Analysis of radiotherapy impact on survival in resected stage I/II pancreatic cancer patients: a population-based study

Abstract Background The application of radiotherapy (RT) in pancreatic cancer remains controversial. Aim The aim of the study was to evaluate the efficacy of radiotherapy (neoadjuvant and adjuvant radiotherapy) for resectable I/II pancreatic cancer. Methods Fourteen thousand nine hundred seventy-seven patients with pancreatic cancer were identified from SEER database from 2004 to 2015. Multivariate analyses were performed to determine factors including RT on overall survival. Overall survival and overall mortality among the different groups were evaluated using the Kaplan-Meier method and Gray’s test. Results Patients were divided into groups according to whether they received radiotherapy or not. The median survival time of all 14,977 patients without RT was 20 months, neoadjuvant RT was 24 months and adjuvant RT was 23 months (p < 0.0001). Median survival time of 2089 stage I patients without RT was 56 months, significantly longer than those with RT regardless of neoadjuvant or adjuvant RT (no RT: 56 months vs adjuvant RT: 37 months vs neoadjuvant RT: 27 months, P = 0.0039). Median survival time of 12,888 stage II patients with neoadjuvant RT was 24 months, adjuvant RT 22 months, significantly prolonged than those without radiotherapy (neoadjuvant RT: 24 months vs adjuvant RT: 22 months vs no RT: 17 months, P<0.0001). Neoadjuvant RT (HR = 1.434, P = 0.023, 95% CI: 1.051–1.957) was independent risk factors for prognosis of stage I patients, and adjuvant RT (HR = 0.904, P < 0.001, 95% CI: 0.861–0.950) predicted better outcomes for prognosis of stage II patients by multivariate analysis. The risk of cancer-related death caused by neoadjuvant RT in stage I and no-RT in stage II patients were significantly higher. Conclusions The study identified a significant survival advantage for the use of adjuvant RT over surgery alone or neoadjuvant RT in treating stage II pancreatic cancer. RT was not associated with survival benifit in stage I patients.

Download Full-text

Analysis of radiotherapy impact on survival in resected stage I/II pancreatic cancer patients: a population-based study

10.21203/rs.3.rs-126795/v2 ◽

2021 ◽

Author(s):

Dong Han ◽

Fei Gao ◽

JinLong Liu ◽

Hao Wang ◽

Qi Fu

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Survival Time ◽

Median Survival ◽

Median Survival Time ◽

Population Based ◽

Stage I ◽

Stage Ii ◽

Resected Stage ◽

Risk Of Cancer

Abstract Background: The application of radiotherapy (RT) in pancreatic cancer remains controversial. Aim: The aim of the study was to evaluate the efficacy of radiotherapy (neoadjuvant and adjuvant radiotherapy) for resectable I/II pancreatic cancer. Methods: 14977 patients with pancreatic cancer were identified from SEER database from 2004 to 2015. Multivariate analyses were performed to determine factors including RT on overall survival. Overall survival and overall mortality among the different groups were evaluated using the Kaplan-Meier method and Gray’s test. Results: Patients were divided into groups according to whether they received radiotherapy or not. The median survival time of all 14977 patients without RT was 20 months, neoadjuvant RT was 24 months and adjuvant RT was 23 months (p < 0.0001) . Median survival time of 2089 stage I patients without RT was 56 months, significantly longer than those with RT regardless of neoadjuvant or adjuvant RT (no RT: 56 months vs adjuvant RT: 37 months vs neoadjuvant RT: 27 months, P=0.0039). Median survival time of 12888 stage II patients with neoadjuvant RT was 24 months, adjuvant RT 22 months, significantly prolonged than those without radiotherapy(neoadjuvant RT: 24 months vs adjuvant RT: 22 months vs no RT: 17 months, P＜0.0001). Neoadjuvant RT (HR=1.434, P=0.023, 95% CI: 1.051-1.957) was independent risk factors for prognosis of stage I patients, and adjuvant RT (HR=0.904, P < 0.001, 95% CI: 0.861-0.950) predicted better outcomes for prognosis of stage II patients by multivariate analysis. The risk of cancer-related death caused by neoadjuvant RT in stage I and no-RT in stage II patients were significantly higher. Conclusions: The study identified a significant survival advantage for the use of adjuvant RT over surgery alone or neoadjuvant RT in treating stage II pancreatic cancer. RT was not associated with survival benefit in stage I patients.

