia. Low risk MDS patients have a lower probability to evolve in leukemia but are commonly characterized by dyseritropoiesis. These patient are incline to long term accumulation of iron in the organs due mostly to red blood cell transfusion (RBC) but iron overload may also occur in MDS patients who do not receive RBC transfusions due to the ineffective erythropoiesis. It is well known the effect of oxidant-mediated tissue's injury through the formation of free toxic iron species in the liver and heart site, but recent knowledges assumes that this mechanism is effective also in the bone marrow nice, where oxidative stress seems to impaired the haematopoietic stem cells growth. At this moment microscopic examination of the stainable iron in the bone marrow is considered the gold standard for determining the iron stores. The effect of bone marrow's iron overload on overall survival in the low risk MDS has been a matter of unresolved debate. We aimed to investigate the predictive value of bone marrow iron accumulation as demonstrated by Perl's staining on outcome in such patients.DesignWe retrospectively analyzed all low risk,intermediate-I MDS patients who had diagnosed in our institution in the last 20 years (since 1998). Diagnosis of MDS was made according to WHO criteria. Patients were stratified based on International Prognostic Scoring System (IPSS). Patients had undergone bone marrow aspiration as part of the diagnostic work up for their MDS. Two different experienced hematologist analyzed all samples. Bone marrow aspiration slides with at least seven fragments were considered suitable. Perl's Prussian blue stain was used to stain bone marrow, assessed by modified Gale's grading (Tab. 1) and then correlated with outcome.Patients and methodsMarrow staining of one hundred and fourteen consecutive MDS patients were revised and analyzed. Median age was 70 years (range 32-93). Eighty three patients were IPSS low- risk and 30 Intermediate I. All patients were evaluated for bone marrow iron stores with Perl's stain. Twenty-seven patients had grade 1 (+), 31 grade 2 (++) and 56 grade 3 (+++). Patients had never or minimally received RBC . None of these patient had received iron chelation before marrow examination. Probability of overall survival (OS) was estimated by the Kaplan-Meier method and the significance was assessed by the log-rank test.Results20-year OS was significantly lower in patients with higher Perl's score (median = 80 ±7 months in grade 3; median = 70 ±17 months in grade 2; median = 144 ±18 months in grade 1 , P=0.011); Fig. 1ConclusionsWe evaluated retrospectively the bone marrow aspirate from 114 consecutive new MDS low-risk, Intermediate-I IPSS patients with Perl's stain for iron detection. Although Perl's grading is a qualitative method, it is still the gold standard to detect iron storage in the bone marrow. Our results correlate Perl's stain at diagnosis with long term outcome in MDS patients. We show how higher grade of iron storage at diagnosis can impact on outcome in these patients. We conclude that Perl's stain, together with Ferritin and blood transfusional burden could be another marker at diagnosis of iron-related toxicity that predict overall survival. DisclosuresPilo:Novartis Italy: Honoraria. Angelucci:Jazz Pharmaceuticals Italy: Other: Local ( national) advisory board; Vertex Pharmaceuticals Incorporated (MA) and CRISPR CAS9 Therapeutics AG (CH): Other: Chair DMC; Roche Italy: Other: Local (national) advisory board; Novartis: Honoraria, Other: Chair Steering Comiittee TELESTO Protocol; Celgene: Honoraria, Other: Chair DMC.

The albumin‐bilirubin grade uncovers the prognostic relationship between hepatic reserve and immune dysfunction in HIV‐associated hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a leading cause of liver-related mortality in people living with HIV, where co-infection with hepatotropic viruses accelerates the course of chronic liver disease. To evaluate whether the albumin-bilirubin (ALBI) grade, a more accurate marker of liver dysfunction in HCC, might identify patients with progressive liver dysfunction in the context of HIV/hepatitis co-infection. Using uni- and multi-variable analyses, we studied the albumin-bilirubin grade as a predictor of overall survival (OS) in a large, multi-center cohort of patients with HIV-associated HCC recruited from 44 centres in 9 countries within the Liver Cancer in HIV study group. Patients who underwent liver transplantation were excluded. A total of 387 patients, predominantly HCV co-infected (78%) with balanced representation of all Barcelona Clinic Liver Cancer (BCLC) stages (A=33%, B=18%, C=37%, D=12%) were recruited. At HCC diagnosis, 84% had been on anti-retrovirals for a median duration of 8.8years. The albumin-bilirubin grade identified significant differences in median survival of 97months for grade 1 (95% CI 13-180months), 17months for grade 2 (95% CI 11-22months) and 6months for grade 3 (95% CI 4-9months, P<.001). A more advanced albumin-bilirubin grade correlated with lower CD4 counts (464/373/288 cells/mm3 for grades 1/2/3) and higher HIV viraemia (3.337/8.701/61.845 copies/mL for grades 1/2/3, P<.001). In this large, multi-center retrospective study, the albumin-bilirubin grade highlights the interplay between liver reserve and immune dysfunction as prognostic determinants in HIV-associated HCC.

