BIOM-11. ENZYMATIC ASSAY USED TO MONITOR CHANGES IN ONCO-METABOLITE, D2HG, IN RESPONSE TO THERAPY

Abstract INTRODUCTION Gliomas are the most common and deadly adult brain cancers with a median survival time of less than 18 months. Many therapeutics have failed translating into effective therapies due to incomplete understanding of the disease and heterogeneity of tumors between patients. There is a need for methods that allow for continual access and analysis of glioma biomarkers. We sought to establish a reliable method for quantifying the onco-metabolite, D2HG. After optimizing this method, we used microdialysate and microperfusate to test our hypothesis that analysis of D2HG in response to therapy can indicate therapeutic efficacy sooner than current methods permit. METHODS Microdialysate and microperfusate were collected from the tumor centers and lateral ventricles of athymic nude mice implanted with IDH1 mutant PDX line GBM196. We performed microdialysis and microperfusion on consecutive days to determine baseline D2HG concentration. Following a five day period of TMZ treatment, we collected another round of microdialysis and microperfusion one week after treatment and again two weeks after treatment. We then used our optimized D2HG enzymatic assay to quantify the changes in D2HG in response to therapy. RESULTS Using our enzymatic D2HG assay, we were able to quantify D2HG as low as 30nM (30fmol/uL). We found a ~20% decrease in D2HG concentration in the tumor center and right lateral ventricle after 1 week of TMZ treatment (n=2), and ~36% decrease after 2 weeks of TMZ treatment (n=2). CONCLUSION Using a D2HG quantification assay to monitor changes in concentration of D2HG in microdialysate/microperfusate can predict sensitivity to therapy.

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T/NK “Nasal Type” Lymphomas: An Italian Cooperative Retrospective Survey.

Blood ◽

10.1182/blood.v104.11.4578.4578 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4578-4578

Author(s):

Livio Pagano ◽

Andrea Gallamini ◽

Giulio Trapè ◽

Daniele Mattei ◽

Eros Di Bona ◽

...

Keyword(s):

Survival Time ◽

Median Survival ◽

Nasal Obstruction ◽

Median Survival Time ◽

Bone Pain ◽

Skin Lesions ◽

Response To Therapy ◽

Italian Population ◽

Retrospective Survey ◽

Nasal Type

Abstract T/NK “nasal type” lymphoma is a neoplasm that shows a peculiar geographical distribution. In fact most of the reported cases come from Far Eastern countries such as Hong Kong, and Central America, particularly from Mexico; this kind of lymphoma occurrs rarely in western countries. Between 1997 and 2004, 19 new cases of T/NK nasal type lymphoma were diagnosed in 7 Italian Hematology Division. Patients characteristics were as follows: all caucasian; 14 men and 5 women; median age 53 years (range 20–80). The presentation at the onset was in the nasal cavity or adjacent structures in 15 cases, who presented symptoms like nasal obstruction, dysphagia, orbital edema; in 2 cases, skin lesions were the first sign of disease, followed by oropharingeal involvement; in 1 case, the patient was studied because of migrating bone pain, and in the last patient lymphoma presented as a right leg tumor. Considering the stage of disease, 10 patients presented a I stage (in 8 cases IA, 1 IB, and 1 IE); 3 patients were in stage II (2 IIB, 1 IIE); 6 patients presented an advanced stage disease (3 IVA, 3 IVB). Thus, early stage patients were 13, while advanced stages were 6. The median time from the onset of signs, as skin lesions, or symptoms, as nasal obstruction to diagnosis was 3 months, ranging between 1 and 24. Diagnosis was based on the finding of a T/NK phenotype by the histological examination of oropharingeal or cutaneous lesions in 17 cases, bioptical examination of the leg tumor in another patient, and by a bone marrow biopsy in the patient who presented bone pain. All patients were treated with chemotherapy alone (8 cases), or associated to radiotherapy (10 cases); 1 patient underwent chemotherapy, radiotherapy, and surgery. Chemotherapy regimens usually adopted contained anthracyclines (11 cases); in the other cases patients were treated with CVP (2 cases), low dosages of cyclophosphamide (1), cyclophosphamide-vinblastine-mithoxantrone-bleomicine (1), DHAP (3). Radiation dosages ranged between 27.5 and 47.5 Gy, with a median dosage of 40 Gy. Eight patients reached a clinical improvement, while 11 patients resulted refractory or presented a limited response to therapy The overall median survival time was 5 months (range from 1 to 48): Eleven patients died within 14 months from diagnosis, and the median survival time of this group was 6 months. At last follow-up (June 2004) 8 patients are still alive, with a time from diagnosis ranging beteween 2 and 48 months. The preliminary results of this retrospective survey confirmed that T/NK nasal type lymphoma is a very rare lymphoma in italian population, and it is characterized by a very bad prognosis. The rarity of this disease cause a lacking of a standardized therapeutic approaches. More data are needed to know the epidemiology of this kind of lymphoma in Europe.