Download Full-text

Analysis of Radiotherapy Impact on Survival in Resected Stage I/ii Pancreatic Cancer Patients: A Population-based Study

10.21203/rs.3.rs-126795/v1 ◽

2020 ◽

Author(s):

Dong Han ◽

Fei Gao ◽

JinLong Liu ◽

Hao Wang ◽

Qi Fu

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Survival Time ◽

Median Survival ◽

Median Survival Time ◽

Population Based ◽

Stage I ◽

Stage Ii ◽

Resected Stage ◽

Risk Of Cancer

Abstract Background: The application of radiotherapy (RT) in pancreatic cancer remains controversial. The aim of the study was to evaluate the efficacy of radiotherapy (neoadjuvant and adjuvant radiotherapy) for resectable I/II pancreatic cancer. Methods: 14977 patients with pancreatic cancer were identified from SEER database from 2004 to 2015. Multivariate analyses were performed to determine factors including RT on overall survival. Overall survival and overall mortality among the different groups were evaluated using the Kaplan-Meier method and Gray’s test. Results: Patients were divided into groups according to whether they received radiotherapy or not. The median survival time of all 14977 patients without RT was 20 months, neoadjuvant RT was 24 months and adjuvant RT was 23 months (p < 0.0001) . Median survival time of 2089 stage I patients without RT was 56 months, significantly longer than those with RT regardless of neoadjuvant or adjuvant RT (no RT: 56 months vs adjuvant RT: 37 months vs neoadjuvant RT: 27 months, P=0.0039). Median survival time of 12888 stage II patients with neoadjuvant RT was 24 months, adjuvant RT 22 months, significantly prolonged than those without radiotherapy(neoadjuvant RT: 24 months vs adjuvant RT: 22 months vs no RT: 17 months, P＜0.0001). Neoadjuvant RT (HR=1.434, P=0.023, 95% CI: 1.051-1.957) was independent risk factors for prognosis of stage I patients, and adjuvant RT (HR=0.904, P < 0.001, 95% CI: 0.861-0.950) predicted better outcomes for prognosis of stage II patients by multivariate analysis. The risk of cancer-related death caused by neoadjuvant RT in stage I and no-RT in stage II patients were significantly higher. Conclusions: The study identified a significant survival advantage for the use of adjuvant RT over surgery alone or neoadjuvant RT in treating stage II pancreatic cancer. RT was not associated with survival benifit in stage I patients.

Download Full-text

A Clinicopathological Analysis on Diffuse Midline Glioma in Adults

10.21203/rs.3.rs-507531/v1 ◽

2021 ◽

Author(s):

Xiao Mu Hu ◽

Xiao Yu Nie ◽

Kai Lun Xu ◽

Yin Wang ◽

Feng Tang ◽

...

Keyword(s):

Overall Survival ◽

Survival Time ◽

Median Survival ◽

Median Survival Time ◽

Age Groups ◽

Young Patients ◽

Imaging Data ◽

Wild Type ◽

Old Patients ◽

Diffuse Midline Glioma

Abstract Purpose: Diffuse midline glioma (DMG), H3K27M mutant is a new entity that has become widely recognized. However, studies concerning DMG in adult patients remains rare. We did a retrospective study covering the largest amount of patients to date to analyze the clinicopathological characteristics of DMG in adult. Methods: We reviewed 117 cases of adult DMG, collected their clinical and imaging data along with pathological results including H3K27M. Summarized their features and the connection with overall survival in different age groups.Results: Among 117 cases, most tumors were located at the thalamus, 39 patients had H3K27M mutation, of whom 38 demonstrated down regulation of H3K27me3. The average overall survival of H3K27M-mutant gliomas was 13 months, while that of 78 H3K27M wild-type gliomas were 11.8 months. For young patients (age＜35), The median survival time of the H3K27M-mutant was 20.1 months, while that of the H3K27M wild-type was 39.5 months. For older patients (age≥35), the median survival time of the H3K27M-mutant was 22.3 months, while that of the H3K27M wild-type was 17.1 months. The OS of patients who received biopsies, subtotal resections, and total resections were 15.8, 17.6, and 11.6 months respectively. Conclusion: The DMG in adults mainly occurred in the thalamus. H3K27M mutations tend to happen more frequently in young adults, and this genetic alteration results in a worse outcome only in young patients. For old patients, age and the approach of surgery are independent prognostic factors. Patients received biopsy instead of total resection had a better prognosis.

