Management of renal masses in an octogenarian cohort: Is there a right approach?

497 Background: Although several guidelines outline management options for patients with renal masses, few studies describe treatment strategies and outcomes in octogenarians. We sought to review outcomes in this population managed with active surveillance (AS), partial nephrectomy (PN), or radical nephrectomy (RN). Methods: Data were collected on 113 octogenarian patients referred for management of renal masses at Moffitt Cancer Center between 2000 and 2013. Patients were treated with AS, PN, or RN. Univariate and multivariable Cox regression models measured association of management modality and survival. Kaplan-Meier survival analysis was used for overall survival and log-rank tests were used to compare survival curves. Covariates include age, Eastern Cooperative Oncology Group (ECOG) score, clinical and pathologic stage, tumor size, creatinine, creatinine clearance, and overall survival. Results: Out of 113 patients, 27 (22%) underwent AS, 33 (26.8%) underwent PN, and 53 (43%) underwent RN. The mean age was 83 years (range, 80-92). AS patients had a higher mean age (84 years) than PN patients (81.9 years), but not with RN patients (83 years) (p=0.008). At a median follow-up of 30.6 months (IQR 9.9-56), 13 (48%), 10 (30.3%), and 29 (54.7%) patients died from any cause in AS, PN, and RN patients respectively. PN patients tended to have a longer median overall survival at 81 months versus 55.8 and 57 months for AS and RN respectively, but this did not reach statistical significance on univariate (p=0.588) or multivariate analysis (p=0.29). On subgroup analysis of cT1a patients, there was also no difference in overall survival among treatment arms on univariate (p=0.654) and multivariate analysis (p=0.47). At 1 year follow-up, there was no difference in creatinine levels between treatment arms (p=0.331). However, mean creatinine clearance was lower in RN patients (35.8 ml/min) compared to AS (50.7 ml/min) and PN (48.1 ml/min) (p=0.024). Conclusions: Active treatment with PN and RN may not provide a survival advantage among octogenarians. Renal function was inferior in RN patients but comparable between AS and PN patients at 1 year follow-up.

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HER2-low and gastric cancer: A prognostic biomarker?

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16086 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16086-e16086

Author(s):

Bruno Cezar de Mendonça Uchôa ◽

Rafaela Pirolli ◽

Luciana Beatriz Mendes Gomes Siqueira ◽

Francisca Giselle Rocha Moura ◽

Ana Paula Rondina Correa ◽

...

Keyword(s):