Early Identification of Reading Difficulties: A Screening Strategy that Adjusts the Sensitivity to the Level of Prediction Accuracy.

Early screening for reading difficulties before the onset of instruction is desirable because it allows intervention that is targeted at prevention rather than remediation of reading difficulties. However, early screening may be too inaccurate to effectively allocate resources to those who need them. The present study compared the accuracy of early screening before the onset of formal reading instruction with late screening six months into the first year of instruction. The study followed 164 Danish students from the end of Grade 0 to the end of Grade 2. Early screening included measures of phonemic awareness, rapid naming, letter knowledge, paired associate learning, and reading. Late screening included only reading. Results indicated that reading measures improved substantially as predictors over the first six months of Grade 1, to the point where late reading measures alone provided as much information as the early measures combined. In the light of these results and a less than perfect early screening accuracy, a new strategy for screening is introduced and discussed. The strategy proposes multi-point screening with gradually increasing sensitivity to strike a balance between manageable screening procedures and outcomes and early identification of students who are most likely in need of extra resources. Copyright © 2017 John Wiley & Sons, Ltd.

Prognostic factors for tumor recurrence in endometrioid endometrial cancer stages IA and IB.

Risk grouping for treatment and follow-up strategy of early stage endometrial cancer is confusing to apply in clinical conditions. We investigated the stage-based prognostic factors for tumor recurrence in stage I endometrial cancer with endometrioid histology (EEC).The medical records of women diagnosed with endometrial adenocarcinoma between 1993 and 2013 were retrospectively reviewed. In 521 patients with International Federation of Gynecology and Obstetrics (FIGO) stage I EEC were included. The baseline patient characteristics were analyzed with the chi-square test and Fisher's exact tests. A multivariate analysis with a Cox proportional hazard model and logistic regression were performed to identify the prognostic factors for recurrence-free survival (RFS) in FIGO stage I EEC.The median follow-up period for the included patients was 74.6 months (3.1–264.9 months). Tumor recurrence occurred in 30 patients (5.8%) with a median time span of 22.85 months (2.2–124.7 months). Only 2 factors among the conventional adverse risk factors, including myometrial invasion and histologic grade, affected tumor recurrence in stage I EEC (P = .003 and P = .003, respectively). Myometrial invasion was an independent prognostic factor for RFS in stage IA EEC via multivariate analysis (P = .005). In stage IB EEC, the histologic grade was an independent prognostic factor for RFS. The median RFS of stage IB EEC was 156.0 months in grade 1, 120.0 months in grade 2, and 105.9 months in grade 3 (P = .006).Within stage I EEC, the prognostic factors for tumor recurrence were different between stages IA and IB. Myometrial invasion comprised the prognostic factor in stage IA, whereas the histologic grade comprised the prognostic factor in stage IB.

Effectiveness of endoscopic balloon dilatation in grade 2a and 2b esophageal burns in children

Purpose: To evaluate the predictability of the initial endoscopic evaluation of the effectiveness of endoscopic balloon dilatation (EBD) in childhood esophageal strictures caused by corrosive ingestion.Material and methods: Medical records of 635 endoscopies caused by corrosive ingestion between January 2000 and December 2015 in children between the ages of 0 and 18 years were retrospectively analyzed. Among them, five children with grade 2a and 15 with grade 2 b who developed esophageal strictures were evaluated for the effectiveness of endoscopic balloon dilatation.Results: The stricture rate was 5/136 (3.6%) in grade 2a and 17/25 (68%) in grade 2 b esophageal burns. Strictures with grade 2a burn had seven (1–10) EBD sessions, and grade 2 b had 8.8 (1–30) EBD sessions. For grade 2a burns, the treatment period was 15 months and 18.8 months for grade 2 b burns. Three patients with grade 2 b and two patients with grade 2a are still on the EBD program.Conclusion: Initial endoscopy for caustic ingestion and esophageal injury grading may help to provide healthcare givers with information about future stricture formation and management.