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Confidence Bands for the Median Survival Time as a Function of the Covariates in the Cox Model

10.21236/ada237626 ◽

1991 ◽

Author(s):

Deborah Burr ◽

Hani Doss

Keyword(s):

Survival Time ◽

Median Survival ◽

Median Survival Time ◽

Cox Model ◽

Confidence Bands

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CTNI-30. THERAPEUTIC EFFECTS OF RADIOTHERAPY WITH CONCOMITANT AND ADJUVANT TEMOZOLOMIDE VERSUS RADIOTHERAPY WITH CONCOMITANT TEMOZOLOMIDE ALONE IN CHILDREN WITH DIPG: A SINGLE-CENTER EXPERIENCE WITH 82 CASES

Neuro-Oncology ◽

10.1093/neuonc/noaa215.197 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii49-ii49

Author(s):

Mingyao Lai ◽

Juan Li ◽

Qingjun Hu ◽

Jiangfen Zhou ◽

Shaoqun Li ◽

...

Keyword(s):

Survival Time ◽

Median Survival ◽

Median Survival Time ◽

Disease Recurrence ◽

Diffuse Intrinsic Pontine Glioma ◽

Hematological Toxicity ◽

Therapeutic Effects ◽

Single Center Experience ◽

Adjuvant Temozolomide ◽

Temozolomide Chemotherapy

Abstract OBJECTIVE To retrospectively analyze the therapeutic effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy with concomitant temozolomide alone for pediatric diffuse intrinsic pontine glioma (DIPG), and to evaluate the value of temozolomide in the treatment of pediatric DIPG. METHODS The clinical data of children with confirmed DIPG in Guangdong Sanjiu Brain Hospital between January 1, 2010 and December 30, 2019 were collected. The inclusive criteria included (1) receiving a total radiotherapy dose of 54 Gy in 27 fractions, (2) treated with concomitant temozolomide chemotherapy, and (3) with or without adjuvant temozolomide chemotherapy. RESULTS A total of 82 pediatric patients were eligible for the study, with a median age of 7 years (range 2–16 years). The median follow-up was 8.6 months (range 2–28 months) and the median survival time was 9.4 months. The median survival time of 66 patients treated with radiotherapy with concomitant and adjuvant temozolomide was 9.8 months, longer than 7.5 months of the other 16 patients treated with radiotherapy with concomitant temozolomide alone, with statistical differences (P=0.010). Moreover, bevacizumab and nimotuzumab didn’t bring survival benefits to patients with disease recurrence or progression. Hematological toxicity (Grade IV) was not found. CONCLUSION Radiotherapy with concomitant and adjuvant temozolomide prolongs the survival time of children with DIPG.

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Survival after surgery among patients with cholangiocarcinoma in Northeast Thailand according to anatomical and morphological classification

BMC Cancer ◽

10.1186/s12885-021-08247-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chaiwat Tawarungruang ◽

Narong Khuntikeo ◽

Nittaya Chamadol ◽

Vallop Laopaiboon ◽

Jaruwan Thuanman ◽

...

Keyword(s):