Gastric Cancer ◽

Multivariate Analysis ◽

Prognostic Value ◽

Cox Regression ◽

Prognostic Biomarker ◽

Statistical Significance ◽

Gastroesophageal Junction ◽

Rank Test ◽

Cancer Center ◽

First Line

e16086 Background: The role of HER2 positive (HER2+) as a prognostic biomarker for gastric/gastroesophageal junction cancer (G-GEJC) is controversial. Recently, the HER2-low (HER2l) concept has emerged and proved to predict response to trastuzumab deruxtecan in metastatic scenario. Data on HER2l prognostic value are missing. Methods: All consecutive patients with metastatic G-GEJC, tested for HER2 in the primary tumor or in the metastatic tissue before initiating first-line therapy at A.C. Camargo Cancer Center, were retrospectively recruited. The primary objective was to compare the overall survival (OS: from the metastasis diagnosis to death by any cause) between HER2l and HER2 negative (HER2-) populations. Secondarily, we aimed to compare the first-line progression-free survival (PFS) between HER2l and HER2-, to analyze prognostic factors associated with OS and to compare the OS between HER2+ and HER2l/HER2-. The HER2 immunohistochemistry (IHC) tests were performed with the Ventana anti-HER2/neu kit, by specialized gastrointestinal pathologists of the study center, using the AJCC HER2 scoring criteria for gastric cancer. In situ hybridization (ISH) was done when IHC 2+ was detected. HER2+ were IHC 3+ or 2+ amplified by ISH; HER2l, 1+ or 2+ non-amplified; HER-, 0+. Kaplan-Meier curves, Log-Rank test and Cox regression were used for survival analysis. Cox regression was used for uni and multivariate analysis. Results: From June, 2008 to July, 2020, 398 patients were included (48 HER2+; 103 HER2l; 247 HER2-). The median follow-up was 31 months (m). Median age at diagnosis was 58 years; the majority were men (62.8%), caucasian (50.8%), with gastric (81% vs 19% GEJ), diffuse (50.3%), de novo metastatic (57.0%) tumors. In comparison to HER2l/HER2-, HER2+ group had superior rates of men, GEJC, intestinal subtype and non-visceral metastasis. Central nervous system metastases were uncommon, and proportionally higher in HER2+ tumors (HER2+: 6.2%; HER2l: 2.9%; HER2-: 2.0%; p = 0.27). There were no imbalances between HER2l and HER2- groups. The median OS was similar for HER2l and HER2- (13m for both; HR 1.0, 95%CI 0.76-1.31; p = 1.0), as it was the PFS (5m for both; HR 0.84, 95%CI 0.65-1.08; p = 0.18). These results did not vary on dependence of IHC + (0 vs 1 + vs 2+). HER2+ tumors had a superior median OS (17m vs 13m for HER2l/HER2-; HR 0.70, 95%CI 0.49-0.99; p = 0.046). When ungrouping HER2l/HER2-, this numerical difference remains, with a loss of statistical significance (17m vs 13m vs 13m; HR 0.87, 95%CI 0.74-1.02; p = 0.12). HER2+, > 1 line of treatment and metastasectomy were predictive for improved OS in multivariate analysis. HER2l was neither predictive for OS nor PFS. Conclusions: Although HER2-low emerged as a new predictive biomarker in metastatic gastric cancer, its prognostic value could not be proved in this study, with an absence of impact in OS. HER2+, however, was associated with improved survival.

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Prognostic Factors for Myelodysplastic Syndrome in the Veteran Population: Single Institution Experience.

Blood ◽

10.1182/blood.v110.11.4622.4622 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4622-4622

Author(s):

Michael Axelson ◽

Shirisha Reddy ◽

Crystal Lumby ◽

Sue Sivess-Franks ◽

Jonathan Dowell ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Blood Transfusion ◽

Cox Regression ◽

Medical Center ◽

Univariate Analysis ◽

Single Institution ◽

Number Of Patients

Abstract Background: Myelodyplastic syndrome (MDS) is the disease of the elderly and increasingly common in the veteran population. Here we report a single institution experience with MDS at the Dallas VA Medical Center. Patients and Method: From a period of 1998–2007, eighty three pts were identified out of which 54 pts had bone marrow (BM) biopsy proven diagnosis of MDS. Overall survival (OS) analysis with dependent variables (Age at diagnosis, IPSS Score, WHO morphologic diagnosis, number of blood and platelet transfusions required, Hb level, ANC, cytogenetics, blast percentage, BM cellularity at diagnosis) were conducted by selection method “foreward” and only these significant variables were used in the Cox regression for multivariate analysis. Methods of Kaplan and Meier were used to generate OS curves. Results: The median age of diagnosis was 74 yrs with a median follow up time of 12.5 months. The WHO morphologic subtype was RA/RARS (n=13), Del5q (n=1), RCMD/RCMDRS (n=34), RAEB1 (n=3), RAEB2 (n=1), missing (n=2). The distribution of IPSS score was 0 (n=25); 0.5 (n=15); 1.0 (n=8), 1.5 (n=4), missing (n=2). Five pts had treatment related MDS and 3 pts transformed to AML. One patient had concurrent MGUS and one patient developed multiple myeloma. At diagnosis, 23 pts had a hemoglobin (Hb) value of less than 10g/dl. Only 4 pts had ANC less than 500; sixteen pts had ANC 500–1800 and 34 pts had normal counts. A majority of pts had normal cytogenetics (n=37), 5 pts had good risk, 5 pts had intermediate risk and 7 pts had poor risk cytogenetics. Six pts had hypocellular (<30%) BM at diagnosis whereas 16 pts had a hypercellular marrow (> 50%). Only 4 pts had more than 5% blast in the BM. Twenty nine pts eventually became blood transfusion dependent and 12 pts needed platelet transfusion at some point. Thirty six pts were treated with erythropoietin (with or without neupogen) and 13 pts received some type of disease modifying therapy (5-azacytidine/lenalidomide/ATG/clinical trial). The mean survival time was 106 months. Median survival was not reached at the time of analysis. In the univariate analysis, IPSS score (p=0.003), No. of blood transfusions (p=0.028), cytogenetics (p=0.0001) and blast percentage (p=0.0015), were statistically significant. BM cellularity (p=0.06) and Hb level (p=0.09) showed a trend towards significance. On multivariate analysis, Hb greater than 10 (HR 0.08; p=0.011), abnormal cytogenetics (HR 4.2; p=0.001), BM Blast > 5% (p=0.026) and BM cellularity < 30% (HR 4.6; p=0.033) emerged as the significant predictors of overall survival. IPSS score or Blood transfusion requirement did not pan out to be significant. Conclusion: MDS in the veteran population may be different from general population and may have unique predictors of survival. A larger number of patients and longer duration of follow up is required to further evaluate these prognostic factors.