Risk Factors for the Development of and Outcomes of Patients Who Develop Severe Cytokine Release Syndrome after Peripheral Blood Haploidentical Donor Transplant

Background:Allogeneic hematopoietic cell transplantation is a cornerstone of therapy for hematologic malignancies and often a patient's only curative intent treatment. Following development of post-transplant cyclophosphamide (PTCy) regimens, the use of haploidentical hematopoietic cell transplantation (haplo-HCT) has expanded. While overall outcomes for haploidentical transplantation appear to be excellent, its novel approach brings toxicities that are particular to its biological and clinical milieu. We recently described occurrence of severe cytokine release syndrome (CRS) after haplo-HCT. We further reported that severe CRS was associated with poor clinical outcomes, including transplant related mortality (TRM), overall survival (OS), and neutrophil engraftment (Abboud et al, BBMT, 2016). However, the factors predicting the occurrence of and long-term outcomes of patients who develop severe CRS after haplo-HCT is currently not known.Objective: To describe our clinical experience with CRS in an expanded cohort of haplo-HCT patients, its implication on clinical outcomes and elucidation of possible risk factors for the development of severe CRS.Patients and Methods: We performed a retrospective review of patients who had undergone peripheral blood T-Cell replete haplo-HCT with PTCy from July 2009 through March 2016 at our institution. A total of 137 patients were identified, 51% (74) were male, with a median age at transplant of 52 (19-73), a total of 40% (57) had active disease at the time of transplant. The most common diagnosis was AML (93 pts), followed by ALL (16 pts) and MDS (15 pts). Thirty-one percent (44 pts) had undergone prior transplant. In grading CRS, we used our approach modified from by Lee et al (Blood, 2014). Twenty-two patient, donor and disease characteristics were examined to identify predictors for the development of severe CRS.Results:One hundred and twenty-four (90%) of patients met criteria for CRS, and 26 (19%) suffered from severe (grade 3-4) CRS. Virtually all patients (99%) with CRS suffered from fevers. Patients with severe CRS had a significant delay in neutrophil (p < 0.0001) and platelet (p < 0.0001) engraftment compared to the patients who developed mild or no CRS (Figure 1A and 1B). Severe CRS was also associated with a high early transplant related mortality; the rate of death before post-transplant day 28 was 6.9 times higher for patients with grade 3-4 CRS compared with those with mild CRS (p < 0.0001, Figure 1C). Consistent with these findings, the development of severe CRS was associated with extremely poor survival. Median survival was 3 months for grade 3-4 CRS, 15 months for grade 1-2 CRS, and 13 months for no CRS. One-year OS was 4% for grade 3-4 CRS, 55% for grade 1-2 CRS, and 50% for no CRS (Figure 1D). There was no difference in the cumulative incidence of relapse, acute graft versus host disease, and chronic graft versus host disease (data not shown). A total of nine patients received Anti-IL-6 Therapy with tociluzimab (4 mg/kg of actual body weight), 4 of which suffered from severe CRS.In terms of predictive factors, the development of severe CRS was associated with disease risk index (p=0.037), HCT-CI score (p=0.005) and presence of a previous transplant (p=0.026) by univariate analysis. Risk and severity of CRS did not differ by age, ABO mismatch, age, CMV status of donor, donor sex, T-cell or CD34 cell dose. There was no difference in rates of CRS among patients in remission or with active disease at the time of transplant.Conclusions: Severe CRS after peripheral blood haplo-HCT is associated with high early TRM, poor OS and delayed neutrophil and platelet engraftment. Furthermore, patients with high DRI, high HCT-CI and prior HCT are at a higher risk for the development of severe CRS after haplo-HCT. We have previously shown the safety and potential efficacy of using anti-IL-6 therapy in these patients. Our current results suggest potential benefit to targeting this pathway prophylactically in patients at high risk for the development of severe CRS. [Display omitted] [Display omitted] DisclosuresDiPersio:Incyte Corporation: Research Funding. Abboud:Gerson and Lehman Group: Consultancy; Merck: Research Funding; Teva: Research Funding, Speakers Bureau; Novartis: Research Funding; Pfizer: Research Funding; Seattle Genetics: Research Funding; Alexion: Honoraria; Baxalta: Honoraria; Pharmacyclics: Honoraria; Takeda: Honoraria; Cardinal: Honoraria. Fehniger:Affimed: Consultancy; Celgene: Research Funding; Fortress Biotech: Consultancy.

