Practical Applications of The Low-Risk Anomaly: How Much Is a Good Risk Estimate Worth?

Background: Overall survival (OS) for childhood ALL treated on contemporary protocols is now > 90%. For low risk patients the risk of treatment related mortality (TRM) is now similar to the risk of death due to disease relapse. The only way to improve TRM and morbidity in this group is to identify even lower risk patients and reduce therapy. We analysed outcomes for patients with low risk MRD at end of induction (EOI) therapy treated on UKALL 2003, to identify a very low risk group who could potentially benefit from protocols that further reduce TRM. Methods: UKALL 2003 trial recruited 3126 patients aged 1-25 years with Philadelphia-negative ALL between Oct 1, 2003, and June 30, 2011. Treatment was initially stratified based on NCI risk and cytogenetic results. Subsequent treatment was directed by MRD from bone marrow (BM) measured using EuroMRD approved real-time quantitative PCR method for immunoglobulin and T-cell receptor gene rearrangements at EOI therapy. Analysis was performed on the 2666 patients with available MRD results and focused on patients with low risk MRD combined with other patient characteristics - cytogenetic risk group, white cell count (WCC) and age to identify those subgroups with extremely good event free survival (EFS). Low risk MRD at EOI was defined a level <0.005%. Patients with MRD ≥ 0.005% were considered high risk. Good risk cytogenetics included the presence of ETV6-RUNX1 or high hyperdiploidy. Results: Overall 52% (n=1391) of patients had MRD < 0.005% with the remaining 48% (n=1275) of patients with MRD ≥ 0.005%. 5yr OS 97.6 (95% CI 96.6-98.3) vs. 89.1% (87.2-90.7, p<0.0001) and 5yr EFS 94.4 (93.1-95.6) vs. 83.6% (81.4-85.5, p<0.0001). 53% (n=1407) of the patients with MRD results available had good risk cytogenetics, of which 60% (n=843) had MRD<0.005%. This group (with low risk MRD and good risk cytogenetics) makes up 31.6% of the whole trial cohort and has 5yr EFS 96.0% (94.5-97.3) and 5yr OS 98.9% (97.9-99.4). The outcome was similar irrespective of NCI high risk features (i.e. WCC>50 / age>10yrs). Long term survival remained excellent with 10 year EFS 93.9% (OS 98.2%). There were 32 relapses in the low risk MRD/ good risk cytogenetics group (relapse sites: 11 BM, 7 combined BM and central nervous system (CNS), 3 BM + other site, 6 isolated CNS and 5 other site, non BM/CNS), giving an overall relapse rate of 3.8% with a salvage rate of 81%. The relapse death rate was 0.7% (n=6) with TRM of 0.8% (n=7). The low risk group can be further sub divided into a group of 442 patients (16.6% of whole trial) with undetectable MRD at EOI and good risk cytogenetics who have a 5yr EFS of 97.4% (5yr OS 99.5%). Conclusion: This excellent long term outcome for a third of all patients with childhood ALL, low risk MRD and good risk cytogenetics in a large multi-center randomized controlled trial supports exploration of further reduction of therapy in this group to reduce TRM. This strategy is further supported by the observation that the rate of TRM is now similar the relapse death rate in this group, coupled with the very high salvage rates for those patients who do relapse. The superior OS for patients with undetectable MRD and good risk cytogenetics further highlights the additive strength of MRD to accurately predict outcome in the low risk cytogenetic group. Disclosures No relevant conflicts of interest to declare.

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Practical Applications of Oasis or Mirage: Assessing Low-Risk Investing from a Global Perspective

Practical Applications ◽

10.3905/pa.6.3.309 ◽

2019 ◽

Keyword(s):

Low Risk ◽

Global Perspective ◽

Practical Applications

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“Good Risk”: low-risk patients with ductal carcinoma in situ (DCIS) benefit from whole breast radiotherapy after breast conservation surgery (BCS)–long-term follow-up.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e12062 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e12062-e12062

Author(s):

Anna Niwinska ◽

Jacek Galecki ◽

Agnieszka Irena Jagiello-Gruszfeld ◽

Wojciech Michalski

Keyword(s):