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Prognostic implication of p53 mutations in HNSCC: Results of Intragroup margin study (E4393)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.5504 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 5504-5504

Author(s):

L. M. Poeta ◽

M. A. Goldwasser ◽

A. Forastiere ◽

N. Benoit ◽

J. Califano ◽

...

Keyword(s):

Overall Survival ◽

Cox Regression ◽

Eastern Cooperative Oncology Group ◽

P53 Mutation ◽

Rank Test ◽

Curative Intent ◽

Cox Regression Analysis ◽

Linear Effect ◽

Genetic Status

5504 Background: The role of p53 as a prognostic marker in head and neck squamous cell carcinoma (HNSCC) is controversial. The intent of this study was to evaluate rigorously the prognostic value of p53 genetic status. Methods: Tumor samples from 480 HNSCC patients treated surgically with curative intent were collected in a prospective multicenter study over 5 years. 57 cases were not analyzed due to technical or administrative factors. Mutation status was determined in the 423 remaining cases, using p53 chip (GP53 GeneChip from Affymetrix, Inc., Santa Clara, CA) which identifies mutations in exons 2 through 11. Indeterminate calls were investigated using Surveyor and/or DHPLC analysis and all mutations were confirmed with an automated fluorescent system or manual sequencing. Clinical follow-up was accomplished following Eastern Cooperative Oncology Group protocol. Results: Median follow-up of the 423 evaluable subjects was 5.4 years with all patients followed at least 3 years. Mutation of p53 gene was present in 224 (53%) cases. There we significantly fewer mutations in tumors arising in the oropharynx (chi-square p = 0.02). The presence of p53 mutation was significantly associated with decreased overall survival. Median survival for patients with tumors with p53 mutation was 3.1 years compared to 5.4 years fro WT tumors (HR = 1.4, 95% CI =1.1 to 1.8, p = 0.01 log-rank test). This proved to be independent of tumor site in multivariate analysis. When mutations were segregated according to their effect on biological function through alteration of key DNA binding domains a Cox regression analysis revealed a statistically significant linear effect of the more disruptive mutations on overall survival with a HR of 1.3 for comparison of each group to the one of lower risk (more vs. less disruptive mutation v. WT (p = 0.001 Wald test). Conclusions: This large prospective series shows a strong relationship between TP53 mutation and prognosis in HNSCC patients. Furthermore, the biological impact of specific mutations has a predictable graded relation to clinical outcome. The results set the stage for use of p53 genetic status in the design of future clinical trials and support the development of targeted therapy to restore wild-type p53 function. No significant financial relationships to disclose.

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Partial Cystectomy after Neoadjuvant Chemotherapy: Memorial Sloan Kettering Cancer Center Contemporary Experience

International Scholarly Research Notices ◽

10.1155/2014/702653 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Wassim M. Bazzi ◽

Ryan P. Kopp ◽

Timothy F. Donahue ◽

Melanie Bernstein ◽

Paul Russo ◽

...