Somatostatin receptor-targeted radionuclide therapy for progressive meningioma: benefit linked to 68Ga-DOTATATE/-TOC uptake.

The prognosis of patients with progressive meningioma after failure of surgery and radiotherapy is poor. We retrospectively evaluated the safety and efficacy of somatostatin-receptor (SSTR)-targeted radionuclide therapy (177Lu-DOTATATE [n = 16], 90Y-DOTATOC [n = 3], or both [n = 1]) in patients with progressive, treatment-refractory meningiomas (5 World Health Organization [WHO] grade I, 7 WHO grade II, 8 WHO grade III) and in part multifocal disease (17 of 20 patients). SSTR radionuclide treatment (median of 3 treatment cycles, median administered dose/cycle 7400 MBq) led to a disease stabilization in 10 of 20 patients for a median time of 17 months. Stratification according to WHO grade showed a median progression-free survival (PFS) of 32.2 months for grade I tumors, 7.2 for grade II, and 2.1 for grade III. PFS at 6 months was 100% for grade I, 57% for grade II, and 0% for grade III. Median overall survival was 17.2 months in WHO grade III patients and not reached for WHO I and II at a median follow-up of 20 months. In the analysis of single meningioma lesions, maximal and mean standardized uptake values in pretherapeutic 68Ga-DOTATOC/-TATE PET/CT were significantly higher in those lesions with radiographic stability after 6 months. In line with this, high expression of SSTR via immunohistochemistry was associated with PFS >6 months. SSTR-targeted radionuclide treatment has activity in a subset of patients with meningioma. Expression of SSTR via immunohistochemistry or radionuclide uptake might serve as a predictive biomarker for outcome to facilitate individualized treatment optimization in patients with uni- and multifocal meningiomas.

Prediction of word recognition in the first half of grade 1

Early detection of reading problems is important to prevent an enduring lag in reading skills. We studied the relationship between speed of word recognition (after six months of grade 1 education) and four kindergarten pre-literacy skills: letter knowledge, phonological awareness and naming speed for both digits and letters. Our sample consisted of 178 pupils divided over seven classes. In agreement with the literature, we found that all four kindergarten tests were related to speed of word recognition in grade 1. We also performed a multiple regression analysis with a set of background variables and the four kindergarten tests. The model explained 53% of the variance in speed of word recognition. However, only letter knowledge and naming speed for digits had a significant direct effect. Our conclusion is, nevertheless, that all four kindergarten tests should be used to identify children at risk for reading problems.

Chemotherapy-induced neutropenia as a prognostic factor in patients with unresectable pancreatic cancer.

We conducted a retrospective cohort study to examine whether neutropenia could be an indicator of good prognosis in patients treated with gemcitabine (GEM) for unresectable pancreatic cancer. A total of 178 patients with unresectable pancreatic cancer, who were treated with first-line (n = 121) or second-line (n = 57) GEM, were included in our analyses. A Cox proportional hazard model was used to examine the effect of the grade of GEM-induced neutropenia on prognosis. Furthermore, the difference in survival time for each grade was assessed using a log-rank test. In the first-line population, the hazard ratios of patients with grade 2 or grade 3 neutropenia compared with the ratios of those without neutropenia (grade 0) were 0.43 (95% CI 0.27-0.70) and 0.37 (0.21-0.65), respectively (p < 0.05). The median survival time (MST) was 3.8 months for grade 0, 9.4 months for grade 2, and 10.1 for grade 3. Landmark analysis of the second-line population revealed a hazard ratio of 0.52 (0.30-0.82) for grade 1 and 0.49 for grade 2 (0.28-0.72) (p < 0.05). MST was 1.3 months for grade 0, 4.7 months for grade 1, and 4.6 months for grade 2. We found that neutropenia grade was an indicator of good prognosis in patients treated with first-line and second-line GEM for unresectable pancreatic cancer. A prospective study should be performed to examine whether dosage adjustment using neutropenia grade as an indicator would improve prognosis.