Recurrence Rate ◽

Breast Conservation ◽

Low Risk ◽

Competing Risk ◽

Cancer Center ◽

Risk Of Recurrence ◽

Whole Breast Radiotherapy ◽

Risk Patients ◽

Good Risk

e12062 Background: Identification of patients group with low risk DCIS that do not require radiation therapy after BCS is still a challenge. We assessed recurrence rates in patients with „good risk” DCIS with and without radiotherapy after BCS, and subsequently compared our results with the long-term data from RTOG 9804 trial [1]. Methods: Out of 737 patients with DCIS managed between 1996-2011 at the Cancer Center Warsaw, Poland, 400 were treated conservatively. Out of those 133 were classified as „good risk” patients in accordance with RTOG 9804 trial criteria (DCIS < 2.5 cm, mammographically detected, NG1/G2 with margin = > 3 mm). 79 patients received only BCS and another 54 patients were treated with BCS and radiotherapy. Competing risk of recurrence, DFS and OS were calculated for both groups. The results were compared with the long-term observation results of RTOG 9804 trial. Results: The competing risk of recurrence after 10 years in the group treated with BCS and in patients receiving BCS with radiotherapy was 26% and 6% respectively (p = 0.013). 10-year DFS was 58% and 88% (p = 0.02) and OS was 94% and 97% (p = 0.3) respectively. Based on the ASTRO Conference 2018, 10-year recurrence risk without and with radiotherapy in RTOG 9804 trial were 9.1% and 1.7% [1]. In our study in comparison to RTOG 9804 trial results, more patients had DCIS sized 1.1-2.5 cm, excision margins of 3-9 mm and no patient received adjuvant tamoxifen. Conclusions: Similarly to the results of RTOG 9804 trial [1], radiotherapy reduced recurrence rate in “good risk” DCIS, however, in our study the recurrence rate was higher - probably due to difference in risk factors and no tamoxifen use. 1.McCormick B et al. Randomized trial evaluating radiation following surgical excision for “Good Risk” DCIS: 12year report from NRG/RTOG 9804. ASTRO October 21, 2018.

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Bleomycin: low-risk therapy for good-risk testicular cancer

Reactions Weekly ◽

10.1007/s40278-018-51560-6 ◽

2018 ◽

Vol 1719 (1) ◽

pp. 5-5

Keyword(s):

Testicular Cancer ◽

Low Risk ◽

Good Risk

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Identification of Genes Whose Expression Overlaps Age Boundaries and Correlates with Risk Groups in Paediatric and Adult Acute Myeloid Leukaemia

Cancers ◽

10.3390/cancers12102769 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2769

Author(s):

Lindsay Davis ◽

Ken I. Mills ◽

Kim H. Orchard ◽

Barbara-Ann Guinn

Keyword(s):

Gene Expression ◽

Acute Myeloid Leukaemia ◽

Myeloid Leukaemia ◽

Low Risk ◽

The Cancer Genome Atlas ◽

Sequencing Data ◽

Expression Levels ◽

Patient Subgroups ◽

Good Risk ◽

Acute Myeloid

Few studies have compared gene expression in paediatric and adult acute myeloid leukaemia (AML). In this study, we have analysed mRNA-sequencing data from two publicly accessible databases: (1) National Cancer Institute’s Therapeutically Applicable Research to Generate Effective Treatments (NCI-TARGET), examining paediatric patients, and (2) The Cancer Genome Atlas (TCGA), examining adult patients with AML. With a particular focus on 144 known tumour antigens, we identified STEAP1, SAGE1, MORC4, SLC34A2 and CEACAM3 as significantly different in their expression between standard and low risk paediatric AML patient subgroups, as well as between poor and good, and intermediate and good risk adult AML patient subgroups. We found significant differences in event-free survival (EFS) in paediatric AML patients, when comparing standard and low risk subgroups, and quartile expression levels of BIRC5, MAGEF1, MELTF, STEAP1 and VGLL4. We found significant differences in EFS in adult AML patients when comparing intermediate and good, and poor and good risk adult AML patient subgroups and quartile expression levels of MORC4 and SAGE1, respectively. When examining Kyoto Encyclopedia of Genes and Genomes (KEGG) (2016) pathway data, we found that genes altered in AML were involved in key processes such as the evasion of apoptosis (BIRC5, WNT1) or the control of cell proliferation (SSX2IP, AML1-ETO). For the first time we have compared gene expression in paediatric AML patients with that of adult AML patients. This study provides unique insights into the differences and similarities in the gene expression that underlies AML, the genes that are significantly differently expressed between risk subgroups, and provides new insights into the molecular pathways involved in AML pathogenesis.

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Practical Applications of International Low-Risk Investing

Practical Applications ◽

10.3905/pa.2015.3.1.114 ◽

2015 ◽

Vol 3 (1) ◽

pp. 1.10-4

Author(s):

Gauri Goyal

Keyword(s):

Low Risk ◽

Practical Applications

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Prognosis in Multiple Myeloma (MM): Characterization of “Losers” (L) in Good Risk and “Winners” (W) in High Risk Disease.