Survival Rate ◽

Survival Time ◽

Median Survival ◽

Median Survival Time ◽

Cox Regression ◽

Survival Rates ◽

Care Program ◽

Tumor Location ◽

Northeast Thailand ◽

Curative Surgery

Abstract Background Cholangiocarcinoma (CCA) has been categorized based on tumor location as intrahepatic (ICCA), perihilar (PCCA) or distal (DCCA), and based on the morphology of the tumor of the bile duct as mass forming (MF), periductal infiltrating (PI) or intraductal (ID). To date, there is limited evidence available regarding the survival of CCA among these different anatomical and morphological classifications. This study aimed to evaluate the survival rate and median survival time after curative surgery among CCA patients according to their anatomical and morphological classifications, and to determine the association between these classifications and survival. Methods This study included CCA patients who underwent curative surgery from the Cholangiocarcinoma Screening and Care Program (CASCAP), Northeast Thailand. The anatomical and morphological classifications were based on pathological findings after surgery. Survival rates of CCA and median survival time since the date of CCA surgery and 95% confidence intervals (CI) were calculated. Multiple cox regression was performed to evaluate factors associated with survival which were quantified by hazard ratios (HR) and their 95% CIs. Results Of the 746 CCA patients, 514 had died at the completion of the study which constituted 15,643.6 person-months of data recordings. The incidence rate was 3.3 per 100 patients per month (95% CI: 3.0–3.6), with median survival time of 17.8 months (95% CI: 15.4–20.2), and 5-year survival rate of 24.6% (95% CI: 20.7–28.6). The longest median survival time was 21.8 months (95% CI: 16.3–27.3) while the highest 5-year survival rate of 34.8% (95% CI: 23.8–46.0) occurred in the DCCA group. A combination of anatomical and morphological classifications, PCCA+ID, was associated with the longest median survival time of 40.5 months (95% CI: 17.9–63.0) and the highest 5-year survival rate of 42.6% (95% CI: 25.4–58.9). The ICCA+MF combination was associated with survival (adjusted HR: 1.45; 95% CI: 1.01–2.09; P = 0.013) compared to ICCA+ID patients. Conclusions Among patients receiving surgical treatment, those with PCCA+ID had the highest 5-year survival rate, which was higher than in groups classified by only anatomical characteristics. Additionally, the patients with ICCA+MF tended to have unfavorable surgical outcomes. Showed the highest survival association. Therefore, further investigations into CCA imaging should focus on patients with a combination of anatomical and morphological classifications.

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Culex quinquefasciatus (Diptera: Culicidae) survivorship following the ingestion of bird blood infected with Haemoproteus sp. parasites

Parasitology Research ◽

10.1007/s00436-021-07196-7 ◽

2021 ◽

Author(s):

Dayvion R. Adams ◽

Andrew J. Golnar ◽

Sarah A. Hamer ◽

Michel A. Slotman ◽

Gabriel L. Hamer

Keyword(s):

Survival Time ◽

Median Survival ◽

Culex Quinquefasciatus ◽

Median Survival Time ◽

Bird Species ◽

Protozoan Parasite ◽

Cardinalis Cardinalis ◽

Vector Borne ◽

And Behavior ◽

Negative Controls

AbstractArthropod vectors are frequently exposed to a diverse assemblage of parasites, but the consequence of these infections on their biology and behavior are poorly understood. We experimentally evaluated whether the ingestion of a common protozoan parasite of avian hosts (Haemoproteus spp.; Haemosporida: Haemoproteidae) impacted the survivorship of Culex quinquefasciatus (Say) (Diptera: Culicidae). Blood was collected from wild northern cardinals (Cardinalis cardinalis) in College Station, Texas, and screened for the presence of Haemoproteus spp. parasites using microscopic and molecular methods. Experimental groups of Cx. quinquefasciatus mosquitoes were offered Haemoproteus-positive cardinal blood through an artificial feeding apparatus, while control groups received Haemoproteus-negative cardinal blood or domestic canary (Serinus canaria domestica) blood. Culex quinquefasciatus mosquitoes exposed to Haemoproteus infected cardinal blood survived significantly fewer days than mosquitoes that ingested Haemoproteus-negative cardinal blood. The survival of mosquitoes fed on positive cardinal blood had a median survival time of 18 days post-exposure and the survival of mosquitoes fed on negative cardinal blood exceeded 50% across the 30 day observation period. Additionally, mosquitoes that fed on canary controls survived significantly fewer days than cardinal negative controls, with canary control mosquitoes having a median survival time of 17 days. This study further supports prior observations that Haemoproteus parasites can be pathogenic to bird-biting mosquitoes, and suggests that Haemoproteus parasites may indirectly suppress the transmission of co-circulating vector-borne pathogens by modulating vector survivorship. Our results also suggest that even in the absence of parasite infection, bloodmeals from different bird species can influence mosquito survivorship.

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3217 Catatonia, Delirium and Coma: Implications for Mortality

Journal of Clinical and Translational Science ◽

10.1017/cts.2019.91 ◽

2019 ◽

Vol 3 (s1) ◽

pp. 37-37

Author(s):

Jo Ellen Wilson ◽

Sarasota Mihalko ◽

Stephan Heckers ◽

Pratik P. Pandharipande ◽

Timothy D. Girard ◽

...