Keyword(s):

Overall Survival ◽

Neoadjuvant Chemotherapy ◽

Cox Regression ◽

Surgical Margin ◽

Partial Cystectomy ◽

Intravesical Therapy ◽

Rank Test ◽

Cancer Center ◽

Positive Surgical Margin

Objective. To report our contemporary experience with partial cystectomy after neoadjuvant chemotherapy. Patients and Methods. Retrospective review of patients who underwent neoadjuvant chemotherapy and partial cystectomy for urothelial cell carcinoma of the bladder at Memorial Sloan Kettering Cancer Center from 1995 to 2013. Log-rank test and Cox regression models were used to analyze variables possibly associated with recurrence-free, advanced recurrence-free (free from recurrence beyond salvage with intravesical therapy or radical cystectomy), and overall survival. Results. All 36 patients had a solitary tumor <5 cm in size. Twenty-one patients (58%) achieved cT0 following neoadjuvant chemotherapy with 7 (33%) having residual disease at PC. At last follow-up, 19 (53%) patients had recurrence, 15 (42%) had advanced recurrence, 10 (28%) died of disease, and 22 (61%) maintained an intact bladder. Median follow-up of those who were with no evidence of disease was 17 months. On univariable analysis, after neoadjuvant chemotherapy positive nodes on imaging and positive surgical margin at partial cystectomy were both associated with worse recurrence-free, advanced recurrence-free, and overall survival. Five-year recurrence-free, advanced recurrence-free, and overall survival were 28%, 51%, and 63%, respectively. Conclusion. Partial cystectomy following neoadjuvant chemotherapy provides acceptable oncologic outcomes in highly selected patients with muscle-invasive bladder cancer.

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Survival Analysis of Additional Chromosomal Aberrations in Philadelphia Chromosome Positive and Negative Cells: A Single Institutional

Blood ◽

10.1182/blood.v118.21.2523.2523 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2523-2523

Author(s):

William Bulkeley ◽

Bijal D. Shah ◽

Monique A Hartley ◽

John M. Bennett ◽

Rami S. Komrokji ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Disease Progression ◽

Cox Regression ◽

Conflicts Of Interest ◽

Statistical Significance ◽

Philadelphia Chromosome ◽

Response To Therapy ◽

Blast Phase ◽

Clone Group

Abstract Abstract 2523 Background: Chronic myeloid leukemia (CML) is a clonal stem cell malignancy associated with the Philadelphia chromosome, t(9;22)(q34q31)/BCR-ABL gene fusion. Additional cytogenetic abnormalities have been known to emerge in Philadelphia (Ph) positive cells (additional Ph+ clones) or Ph negative cells (Ph- clones) at diagnosis, or during or post tyrosine kinase inhibitor (TKI) therapy. Many studies have elucidated that the presence of some Ph+ clones were frequently associated with disease progression, while presence of Ph- clones were unrelated to disease outcome. A majority of studies have shown a waxing and waning of Ph- clonality in response to therapy. However, there remains no solid data regarding overall survival comparing Ph+ and Ph- clones over a long term period. This study focuses on the observation of clonal evolution in various phases of CML, and the relationship to overall survival, disease resistance, kinase domain mutation (KDM) and progression to accelerated or blast phase in patients with CML. Materials and Methods: Data from 318 patients who were diagnosed with CML was retrieved from Moffitt Cancer Center during January 1990-December 2010. Patients are divided into three groups based on the presence of additional ph+ clone (A), ph- clone (B) and absence of both (C). Clinicopathologic results including initial diagnosis date, nature and frequency of clone, copy of clone at karyotyping, disease status in response to treatment and overall outcome were documented and statistically analyzed. All patients with Ph- and Ph+ clones have been treated with TKIs since 2001. Median overall survival and median disease progression survival were compared between conal ph- and clonal ph+ group by the log-rank test. Survival curves were generated using the Kaplan–Meier method. All reported P values are two-sided. Cox Regression (multivariate analysis) was also performed for time to progression. Results: Of 318 (average age 57, range: 19 to 89, M:F=1:1), 17 carried ph- clones (5.3%) and 41 showed additional ph+ clones (12.9%) and the rest (258) lacked additional ph+ or ph- clones. Additional clonal cytogenetic aberrations were random with the most frequent occurrence of trisomy 8 (7 of 17 ph- and 14 of 41 ph+ clones, respectively) and isochromosome 17q (4 in ph+ clone only). There is a higher rate of transformation to accelerated/blast phase in Ph+ additional clones (36.6%,15 of 41) as compared to Ph- additional clone (17.6%, 3 of 17) and Ph+ without additional clones(11.1%, 29 of 260) (p=0.015). The overall median survival is shorter in patients with ph+ clones (133.4 months) than in those with ph- clones (172 months) (p<0.005). KDM were observed in 27 of 110 tested patients (24.5%), and many of them fell into the Ph+ clone group (10 of 22 tested) and fewer into ph- clone group (3 of 10 tested) (p<0.005). Statistical analysis proved that there is a higher rate of transformation to accelerated/blast phase in the presence of a KDM (p<0.005). Of note, most of those with ph- clones had only one episode (59%) with 41% having more than one occurrence and lasting from 6–58 months (average 21.1 months), while in those 41 patients with Ph+ clone; a subset (18 of 41, 43.9%) showed a long-lasting ph+ clone over months (ranging from 2 months to 70 months, average 14.5 months) and the remaining only occurred one occasion (23 of 41, 56.1%). Multivariate analysis for disease progression demonstrated statistical significance with regards to both the ph+ clone and kinase mutation categories (p=0.003 and 0.034). Conclusion: Most Ph+ or Ph- clones are occasionally observed during the long course of CML, with a minor subset of clones showing persistency, especially in Ph- ones. The presence of an additional Ph+ clone is correlated with disease progression, drug resistance and shorter overall survival in comparison to a Ph- clone. A relatively long overall survival is observed in patients with ph- clones. Ph- clones were often identified during disease remission regardless of frequency of clonal copy or clonal persistence. The outcome of patients with concurrent Ph+ and Ph- clones was dictated by the Ph+ clone. Disclosures: No relevant conflicts of interest to declare.