Blood ◽

10.1182/blood.v106.11.1161.1161 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1161-1161

Author(s):

Elias Anaissie ◽

Erik Rasmussen ◽

John Shaughnessy ◽

Guido Tricot ◽

Bart Barlogie

Keyword(s):

High Risk ◽

Serum Albumin ◽

Primary Treatment ◽

Low Risk ◽

Platelet Counts ◽

High Risk Disease ◽

Risk Patients ◽

Total Therapy ◽

Therapy Protocol ◽

Good Risk

Abstract Background: The clinical course of patients with MM is highly variable and, among currently available standard features, the presence of metaphase cytogenetic abnormalities (CA) is the parameter with the single best discriminatory power. The aim of this investigation was to determine, among the 1/3 high-risk patients with CA the W and among the remaining low-risk patients the L. Patients and Methods: We evaluated the baseline characteristics of > 2500 patients who received at least 1 high-dose melphalan-based autotransplant (AT). Poor risk was defined as pre-AT CA (within 90 days) while good risk was defined as no pre-TX1 CA. Poor outcome was death within 2 years of AT while good outcome was survival for ≥ 5 years. Four groups were identified: 403 patients without CA and >5yr survival (noCA/W), 288 without CA and <2yr survival (noCA/L), 122 with CA surviving >5yr (CA/W) and 350 with CA surviving <2yr (CA/L). Results: Among both CA and no CA groups, univariately significant pre-AT differentiating features between W vs L were serum albumin > 3mg/dL, b2M<3 mg/dL, CRP<6 mg/dL, hemoglobin > 10 mg/dL and platelet counts > 100/μL, LDH < 190 mg/dL, age < 65, female gender and primary treatment on Total Therapy protocol. By multivariate analysis, independently highly significant pre-AT factors that distinguished the 5 yr survivors from the early death (<2 years) patients included primary treatment on Total Therapy protocol, serum albumin > 3mg/dL, hemoglobin > 10 mg/dL, B2M<3 mg/dL, platelet counts >100/μL and CRP<6 mg/dL. These independent prognostic factors were almost identical for CA and noCA patients except for Hgb which was slightly more important than albumin in the CA population. Conclusion: Among MM patients receiving AT, treatment on Total Therapy protocol, higher Pre-AT albumin, hemoglobin and platelet count and lower b2M and CRP confer a survival advantage regardless of cytogenetic status (CA or noCA) and distinguish the W among the high-risk disease from the L among the low-risk patients.

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Ion Beam Induced Interfacial Reactions in Molybdenum Thin Films on Silicon

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100097466 ◽

1981 ◽

Vol 39 ◽

pp. 162-163

Author(s):

L. J. Chen ◽

L. S. Hung ◽

J. W. Mayer

Keyword(s):

Ion Beam ◽

Chemical Vapor ◽

Interfacial Reactions ◽

Practical Applications ◽

Microelectronic Devices ◽

Recent Emergence ◽

Chemical Vapor Deposited ◽

Atomic Mixing ◽

Silicon Interface ◽

Kinetics Of

When an energetic ion penetrates through an interface between a thin film (of species A) and a substrate (of species B), ion induced atomic mixing may result in an intermixed region (which contains A and B) near the interface. Most ion beam mixing experiments have been directed toward metal-silicon systems, silicide phases are generally obtained, and they are the same as those formed by thermal treatment.Recent emergence of silicide compound as contact material in silicon microelectronic devices is mainly due to the superiority of the silicide-silicon interface in terms of uniformity and thermal stability. It is of great interest to understand the kinetics of the interfacial reactions to provide insights into the nature of ion beam-solid interactions as well as to explore its practical applications in device technology.About 500 Å thick molybdenum was chemical vapor deposited in hydrogen ambient on (001) n-type silicon wafer with substrate temperature maintained at 650-700°C. Samples were supplied by D. M. Brown of General Electric Research & Development Laboratory, Schenectady, NY.

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1250-kilovolt scanning transmission electron microscope

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100113007 ◽

1984 ◽

Vol 42 ◽

pp. 624-625

Author(s):

T. Imura ◽

S. Maruse ◽

K. Mihama ◽

M. Iseki ◽

M. Hibino ◽

...

Keyword(s):

High Voltage ◽

Electron Probe ◽

Scanning Transmission Electron Microscope ◽

Pressure Vessels ◽

Practical Applications ◽

Voltage Generator ◽

Transmission Electron ◽

Scanning Transmission ◽

New Applications ◽

High Voltage Generator

Ultra high voltage STEM has many inherent technical advantages over CTEM. These advantages include better signal detectability and signal processing capability. It is hoped that it will explore some new applications which were previously not possible. Conventional STEM (including CTEM with STEM attachment), however, has been unable to provide these inherent advantages due to insufficient performance and engineering problems. Recently we have developed a new 1250 kV STEM and completed installation at Nagoya University in Japan. It has been designed to break through conventional engineering limitations and bring about theoretical advantage in practical applications.In the design of this instrument, we exercised maximum care in providing a stable electron probe. A high voltage generator and an accelerator are housed in two separate pressure vessels and they are connected with a high voltage resistor cable.(Fig. 1) This design minimized induction generated from the high voltage generator, which is a high frequency Cockcroft-Walton type, being transmitted to the electron probe.

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