Download Full-text

OR25-07 A Multi-Center, Open-Label, Pivotal Phase 2 Study of Azedra® (HSA I-131-MIBG) in Patients with Unresectable, Locally Advanced or Metastatic Pheochromocytoma or Paraganglioma: Updated Long-Term Survival and Safety

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1241 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Camilo Jimenez ◽

Bennett B Chin ◽

Richard B Noto ◽

Joseph Stephen Dillon ◽

Lilja B Solnes ◽

...

Keyword(s):

Overall Survival ◽

Survival Time ◽

Median Survival ◽

Median Survival Time ◽

Locally Advanced ◽

Phase 2 ◽

Pivotal Phase ◽

Term Survival ◽

Phase 2 Study ◽

Therapeutic Doses

Abstract Background: Pheochromocytoma/Paraganglioma (PPGL) are rare neuroendocrine tumors with a 5-yr survival rate as low as 12%. There is a high unmet medical need for effective treatment options for patients with advanced disease. AZEDRA®, a high-specific-activity iodine-131 meta-iodobenzylguanidine (HSA I-131-MIBG), is the first and only FDA-approved therapeutic radiopharmaceutical agent indicated for the treatment of adult and pediatric patients with iobenguane scan positive, unresectable, locally advanced or metastatic PPGL who require systemic anticancer therapy. Methods: Patients with advanced PPGL who were heavily pre-treated and were ineligible for curative surgery or chemotherapy received a dosimetric dose followed by up to two therapeutic doses (each at 296 MBq/kg to a max of 18.5 GBq). The primary endpoint, defined as the proportion of patients with at least 50% reduction of all antihypertensive medication(s) lasting ≥6 months, was met and previously reported. Updated secondary endpoints including overall survival (OS) and safety are reported. Results: A dosimetric dose of HSA I-131-MIBG was administered to 74 patients. Of those, 68 patients received one therapeutic dose and 50 received two doses of HSA I-131-MIBG. Clinical benefit rates (objective tumor responses defined by RECIST 1.0 and stable disease) were observed in 71.4% and 98.0% of patients receiving one and two therapeutic doses, respectively. As of October 10, 2019, median survival time for all patients was 43.2 months (95% CI 31.4, >60). Median survival time was 19.3 months (95% CI 4.5, 32.4) and 49.1 months (95% CI 36.9, >60) in patients receiving one and two doses, respectively. The overall survival was 73.8% at 2 yrs, 47.5% at 4 yrs and 41.5% at 5 yrs. The most common (≥50%) adverse events were nausea, fatigue, and myelosuppression. Myelosuppressive events resolved within 4-8 wks without requiring stem cell transplantation. Late radiation toxicity included 7 patients with secondary malignancies (myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), colon cancer, and lung carcinoma) of which MDS, ALL and AML were considered related to I-131 radiotherapy. Conclusions: Results from this pivotal phase 2 study suggest that HSA I-131-MIBG is an efficacious and safe treatment for advanced PPGL.

Download Full-text

Controlling Nutritional Status (CONUT) Score is Associated with Overall Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib: A Multicenter Cohort Study

Nutrients ◽

10.3390/nu12041076 ◽

2020 ◽

Vol 12 (4) ◽

pp. 1076 ◽

Cited By ~ 1

Author(s):

Shigeo Shimose ◽

Takumi Kawaguchi ◽

Hideki Iwamoto ◽

Masatoshi Tanaka ◽

Ken Miyazaki ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Nutritional Status ◽

Survival Time ◽

Median Survival ◽

Median Survival Time ◽

Rank Test ◽

Multicenter Cohort Study ◽

The Impact ◽

Conut Score

We aimed to investigate the impact of the controlling nutritional status (CONUT) score, an immuno-nutritional biomarker, on the prognosis of patients with hepatocellular carcinoma (HCC) treated with lenvatinib (LEN). This retrospective study enrolled 164 patients with HCC and treated with LEN (median age 73 years, Barcelona Clinic Liver Cancer (BCLC) stage B/C 93/71). Factors associated with overall survival (OS) were evaluated using multivariate and decision tree analyses. OS was calculated using the Kaplan–Meier method and analyzed using the log–rank test. Independent factors for OS were albumin–bilirubin grade 1, BCLC stage B, and CONUT score <5 (hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.58–5.31, p < 0.001). The CONUT score was the most important variable for OS, with OS rates of 70.0% and 29.0% in the low and high CONUT groups, respectively. Additionally, the median survival time was longer in the low CONUT group than in the high CONUT group (median survival time not reached vs. 11.3 months, p < 0.001). The CONUT score was the most important prognostic variable, rather than albumin–bilirubin grade and BCLC stage, in patients with HCC treated with LEN. Accordingly, immuno-nutritional status may be an important factor in the management of patients with HCC treated with LEN.