MNGO-20SOMATOSTATIN RECEPTOR-TARGETED RADIONUCLIDE THERAPY FOR PROGRESSIVE MENINGIOMA

BACKGROUND: There is no standard of care beyond surgery and radiotherapy for patients with progressive meningioma. Somatostatin receptors have been proposed as therapeutic targets. However, systemic administration of somatostatin analogs has shown only limited efficacy. Somatostatin receptor-targeted radionuclide therapy represents a novel treatment option for progressive meningioma. METHODS: In a retrospective analysis, we assessed safety and efficacy of somatostatin receptor-targeted radionuclide therapy (90Y-DOTATOC (n = 3) or 177Lu-DOTATATE (n = 16) or both (n = 1)) in 20 patients with progressive, treatment-refractory meningiomas (histological grading: 5 WHO grade I, 7 WHO grade II, 8 WHO grade III meningiomas). Changes in the growth rate before and after therapy were assessed by volumetric analysis where applicable. RESULTS: Somatostatin receptor radionuclide treatment was well tolerated. A median of 3 treatment cycles were given (median administered dose per cycle 7400 MBq). Response to treatment was moderate with disease stabilization in 10 of 20 patients for a median time of 17 months. Median progression-free survival (PFS) for all patients was 5.4 months, 32.2 months for grade I, 7.6 months for grade II and 2.1 months for grade III meningiomas. PFS correlated inversely with tumor grade. Median overall survival from start of intervention was not reached at a medium follow-up time of 20 months. Volumetric measurement showed a reduction of more than 25% of growth rate after therapy in 4 of 8 patients analyzed. Correlation between intensity of somatostatin receptor expression of single meningioma lesions via 68Ga-DOTATOC/-TATE-PET/CT or via immunohistochemistry and outcome was investigated. CONCLUSION: Somatostatin receptor-targeted radionuclide treatment is a safe therapy option in patients with progressive meningioma and is effective in a subset of patients with WHO grade I and grade II meningioma requiring systemic therapy, but might have limited efficacy in patients with WHO grade III meningioma.

EPID-09IMPROVED SURVIVAL OF LOW-GRADE GLIOMA PATIENTS (1999-2010) DESPITE DECREASED UTILIZATION OF RADIATION THERAPY: A SEER-BASED ANALYSIS.

BACKGROUND: The survival trends and the patterns of clinical practice pertaining to radiation therapy and surgical resection for WHO grade I, II, and III astrocytoma patients remain poorly characterized. METHODS: Using the Surveillance, Epidemiology and End Results (SEER) database, we identified 2497 grade I, 4113 grade II and 2755 grade III astrocytomas during the period of 1999-2010. Time-trend analyses were performed for overall survival (OS), radiation treatment (RT), and the extent of surgical resection (EOR). RESULTS: While overall survival of grade I astrocytomas remain unchanged during the study period, we observed improved overall survival for grade II and III astrocytoma patients (Tarone-Ware p < 0.05). The median survival increased from 44 to 57 months and from 15 to 24 months for grade II and III astrocytoma patients, respectively. The differences in survival remained significant after adjusting for pertinent variables including age, ethnicity, marital status, sex, tumor size, tumor location, EOR, and RT status. The pattern of clinical practice in terms of EOR for grade II and III astrocytoma patients did not change significantly during this study period. However, there was decreased RT utilization as treatment for grade II astrocytoma patients after 2005. CONCLUSION: Results from the SEER database indicate that there were improvements in the overall survival of grade II and III astrocytoma patients over the past decade. Notably, the improved survival for grade II astrocytoma was achieved despite an overall decrease in up-front radiation therapy. These results bear significant implications in terms of neuro-cognitive preservation in terms of delaying radiation therapy for grade II glioma patients.

Survival trends of grade I, II, and III astrocytoma patients and associated clinical practice patterns between 1999 and 2010: A SEER-based analysis.