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Impact of superselective intra-arterial and systemic chemoradiotherapy for gingival carcinoma; analysis of treatment outcomes and prognostic factors

10.21203/rs.3.rs-56332/v2 ◽

2020 ◽

Author(s):

Yuki Mukai ◽

Yuichiro Hayashi ◽

Izumi Koike ◽

Toshiyuki Koizumi ◽

Madoka Sugiura ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Clinical Stage ◽

Performance Status ◽

Univariate Analysis ◽

Stage Iv ◽

Progression Free Survival ◽

Late Toxicity ◽

Free Survival

Abstract Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC).　Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8%, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4%, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6%, 95% CI: 62.7–85.2; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2%, 95% CI: 64.2–86.4; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

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Incidence, Survival, and Associated Factors Estimation in Osteosarcoma Patients with Lung Metastasis: A Single-center Experience of 11 Years in Tianjin, China

10.21203/rs.3.rs-1071152/v1 ◽

2021 ◽

Author(s):

Chao Zhang ◽

Haixiao Wu ◽

Guijun Xu ◽

Wenjuan Ma ◽

Lisha Qi ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Regression Analysis ◽

Prognostic Factors ◽

Lung Metastasis ◽

Associated Factors ◽

Cox Regression ◽

Cancer Center ◽

Single Center ◽

Cox Regression Analysis

Abstract Background: Osteosarcoma is the most common primary malignant bone tumor. The current study was conducted to describe the general condition of patients with primary osteosarcoma in a single cancer center in Tianjin, China and to investigate the associated factors in osteosarcoma patients with lung metastasis. Methods: From February 2009 to October 2020, patients from Tianjin Medical University Cancer Institute and Hospital, China were retrospectively analyzed. The Kaplan–Meier method was used to evaluate the overall survival of osteosarcoma patients. Prognostic factors of patients with osteosarcoma were identified by the Cox proportional hazard regression analysis. Risk factor of lung metastasis in osteosarcoma were investigated by the logistic regression model. Results: A total of 203 patients were involved and 150 patients were successfully followed up for survival status. The 5-year survival rate of osteo-sarcoma patients was 70.0%. Surgery, bone and lung metastasis were the significant prognostic factors in multivariable Cox regression analysis. Twenty-one (10.3%) patients showed lung metastasis at the diagnosis of osteosarcoma and 67 (33%) lung metastases during the later course. T3 stage (OR=11.415, 95%CI 1.362-95.677, P=0.025) and synchronous bone metastasis (OR=6.437, 95%CI 1.69-24.51, P=0.006) were risk factors of synchronous lung metastasis occurrence. Good necrosis (≥90%, OR=0.097, 95%CI 0.028-0.332, P=0.000) and elevated Ki-67 (≥50%, OR=4.529, 95%CI 1.241-16.524, P=0.022) were proved to be significantly associated with metachronous lung metastasis occurrence. Conclusion: The overall survival, prognostic factors and risk factors for lung metastasis in this single center provided insight about osteosarcoma management.

