Outcome of patients with colorectal cancer undergoing lung metastases resection: a single-institution retrospective analysis

Introduction: This study was undertaken to review a single-institution cohort of patients with metastatic colorectal cancer undergoing lung resection after a multidisciplinary evaluation and to investigate the main prognostic factors for survival. Methods: Medical records of 129 patients undergoing lung metastasectomy for colorectal cancer with curative intent from 2001 to 2017 were reviewed. Tissue samples from the primary tumor were analyzed with a multiplex genotyping system for the detection of mutations in RAS and BRAF genes. Survival analyses were carried out by the Kaplan-Meier method. Univariate and multivariable analyses were performed using the log-rank test and the Cox regression model. Results: Postoperative morbidity and mortality were 13.2% and 0%, respectively. At a median follow-up time of 62.5 months, median overall survival was 90.5 months and median relapse-free survival was 42.8 months. Multivariable analysis for overall survival identified synchronous versus metachronous metastatic presentation as the only prognostic factor, whereas relapse-free survival was independently associated with synchronous versus metachronous metastatic presentation, number of metastases, and postoperative chemotherapy. Conclusions: This study shows particularly favorable survival outcomes for patients undergoing lung metastasectomy. The validity of some of the main prognostic factors was confirmed and a positive effect of postoperative chemotherapy on relapse-free survival was shown. Contrary to other reports, the presence of KRAS mutations was not associated with significant survival differences. Further studies are needed in order to clarify the interactions between molecular, clinical, and pathologic characteristics and treatment-related factors.

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Aspirin in the prevention of colorectal cancer recurrence.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.578 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 578-578

Author(s):

Nimisha Kumari ◽

Hiren A. Mandaliya ◽

Tiffany Evans ◽

Patrick McElduff ◽

Christopher Oldmeadow ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Chemotherapy ◽

Regression Model ◽

Propensity Scores ◽

Cox Regression ◽

Colorectal Adenomas ◽

Stage Ii ◽

Single Institution ◽

Relapse Free Survival ◽

Free Survival

578 Background: Aspirin use reduces the incidence of colorectal adenomas, and of colorectal cancer (CRC) in patients with hereditary non-polyposis colorectal cancer. There is limited data on the effect of aspirin in the secondary prevention of CRC, currently the subject of multiple prospective randomized trials. We aimed to test the hypothesis that aspirin reduces disease recurrence in patients diagnosed with early CRC at a high volume, single institution. Methods: A retrospective analysis was conducted of all patients (pts) treated with at least one cycle of adjuvant chemotherapy for stage II or III CRC over a 5yr period (2009–13). Patients with synchronous CRC were excluded. Aspirin use at the onset of adjuvant chemotherapy was sourced from the universal electronic recording of concomitant medications. Kaplan-Meier curves and the log-rank test were used to compare crude relapse free survival (RFS) between pts who were using aspirin to those who were not. Propensity score analyses was used to balance the groups according to potentially confounding variables: tumor site (colon vs rectum), tumor stage (II vs III), and adjuvant chemotherapy (oxaliplatin-based vs no oxaliplatin). The propensity scores were estimated through a multivariable logistic regression model, and a Cox proportional hazards model used to assess the effect of aspirin use on RFS in the sample weighted according to the inverse probability of receiving aspirin. Results: A cohort of 231 pts met eligibility criteria; median age 64yr; 50% colon, 50% rectal; 19% stage II, 81% stage III; 35% received oxaliplatin; 13% (n=31) were using aspirin and 26% of pts (n=61) developed CRC recurrence in median follow-up of 2.9yr. Unadjusted RFS was not significantly different for those using aspirin (log rank p value 0.88). There was good overlap in propensity scores for the two groups. The hazard ratio for RFS with aspirin use from the weighted Cox regression model was 1.2 (95% CI 0.62-2.29), indicating no statistically significant effect of aspirin on CRC relapse. Conclusions: In this single institution series, we did not find evidence that aspirin use at onset of chemotherapy had an effect on CRC relapse free survival. These results do not exclude an aspirin effect that is modest or restricted to select CRC subgroups.