The survival trends and the patterns of clinical practice pertaining to radiation therapy and surgical resection for WHO grade I, II, and III astrocytoma patients remain poorly characterized. Using the Surveillance, Epidemiology and End Results (SEER) database, we identified 2497 grade I, 4113 grade II, and 2755 grade III astrocytomas during the period of 1999-2010. Time-trend analyses were performed for overall survival, radiation treatment (RT), and the extent of surgical resection (EOR). While overall survival of grade I astrocytoma patients remained unchanged during the study period, we observed improved overall survival for grade II and III astrocytoma patients (Tarone-Ware P < .05). The median survival increased from 44 to 57 months and from 15 to 24 months for grade II and III astrocytoma patients, respectively. The differences in survival remained significant after adjusting for pertinent variables including age, ethnicity, marital status, sex, tumor size, tumor location, EOR, and RT status. The pattern of clinical practice in terms of EOR for grade II and III astrocytoma patients did not change significantly during this study period. However, there was decreased RT utilization as treatment for grade II astrocytoma patients after 2005. Results from the SEER database indicate that there were improvements in the overall survival of grade II and III astrocytoma patients over the past decade. Analysis of the clinical practice patterns identified potential opportunities for impacting the clinical course of these patients.

Grade and Prognosis in Localized Primary Angiosarcoma

BackgroundPrimary angiosarcoma of the breast (PAOB) is rare and institutional series have provided conflicting data on the effect of grade on prognosis. Patients and MethodsUsing a case listing session of Surveillance, Epidemiology, and End Results (SEER) 18 (1973-2010) we examined outcomes for patients with PAOB. Analyses were conducted with SEER*Stat 8.1.2, Microsoft Excel 2007, and GraphPad Prism 6. Comparisons were made using the Fisher exact test and log rank test (Mantel–Cox); P values were 2-sided. ResultsTwo hundred twenty-six women with PAOB were identified; median age was 49 (range, 15-107) years and 82% (185) were white. Seventy-two percent (162) had localized disease, 15% (34) regional disease, 7% (16) distant disease, and 6% (14) had unknown staging. Fourteen percent (32) had Grade 1, 24% (55) Grade 2, 30% (68) Grade 3 disease, and grade was unknown in 32% (72) of patients. Median overall survival (OS) for patients with localized, regional, and distant disease was 172, 24, and 16 months, respectively (P < .001). Median OS for patients with localized Grade 1 and 2 disease was not reached versus 36 months for Grade 3 disease (P < .001); 3-year OS was 89% (78) versus 47% (32). There was a strong trend for patients with Grade 3 disease to undergo mastectomy (44%, n = 30 vs. 23%, n = 20; P = .070) and 24% (55) of all patients received radiation. Radiation did not improve survival for localized Grade 1 and 2 disease (P = .676), or Grade 3 disease (P = .589); surgery and grade subgroups were too small for meaningful comparisons regarding radiation. ConclusionHistologic grade is a significant predictor of survival for patients with localized PAOB. Regardless of grade, adjuvant radiation did not confer a survival benefit for patients with localized disease.

Survival Following Stereotactic Radiotherapy for Recurrent High Grade Gliomas

We aimed to report our stereotactic radiotherapy experience with Cyberknife (Accuray, Inc., Sunnyvale, CA, USA) for patients with recurrent high grade glial tumor. Forty-two patients with histologically proven malign glioma (30 glioblastoma, 12 anaplastic astrocytoma) and also treated with previous conventional fractioned radiotherapy underwent stereotactic radiotherapy via Cyberknife for their recurrent tumor in Ankara Oncology Hospital between July 2009-and September 2012. The median follow up time was 30 months (range, 8-144 months) after diagnosis and 10 months (range, 1-38 months) from stereotactic radiotherapy (SRT). The median survival from SRT are 8 months for glioblastoma patients and 11 months for grade 3 malign glioma patients (p= 0.157). The median survival from SRT are 9 months and 11 months in patients given chemotherapy and not given, respectively (p= 0.436). The median survival from SRT are 10 months in patients reoperated and 9 months not reoperated ( p= 0.827). Stereotactic radiotherapy is an effective treatment modality in patients with recurrent glial tumor.