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EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.4.1248 ◽

1998 ◽

Vol 16 (4) ◽

pp. 1248-1255 ◽

Cited By ~ 369

Author(s):

E de Alava ◽

A Kawai ◽

J H Healey ◽

I Fligman ◽

P A Meyers ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Molecular Heterogeneity ◽

Curative Intent ◽

Adequate Treatment ◽

Fusion Transcripts ◽

Fusion Type

PURPOSE More than 90% of Ewing's sarcomas (ES) contain a fusion of the EWS and FLI1 genes, due to the t(11;22)(q24;q12) translocation. At the molecular level, the EWS-FLI1 rearrangements show great diversity. Specifically, many different combinations of exons from EWS and FLI1 encode in-frame fusion transcripts and result in differences in the length and composition of the chimeric protein, which functions as an oncogenic aberrant transcription factor. In the most common fusion type (type 1), EWS exon 7 is linked in frame with exon 6 of FLI1. As the fundamental pathogenetic lesion in ES, the molecular heterogeneity of these fusion transcripts may have functional and clinical significance. PATIENTS AND METHODS We performed a clinical and pathologic analysis of 112 patients with ES in which EWS-FLI1 fusion transcripts were identified by reverse-transcriptase polymerase chain reaction (RT-PCR). Adequate treatment and follow-up data were available in 99 patients treated with curative intent. Median follow-up in these 99 patients was 26 months (range, 1 to 140 months). Univariate and multivariate survival analyses were performed that included other prognostic factors, such as age, tumor location, size, and stage. RESULTS Among the 99 patients suitable for survival analysis, the tumors in 64 patients contained the type 1 fusion and in 35 patients contained less common fusion types. Stage at presentation was localized in 74 patients and metastatic in 25. Metastases (relative risk [RR] = 2.6; P = .008), and type 1 EWS-FLI1 fusion (RR = 0.37; P = .014) were, respectively, independent negative and positive prognostic factors for overall survival by multivariate analysis. Among 74 patients with localized tumors, the type 1 EWS-FLI1 fusion was also a significant positive predictor of overall survival (RR = 0.32; P = .034) by multivariate analysis. CONCLUSION EWS-FLI1 fusion type appears to be prognostically relevant in ES, independent of tumor site, stage, and size. Further studies are needed to clarify the biologic basis of this phenomenon.

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Molecular annotation of extramedullary acute myeloid leukemia to identify prevalence of targetable mutations.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.7024 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 7024-7024

Author(s):

Somedeb Ball ◽

Todd C Knepper ◽

Yehuda Ethan Deutsch ◽

Chirag K Bhagat ◽

Justin M. Watts ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Multivariate Analysis ◽

Myeloid Leukemia ◽

Cox Regression ◽

Cancer Center ◽

Genomic Alteration ◽

Risk Category ◽

Molecular Architecture ◽

Ngs Data ◽

Acute Myeloid

7024 Background: Extramedullary (EM) involvement, including myeloid sarcoma (MS) and leukemia cutis (LC), is uncommon in patients with acute myeloid leukemia (AML). Mutational landscape of EM-AML is not well characterized, including concordance of sequencing data from EM vs. non-EM site (blood or bone marrow) and the potential for personalized targeted therapy in this patient cohort. Methods: In a multicenter retrospective study, clinical and genomic data were collected on EM-AML patients treated at Moffitt Cancer Center, Memorial Healthcare System, and University of Miami, as well as sequenced cases at a central laboratory. Next generation sequencing (NGS) data come from panels that interrogated 24- 406 genes, with 15 genes covered by all panels, including notably, IDH1, IDH2, KIT, KRAS, NPM1, NRAS, and TP53. Survival estimates using Kaplan-Meier statistics and multivariate analysis with Cox-regression were performed in SPSS (v.26). Results: Our study included 58 patients with EM-AML. Median age at diagnosis was 62 years; 55% of patients were males. In our cohort, 34 (59%) patients had MS, and 19 (33%) had LC. EM-AML was noted during relapse in 60% of evaluable patients (n=45), and 31% had isolated EM disease. Patients with LC had a significantly worse median overall survival (OS) than those with MS (5.7 months vs. 21.9 months, p= 0.008); Pattern of EM involvement (MS vs. LC) remained an independent prognostic factor for OS (p= 0.04) in a multivariate analysis including disease setting (new diagnosis vs. relapse) and ELN risk category. Results of NGS performed during EM presentation were available in 48 patients, 19 of which had NGS data from EM site. Most commonly mutated genes were NRAS on EM site NGS (37%) and NPM1 on non-EM site NGS (28%). Based on EM NGS, 52% patients had a targetable genomic alteration, with 37% mutations in IDH, 21% NPM1, 5% FLT3, and 11% MLL-PTD. Five (two with concurrent M+EM disease) out of nine evaluable patients had significant discordance in targetable mutations between EM and non-EM NGS at EM-AML. Three of four patients who received treatment with IDH1/2 inhibitors based on EM NGS achieved complete response. Conclusions: EM-AML has a distinct molecular architecture with an inferior OS in LC vs. MS patients. We conclude that EM site NGS is critical in patients with EM-AML, as 52% have potentially targetable mutations and could benefit from specific targeted therapies.[Table: see text]