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Prognostic facctor for early versus late relapse in hormonodependant non metastatic breast cancers treated by tamoxifen: PROFARE study results from GETNA group

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.10585 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 10585-10585

Author(s):

D. Azria ◽

M. Tubiana-Hulin ◽

M. Spielmann ◽

B. Coudert ◽

A. Monnier ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Survival Time ◽

Cox Regression ◽

Late Relapse ◽

Lower Quartile ◽

Relapse Free Survival ◽

Free Survival ◽

Early Relapse

10585 Background: The purpose of this study was to identify potential prognostic factors of early relapse among postmenopausal women with ER+ breast cancer treated at least by adjuvant tamoxifen therapy. Methods: This was a multi-center, retrospective study. Data was collected from 1588 subjects on demographic and subject characteristics and the subjects’ course of the disease using information from patient files. It was planned to have data to cover a follow-up period of ten years. Frequency distributions of the pre-specified potential prognostic factors were presented for subjects with relapse or death (RoD) below 3 years (early), RoD after at least 3 years (late) and without RoD recorded. Results: There were 1550 subjects included in the analysis population. The median age was 60 years [52–67]. There were 633 patients (40.8%) with an event for RoD. Median relapse-free survival time (RFS) was 165 months (no confidence interval calculation possible due to low event rate) and lower quartile relapse-free survival time was 68 months [95% CI, 59–76]. Concerning RFS 212 (13.7%) subjects had an early relapse and 421 (31.5%) had a late relapse. Out of 1550 subjects analyzed for overall survival, there were 344 (22.2%) with an event. Median survival time was not reached; lower quartile survival time was 143 months [131–176 months]. The Cox regression for RFS showed that prognostic factors for RFS overall and for early RFS seems to have similar patterns. Prognostic factors for late RFS differed from those for RFS overall and early RFS. The Cox regression for overall survival showed similar results. SBR grade 1 or 2 vs. 3 (p < 0.0001), <4 vs. ≥4 lymph nodes involved (p < 0.0001), and tumor size pT0–1 vs pT2–4 (p = 0.0001) are selected in both models as prognostic factors. These factors are also of prognostic value for RFS. Conclusions: Women with hormonodependant breast cancer who are at high risk of early relapse while on tamoxifen can potentially be identified. These data could maybe be of importance concerning the choice of the upfront hormonal regimen in menopaused women treated for hormonodependant breast cancer. No significant financial relationships to disclose.

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Circulating inflammation signature predicts overall survival and relapse-free survival in metastatic colorectal cancer

British Journal of Cancer ◽

10.1038/s41416-018-0360-y ◽

2019 ◽

Vol 120 (3) ◽

pp. 340-345 ◽

Cited By ~ 3

Author(s):

Andreas Varkaris ◽

Anastasia Katsiampoura ◽

Jennifer S. Davis ◽

Neeraj Shah ◽

Michael Lam ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Metastatic Colorectal Cancer ◽

Relapse Free Survival ◽

Free Survival

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The Impact of Rituximab and Radiotherapy On Treatment Outcome of Patients with DLBCL and Skeletal Involvement

Blood ◽

10.1182/blood.v120.21.690.690 ◽

2012 ◽

Vol 120 (21) ◽

pp. 690-690

Author(s):

Gerhard Held ◽

Samira Zeynalova ◽

Niels Murawski ◽

Marita Ziepert ◽

Barbara Kempf ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Cox Regression ◽