Download Full-text

A phase II multicentric trial of combined chemotherapy with gemcitabine plus S-1 in patients with advanced pancreatic cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15129 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15129-15129

Author(s):

S. Ohkawa ◽

A. Amano ◽

M. Ueno ◽

K. Miyakawa ◽

K. Sugimori ◽

...

Keyword(s):

Pancreatic Cancer ◽

Phase I ◽

Survival Time ◽

Median Survival ◽

Phase Ii ◽

Median Survival Time ◽

Progressive Disease ◽

Advanced Pancreatic Cancer ◽

Combined Chemotherapy ◽

Standard Drug

15129 Background: While gemcitabine (GEM) is the standard drug for chemotherapy against advanced pancreatic cancer, the development of multidrug therapies for improved outcome is important. We conducted multicentric combined chemotherapy with GEM and S-1 trial and reported the results of the phase I trial last year. And this phase II study evaluated the efficacy and feasibility. Methods: The subjects had unresectable pancreatic ductal cancer. Eligibility criteria were pathologically-proven, Karnofsky performance status 80 to 100%, age 20 to 74 years, adequate hematological, renal, and liver functions and written informed consent. The method of administration was single administration of GEM on the first day of the week 1000 mg/m2, with concurrent administration of S-1 at 80 (<1.5 m2) to 100 (=1.5 m2) mg/day × 7 days, repeated every other week until the progressive disease or life threatening adverse events. This administration dose was determined from the result of the phase I study. The primary endpoint was median survival time. And the secondary endpoints were the overall response rate and the toxicities. Results: 40 patients(pts) were enrolled. Average age was 62.9±8.3 years (34–73 years). Thirty nine pts were conducted this therapy except one who refused this study before the start of administration. Thirty eight pts were evaluable for response, partial response, stable disease, progressive disease were observed in 7 (17.5%), 21 (52.5%) and 10 pts (25.0%), respectively. The median survival time at this stage is 276±51 days in this ongoing study. Grade 3 and 4 toxicities were mainly leucocytes(10 pts), neutrophils(8 pts) and anorexia(6 pts). Conclusions: The GEM plus S-1 combined chemotherapy is effective and feasible in patients with advanced pancreatic cancer. No significant financial relationships to disclose.

Download Full-text

An assessment of the impact of geographic variation on resection rates and survival for early-stage pancreatic adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15052 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15052-e15052

Author(s):

Bradley D. McDowell ◽

Brian J. Smith ◽

Anna M Button ◽

James R. Howe ◽

Elizabeth A. Chrischilles ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Pancreatic Adenocarcinoma ◽

Early Stage ◽

Stage I ◽

Stage Ii ◽

Survival Times ◽

Resection Rate ◽

Selection Factors ◽

The Impact

e15052 Background: Pancreatic resection is the only known curative option for pancreatic adenocarcinoma. Resection has been previously reported to be underutilized in patients with early stage disease. To develop a better understanding of this issue and control for treatment selection factors, we examined the relationship between geographic area resection rates and survival in patients with stage I/II pancreatic cancer. Methods: We queried Surveillance, Epidemiology, and End Results (SEER) data for patients with stage I/II cancer of the pancreatic head diagnosed from 2004-2009. We excluded patients with less than 3mo survival. Resection rates were calculated within Health Service Areas (HSAs) across all 18 SEER regions. Resection rate was defined as the number of patients who had an operation divided by the total number diagnosed with early stage pancreatic cancer. Multivariate Cox regression was used to estimate the overall survival effect of HSA rates while controlling for age, gender, marital status, poverty level, education, and AJCC stage. Results: 8,323 patients with stage I (n=1,454) and stage II (n=6,869) disease were analyzed. Pancreatectomy was performed in 476 patients (32.7%) with stage I disease and 3,846 (56.0%) with stage II disease. HSA resection rates were arranged into five groups (quintiles) which ranged from 42.7 to 65.7% (Table). Across the quintiles, median overall survival increased from 11 to 14 months, suggesting a positive association with resection rate. Multivariate analysis revealed that for every 10.00% increase in resection rate, the risk of overall death decreased by 5.26% (p<0.001). Conclusions: Patients with early stage pancreatic cancer who live in areas with higher resection rates have longer average survival times. Because geography should not influence treatment response, we conclude that efforts to raise resection rates should increase survival times in patients for whom there is uncertainty about the risk/benefits of resection. [Table: see text]