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Delays in time to antibiotics in inpatient oncologic neutropenic fever do not predict decreased overall survival.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18765 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18765-e18765

Author(s):

Jordan Villars ◽

Christopher Anand Gardner ◽

Tingting Zhan ◽

Adam F Binder

Keyword(s):

Overall Survival ◽

Black People ◽

Cox Regression ◽

Adverse Outcomes ◽

Neutropenic Fever ◽

Cancer Center ◽

Common Disease ◽

Inpatient Setting ◽

Oncologic Patients ◽

Time To Antibiotics

e18765 Background: Neutropenic fever (NF) is relatively common oncologic emergency. Present expert consensus is that anti-pseudomonas gram-negative antibiotics should be administered within 60 minutes of detecting NF. To date studies investigating this relationship in neutropenic fever patients have been either limited in size, or have failed to reliably establish a relationship between time to antibiotics (TTA) and clinical outcomes.While some studies have shown an association between TTA and outcomes in NF patients admitted from the Emergency Department, such studies do not control for the time that patients may have been febrile in the community. To address these factors, we conducted a retrospective study on the effect of TTA on mortality in oncologic patients who developed NF as inpatients. Methods: We performed retrospective chart review of all cases of NF at an NCI designated Cancer Center between 7/1/2016 and 3/27/2019. NF was defined as temperature of 101˚ F on one occasion, or 100.4˚ F sustained over 60 minutes, with an absolute neutrophil count (ANC) less than 500. TTA and survival were calculated via chart abstraction; patients lost to follow up within 180 days were censored to the 180-day mortality group. Relationship between TTA and overall survival (OS) was analyzed via multivariable Cox regression. We excluded patients that had non-cancer related NF, were transferred from another institution with NF, were admitted from the ED with NF, or transitioned to hospice. Only the first instance of NF in any admission was analyzed. Results: A total of 187 eligible cases were identified during the study period, mean age was 57.6 +/- 13.6, 100 (53.5%) cases were in males, 114 (61.0%) cases in Caucasians, 53 (28.3%) in Black People. The 3 most common disease subtypes were acute leukemia (42.8%), plasma cell dyscrasias (27.8%), and lymphoma (16.6%). TTA showed no significant correlation with OS at any timeframe studied. Low Charlson Comorbidity Index ( < 3) correlated with increased survival through ̃360 days, however the effect was non-significant at longer timeframes. Immediate antibiotic treatment ( < 40 mins) correlated with poorer patient prognosis and significantly decreased OS (HR 3.08;CI: 1.30-7.28; p 0.010). Conclusions: TTA was not associated with OS in our study. For inpatients with NF, even hours long TTA may not be long enough to result in adverse clinical outcomes. Unlike NF patients presenting to the ED, where true TTA may often be many hours or even days prior to arrival, a few hours-long TTA in the hospital may not be sufficiently long enough to cause significant patient harm. Interestingly, in our cohort, those who received antibiotics quickly had adverse outcomes. It may be that in patients who were clinically unstable, TTA was shorter given the urgency of the situation. Ultimately, this study’s findings question the applicability of the 60-minute guideline when used in the inpatient setting.

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