Multivariable Analysis ◽

Event Free Survival ◽

Advisory Committees ◽

Free Survival ◽

Skeletal Involvement ◽

The Impact

Abstract Abstract 690 Background: There is limited information on the role of skeletal involvement in DLBCL patients treated with rituximab. Methods: In a retrospective subgroup analysis patients with aggressive B-cell lymphomas with and without skeletal involvement were compared with respect to clinical presentation, event-free and overall survival. Results: Of 3840 patients 292 (7.6%) had skeletal involvement. In a multivariable analysis of patients treated within the randomized MInT and RICOVER-60 trials, the two largest randomized trials addressing the role of rituximab in DLBCL to date, skeletal involvement was associated with a reduced hazard ratio (HR) of 0.8 (p=0.181) for event-free survival and 0.7 (p=0.083) for overall survival for patients treated without, but with an increased HR (1.5; p=0.048) for event-free and (1.1; p=0.828) for overall survival in patients treated with rituximab. This was due to the failure of rituximab to improve the outcome of patients with skeletal involvement. In the MInT trial, the 3-year EFS rates were 64% without and 63% with rituximab (p=0.680) and the 3-year OS rates were 83% without and 90% with rituximab (p=0.542). similarly, in the RICOVER-60 trial, the 3-year EFS rates were 45% without and 50% with rituximab (p=0.593) and the 3-year OS rates were 68% without and 68% with rituximab. In a Cox regression model for event-free survival adjusted for the IPI risk factors a relevant interaction (HR 1.5; p=0.056) term between rituximab and skeletal involvement was observed. In contrast to rituximab, additive radiotherapy to sites of skeletal involvement was associated with a better outcome: 3-year EFS rates were 40% without and 75% with radiotherapy (p<0.001), 3-year OS rates were 70% without and 86% with radiotherapy to sites of skeletal involvement (p=0.064). In a multivariable analysis radiotherapy reduced the risk for an event in EFS by 70% (HR=0.3; p=0.001) and by 50% in OS (HR=0.5; p=0.111). Conclusion: Addition of rituximab failed, but radiotherapy to sites of skeletal involvement did improve the outcome of DLBCL patients with skeletal involvement. Radiotherapy to sites of skeletal involvement, though abandoned by many cooperative groups world-wide, is recommended in the rituximab era, unless prospective trials demonstrate that it might be omitted in cases with a negative PET after immunochemotherapy. Disclosures: Dreyling: Roche: Membership on an entity's Board of Directors or advisory committees. Hallek:Roche: Membership on an entity's Board of Directors or advisory committees. Schmitz:Chugai: Membership on an entity's Board of Directors or advisory committees. Pfreundschuh:Roche: Membership on an entity's Board of Directors or advisory committees; Chugai: Consultancy.

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Complete Remissions (CRs) with Azacitidine Regimens Compared to Crs with 7+3 Induction Chemotherapy and the Effect on Overall Survival

Blood ◽

10.1182/blood.v128.22.1613.1613 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1613-1613 ◽

Cited By ~ 2

Author(s):

Megan Othus ◽

Mikkael A Sekeres ◽

Sucha Nand ◽

Guillermo Garcia-Manero ◽

Frederick R. Appelbaum ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Research Funding ◽