Download Full-text

A 10-year Retrospective Study of Lung Cancer in Uganda

10.21203/rs.3.rs-1172897/v1 ◽

2021 ◽

Author(s):

Naghib Bogere ◽

Felix Bongomin ◽

Andrew Katende ◽

Blair Andrew Omaido ◽

Elizabeth Namukwaya ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Survival Time ◽

Median Survival ◽

Medical Records ◽

Median Survival Time ◽

Histological Diagnosis ◽

Histologic Subtype ◽

Vital Status ◽

Phone Calls

Abstract Background: Lung cancer is a leading cause of cancer-related deaths in Uganda. In this study, we aimed to describe the baseline characteristics and survival of patients with lung cancer at Uganda Cancer Institute (UCI). Methodology: We retrospectively reviewed medical records of all patients with a histological diagnosis of lung cancer registered at UCI between January 2008 and August 2018. Data on demographic, clinical, and treatment characteristics, and vital status were abstracted and analyzed. Patients with undocumented vital status on the medical records were contacted through phone calls. We determined survival as time from histological diagnosis to death. The Kaplan-Meier survival analysis was performed to estimate the median survival time and the 5-year overall survival rate. Results: Of the 207 patients enrolled, 56.5% (n=117) were female, median age was 60 years (range: 20-94), 78.7% (n=163) were never-smokers and 18 (8.7%) were living with HIV. Presumptive anti-tuberculosis treatment was given to 23.2% (n=48). Majority had non-small cell lung cancer (96.6%, n=200) with 74.5% (n=149) adenocarcinoma and 19% (n=38) squamous cell carcinoma. All had advanced (stage III or IV) disease with 96.1% (n=199) in stage IV. Chemotherapy (44.9%, n=93) and biological therapy (34.8%, n=72) were the commonest treatments used. Overall survival at 6 months, 1-, 2- and 5-years was 41.7%, 29.7%, 11.8% and 1.7% respectively. The median survival time was 4.4 months and was not different between NSCLC and SCLC (4.5 vs. 3.9 months respectively, p=.335). Conclusion: In Uganda, adenocarcinoma is the predominant histologic subtype of lung cancer predominantly occurring in females and non-smokers. Patients present late with advanced disease and poor overall survival. Public awareness should be heightened to facilitate early screening and improve outcomes.

Download Full-text

Prognostic Significance of K-ras Codon 12 Mutations in Patients With Resected Stage I and II Non–Small-Cell Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.2.668 ◽

1999 ◽

Vol 17 (2) ◽

pp. 668-668 ◽

Cited By ~ 135

Author(s):

Stephen L. Graziano ◽

Gary P. Gamble ◽

Nancy B. Newman ◽

Lynn Z. Abbott ◽

Michelle Rooney ◽

...

Keyword(s):

Median Survival ◽

Squamous Cell ◽

Early Stage ◽

Prognostic Significance ◽

Stage I ◽

Stage Ii ◽

Small Cell Lung ◽

Ras Mutations ◽

Significant Difference ◽

Resected Stage

PURPOSE: The aim of this study was to investigate the prognostic importance of codon 12 K-ras mutations in patients with early-stage non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We identified 260 patients with surgically resected stage I (n = 193) and stage II (n = 67) NSCLC with at least a 5-year follow-up. We performed polymerase chain reaction analysis of DNA obtained from paraffin-embedded NSCLC tissue, using mutation-specific probes for codon 12 K-ras. RESULTS: K-ras mutations were detected in 35 of 213 assessable specimens (16.4%). K-ras mutations were detected in 27 of 93 adenocarcinomas (29.0%), one of 61 squamous cell carcinomas (1.6%), five of 39 large-cell carcinomas (12.8%), and two of 20 adenosquamous carcinomas (10%) (P = .001). G to T transversions accounted for 71% of the mutations. There was no statistically significant difference in overall survival for all patients with K-ras mutations (median survival, 39 months) compared with patients without K-ras mutations (median survival, 53 months; P = .33). There was no statistically significant difference in overall or disease-free survival for subgroups with stage I disease, adenocarcinoma, or non–squamous cell carcinoma or for specific amino acid substitutions. The median survival time for stage II patients with K-ras mutations was 13 months, compared with 38 months for patients without K-ras mutations (P = .03). CONCLUSION: Codon 12 K-ras mutations were more common in adenocarcinomas than in squamous cell carcinomas. For the subgroup with stage II NSCLC, there was a statistically significant adverse effect on survival for the presence of K-ras mutations. However, when the entire group was considered, the presence of K-ras mutations was not of prognostic significance in this cohort of patients with resected early-stage NSCLC.