Keyword(s):

Survival Time ◽

Critically Ill ◽

Median Survival ◽

Critically Ill Patients ◽

Median Survival Time ◽

Rating Scale ◽

Brain Dysfunction ◽

Survival Times ◽

Dsm 5 ◽

Acute Brain Dysfunction

OBJECTIVES/SPECIFIC AIMS: Delirium, a form of acute brain dysfunction, characterized by changes in attention and alertness, is a known independent predictor of mortality in the Intensive Care Unit (ICU). We sought to understand whether catatonia, a more recently recognized form of acute brain dysfunction, is associated with increased 30-day mortality in critically ill older adults. METHODS/STUDY POPULATION: We prospectively enrolled critically ill patients at a single institution who were on a ventilator or in shock and evaluated them daily for delirium using the Confusion Assessment for the ICU and for catatonia using the Bush Francis Catatonia Rating Scale. Coma, was defined as a Richmond Agitation Scale score of −4 or −5. We used the Cox Proportional Hazards model predicting 30-day mortality after adjusting for delirium, coma and catatonia status. RESULTS/ANTICIPATED RESULTS: We enrolled 335 medical, surgical or trauma critically ill patients with 1103 matched delirium and catatonia assessments. Median age was 58 years (IQR: 48 - 67). Main indications for admission to the ICU included: airway disease or protection (32%; N=100) or sepsis and/or shock (25%; N=79. In the unadjusted analysis, regardless of the presence of catatonia, non-delirious individuals have the highest median survival times, while delirious patients have the lowest median survival time. Comparing the absence and presence of catatonia, the presence of catatonia worsens survival (Figure 1). In a time-dependent Cox model, comparing non-delirious individuals, holding catatonia status constant, delirious individuals have 1.72 times the hazards of death (IQR: 1.321, 2.231) while those with coma have 5.48 times the hazards of death (IQR: 4.298, 6.984). For DSM-5 catatonia scores, a 1-unit increase in the score is associated with 1.18 times the hazards of in-hospital mortality. Comparing two individuals with the same delirium status, an individual with a DSM-5 catatonia score of 0 (no catatonia) will have 1.178 times the hazard of death (IQR: 1.086, 1.278), while an individual with a score of 3 catatonia items (catatonia) present will have 1.63 times the hazard of death. DISCUSSION/SIGNIFICANCE OF IMPACT: Non-delirious individuals have the highest median survival times, while those who are comatose have the lowest median survival times after a critical illness, holding catatonia status constant. Comparing the absence and presence of catatonia, the presence of catatonia seems to worsen survival. Those individual who are both comatose and catatonic have the lowest median survival time.

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MEDIAN SURVIVAL TIME

The Lancet ◽

10.1016/s0140-6736(82)92134-1 ◽

1982 ◽

Vol 319 (8280) ◽

pp. 1076

Author(s):

P.M. Stell

Keyword(s):

Survival Time ◽

Median Survival ◽

Median Survival Time

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Repeated confidence intervals for the median survival time

Biometrika ◽

10.1093/biomet/72.3.619 ◽

1985 ◽

Vol 72 (3) ◽

pp. 619-625 ◽

Cited By ~ 37

Author(s):

CHRISTOPHER JENNISON ◽

BRUCE W. TURNBULL

Keyword(s):

Survival Time ◽

Confidence Intervals ◽

Median Survival ◽

Median Survival Time

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Phase II study with the combination etoposide, doxorubicin, and cisplatin in advanced measurable gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1989.7.9.1310 ◽

1989 ◽

Vol 7 (9) ◽

pp. 1310-1317 ◽

Cited By ~ 211

Author(s):

P Preusser ◽

H Wilke ◽

W Achterrath ◽

U Fink ◽

L Lenaz ◽

...

Keyword(s):

Survival Time ◽

Median Survival ◽

Phase Ii ◽

Metastatic Disease ◽

Median Survival Time ◽

Response Rate ◽

Response Duration ◽

World Health ◽

Who Grade ◽

Median Response

In this phase II multicenter trial, 67 evaluable patients with advanced measurable gastric carcinoma were treated with a combination of etoposide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (EAP). The overall response rate was 64%, including 21% complete responses (CRs). In 55 patients with metastatic disease, 31 responses (51%) including eight CRs (15%) were achieved. Responses were seen in all metastatic sites, but the response rate was lower in patients with peritoneal carcinomatosis. In 12 patients with locoregional disease, six CRs and six partial responses (PRs) were observed. Eight CRs (three and five in patients with metastatic and locoregional disease, respectively) were pathologically confirmed. The overall median response duration was 7 months; it was 16 months for patients achieving CR (22 months for pathologically confirmed CR [pCR]), and 6 months for PR. The median survival time for all patients was 9 months, for the patients who achieved CR 17 months, for pCR 23 months, and for PR 9.5 months. Median survival time for all patients with metastatic disease was 8 months, and for locoregional disease 12.5 months. Six patients (9%) (four local, two metastatic disease) were alive at 2 years, and four patients are alive and disease free at 35+ to 56+ months. Main toxicities were leukopenia and thrombocytopenia, with 64% of patients developing grade 3 to 4 myelosuppression and 12% severe infections. Nonhematologic toxicities of World Health Organization (WHO) grade 4 were not observed.

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