Cox Regression ◽

Intensive Therapy ◽

Univariate Analysis ◽

Multivariable Analysis ◽

Curative Intent ◽

Kaplan Meier ◽

The Impact

Abstract Background: CR and CR with incomplete count recovery (CRi) are associated with prolonged overall survival (OS) for acute myeloid leukemia (AML) patients (pts) treated with curative-intent, induction therapy. For AML pts treated with azacitidine (AZA), response (CR, partial response, marrow CR, or hematologic improvement) is also associated with prolonged OS. We evaluate whether patients given AZA for myelodysplastic syndromes (MDS) or AML had longer OS if they achieved CR. We also compare the effect size of CR on OS between AZA regimens and 7+3. Patients and Methods: We analyzed four SWOG studies: S1117 (n=277) was a randomized Phase II study comparing AZA to AZA+lenalidomide or AZA+vorinostat for higher-risk MDS and CMML pts (median age 70 years, range 28-93); S0703 (n=133) treated AML pts not eligible for curative-intent therapy with AZA+mylotarg (median age 73 years, range 60-88). We analyzed the 7+3 arms of S0106 (n=301 were randomized to 7+3, median age 48 years, range 18-60) and S1203 (n=261 were randomized to 7+3, median age 48 years, range 19-60). CR was defined per 2003 International Working Group criteria. In S1117 CR was assessed every 16 weeks and patients remained on therapy until disease progression. In S0703, S0106, and S1203 CR was assessed following 1-2 induction cycles; patients not achieving CR (S0106) or CRi (S0703 and S1203) were removed from protocol treatment. OS was measured from date of study registration. To avoid survival by response bias, we performed landmark analyses of OS. We present results based on the study-specific landmark date that 75% of pts who eventually achieved a CR had done so (S1117 144 days, S0703 42 days, S0106 44 days, S1203 34 days). Pts who did not achieve CR by this date were analyzed with pts who never achieved CR. Pts who died or were lost to follow-up before this date were excluded from analyses. As a sensitivity analysis we also analyzed based on the 90% date; results were not materially different. Log-rank tests were used to compare survival curves and Cox regression models were used for multivariable modeling including baseline prognostic factors age, sex, performance status, white blood cell count, platelet count, marrow blast percentage, de novo disease (versus antecedent MDS or therapy-related disease), study arm (for S1117 only), and cytogenetic risk (IPSS criteria for S1117, SWOG criteria for S0703, S0106, and S1203). The following analysis considers morphologic CR only. S0106 treated CR with incomplete count recover (CRi) pts as treatment failures (S0703 and S1203 did not) and CRi was not defined for S1117. Hematologic improvement was only defined for S1117 patients. Results: In univariate analysis, CR was significantly associated with prolonged survival among MDS pts treated with azactidine on S1117 (HR=0.55, p=0.017), confirming the results seen in AML pts treated with azacitidine (and mylotarg, S0703, HR=0.60, p=0.054) and 7+3 (S0106 HR=0.44, p<0.001; S1203 HR=0.32, p<0.0001) (Figure 1). For each study this relationship remained significant in multivariable analysis controlling for baseline prognostic factors (S1117 HR=0.25, p<0.001; S0703 HR=0.64, p=0.049; S0106 HR=0.45, p<0.001; S1203 HR=0.41, p<0.001). There was no evidence that the impact of CR varied across the four cohorts (interaction p-value = 0.76). In the full cohort, the effect of CR was associated with a HR of 0.45 (Table 1). Conclusion: Adjusting for pt characteristics, achievement of morphologic CR was associated with a 60% improvement in OS, on average, compared to that seen in pts who don't achieve a CR, regardless of whether pts were treated with 7+3 or AZA containing regimens, and suggesting that value CR is similar of whether pts receive more or less "intensive" therapy for these high grade neoplasms. Support: NIH/NCI grants CA180888 and CA180819 Acknowledgment: The authors wish to gratefully acknowledge the important contributions of the late Dr. Stephen H. Petersdorf to SWOG and to study S0106. Figure 1 Kaplan-Meier plots of landmark survival by response. Figure 1. Kaplan-Meier plots of landmark survival by response. Table 1 Multivariable analysis, N=878 Table 1. Multivariable analysis, N=878 Disclosures Othus: Glycomimetics: Consultancy; Celgene: Consultancy. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees. Erba:Millennium Pharmaceuticals, Inc.: Research Funding; Amgen: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Agios: Research Funding; Gylcomimetics: Other: DSMB; Juno: Research Funding; Daiichi Sankyo: Consultancy; Sunesis: Consultancy; Pfizer: Consultancy; Ariad: Consultancy; Jannsen: Consultancy, Research Funding; Incyte: Consultancy, DSMB, Speakers Bureau; Celator: Research Funding; Astellas: Research Funding; Celgene: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau.