Download Full-text

The Predictive Value of TP53 FISH Analysis for Treatment Response and Survival in Cytogenetic Subgroups of AML Patients.

Blood ◽

10.1182/blood.v114.22.2617.2617 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2617-2617

Author(s):

Sigal Tavor ◽

Rachel Rothman ◽

Tamar Golan ◽

Nadia Voskoboinik ◽

Ruth Shomrat ◽

...

Keyword(s):

Overall Survival ◽

Survival Time ◽

Median Survival ◽

Predictive Value ◽

Cytogenetic Analysis ◽

Median Survival Time ◽

Allogeneic Transplantation ◽

Fish Analysis ◽

Chromosomal Deletions ◽

Tp53 Status

Abstract Abstract 2617 Poster Board II-593 In recent years, a number of studies emphasized AML with complex aberrant karyotype as a distinct biological entity which is characterized by a unique gene expression pattern, with very frequent alteration in TP53 and a median overall survival (OS) of less than 6 months. However, the definition of a complex karyotype (CK) or whether monosomal karyotype (MK) provides a better prognostic prediction than CK is not well established. In the present study, we examined whether a prompt and simple Fluorescence in situ hybridization (FISH) test for TP53 deletion (presence or absence of 17p13) at diagnosis, has a predictive value for response to therapy and overall survival in AML patients (pts) with CK or chromosomal deletions (either complete or partial of any other chromosome). Between 2000 and 2009 we analyzed 38 patients with newly diagnosed AML, with age ranged from 18 to 82 years (median 52 years). On cytogenetic analysis from bone marrow at diagnosis, 16 (42%) pts had a CK (≥3 chromosome abnormalities), 16 pts (42%) had a normal karyotype (NK) and 6 (16%) pts had other monosomy or deletion of any chromosomal region. Seven patients had a post myelodysplastic syndrome AML and 1 post therapy for a prior malignancy. For induction treatment patients received idarubicine, 12 mg/m2/d (age 18– 55y) or mitoxantron 10 mg/m2/d intravenous (IV) on days 1-3 (age 55–68y) and cytarabine, 100mg/m2/d by continuous IV infusion on days 1 through 7. Pts entering complete remission (CR) received three courses of consolidation with high dose cytarabine. Patients with a histocompatibale donor, which did not received CR or relapsed, were allografted. Elderly patients, 69–82 years old, were treated with one induction chemotherapy which included Mylotarg (3mg/m2/2h on day 1) plus cytarabine (100 mg/m2/24h on days 2-8). Patients at this group of age did not received consolidation therapy. Of the16 pts with CK AML, 14 were treated with chemotherapy but only 3 pts (21%) achieved CR, 4 pts died during induction therapy. By comparison, of the 16 pts with NK AML, 15 pts were treated with chemotherapy, 11 pts achieved CR (73%), 3 pts died during induction therapy. Of the 6 AML pts with monosomy or deletion in cytogenetic analysis, 3 pts (50%) achieved CR (p =0.0067). In all NK AML patients examined the TP53 FISH was normal (mean 4% of cells examined), where as in patient with CK 75% of pts had TP53 deletion (mean 51%), and in the group with chromosomal deletion 50% of pts showed a loss of one TP53 (mean 18%) p=0.0016. Of note, in 13 pts (34%) with TP53 deletion by FISH analysis, cytogenetic analysis found no anomaly of 17p chromosome. In a stepwise logistic regression model FISH groups significantly entered the model in first step, and no other variable did (p=0.0056, C=0.833). In pts in which two copies of TP53 were found in FISH analysis ('10%) the median survival time is 440 days, whereas in pts with TP53 deletion was detected the median survival time was 189 days. The OS in pts with deletion of TP53 was significantly shorter as compared to pts that TP53 deletion was not found (p=0.025). However, a multivariate analysis including age, karyotype, deletion of TP53 and allogeneic transplantation showed that only CK and allogeneic transplantation are independent prognostic factors in this analysis. In conclusion, TP53 status by FISH at diagnosis is important due to the following findings: The test is sensitive, rapid and simple. 2. TP53 deletions are frequent in AML with CK and tend to segregate with additional chromosomal deletions. TP53 status at diagnosis has a predictive value with respect to chemotherapy response and OS in AML pts with CK and chromosomal deletions. Disclosures: No relevant conflicts of interest to declare.

Download Full-text