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Hispanic Ethnicity and the Risk of Pediatric Leukemia Relapse

Clinical Pediatrics ◽

10.1177/0009922817732147 ◽

2017 ◽

Vol 57 (6) ◽

pp. 656-659

Author(s):

Ernest K. Amankwah ◽

Greg A. Hale

Keyword(s):

Cox Regression ◽

Small Sample Size ◽

Small Sample ◽

Single Institution ◽

Relapse Free Survival ◽

Pediatric Leukemia ◽

Free Survival ◽

Hazard Ratios ◽

Leukemia Relapse ◽

Study Participants

Limited knowledge currently exists on the disparity in pediatric leukemia relapse. This study compared the risk of pediatric leukemia relapse between Hispanic and non-Hispanic Whites. Study participants were children (<20 years) diagnosed with leukemia from January 2006 to December 2014 at the Johns Hopkins All Children’s Hospital, St. Petersburg, Florida. Hazard ratios and 95% confidence intervals for relapse-free survival were calculated using adjusted Cox regression. The study included 35 Hispanic and 94 non-Hispanic Whites. Among patients <10 years old, there was a significantly higher risk of relapse in Hispanic compared to non-Hispanic Whites (hazard ratio = 6.19, 95% confidence interval = 1.15-33.27). No association was observed for patients aged ≥10 years nor all participants combined. Although the finding of this study may suggest that ethnic disparity in pediatric leukemia relapse may exist in younger children, our finding is limited by the small sample size from a single institution. Therefore, future larger multiinstitutional studies are warranted.

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Development and validation of nomograms for prediction of overall survival and cancer-specific survival of patients of colorectal cancer

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyz182 ◽

2019 ◽

Vol 50 (3) ◽

pp. 261-269

Author(s):

Jieyun Zhang ◽

Yue Yang ◽

Xiaojian Fu ◽

Weijian Guo

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Prognostic Model ◽

Cox Regression ◽

External Validation ◽

Cancer Prognosis ◽

Cancer Specific Survival ◽

Internal Validation ◽

Development And Validation

Abstract Purpose Nomograms are intuitive tools for individualized cancer prognosis. We sought to develop a clinical nomogram for prediction of overall survival and cancer-specific survival for patients with colorectal cancer. Methods Patients with colorectal cancer diagnosed between 1988 and 2006 and those who underwent surgery were retrieved from the Surveillance, Epidemiology, and End Results database and randomly divided into the training (n = 119 797) and validation (n = 119 797) cohorts. Log-rank and multivariate Cox regression analyses were used in our analysis. To find out death from other cancer causes and non-cancer causes, a competing-risks model was used, based on which we integrated these significant prognostic factors into nomograms and subjected the nomograms to bootstrap internal validation and to external validation. Results The 1-, 3-, 5- and 10-year probabilities of overall survival in patients of colorectal cancer after surgery intervention were 83.04, 65.54, 54.79 and 38.62%, respectively. The 1-, 3-, 5- and 10-year cancer-specific survival was 87.36, 73.44, 66.22 and 59.11%, respectively. Nine independent prognostic factors for overall survival and nine independent prognostic factors for cancer specific survival were included to build the nomograms. Internal and external validation CI indexes of overall survival were 0.722 and 0.721, and those of cancer-specific survival were 0.765 and 0.766, which was satisfactory. Conclusions Nomograms for prediction of overall survival and cancer-specific survival of patients with colorectal cancer. Performance of the model was excellent. This practical prognostic model may help clinicians in decision-making and design of clinical studies.

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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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Ten Year Follow up Analysis of the OSHO Phase III Trial (AML 96) Comparing Different Application Modes of AraC in Patients below 60 Years with Acute Myeloid Leukemia (AML): No Impact of AraCApplication Mode on Remission Rate, Toxicity, Disease-Free Survival or Overall Survival

Blood ◽

10.1182/blood.v112.11.2966.2966 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2966-2966

Author(s):

Cornelia Becker ◽

Rainer Krahl ◽

Antje Schulze ◽

Georg Maschmeyer ◽

Christian Junghanß ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Cox Regression ◽

Disease Free Survival ◽

Phase Iii ◽

High Dose ◽

Event Free Survival ◽

Free Survival ◽

Significant Difference

Abstract Clinical trials on different cytarabine doses for treatment of AML provide evidence of a dose response effect, but also for increase toxicity after high dose AraC (HDAC). Pharmacokinetic measurements of cytarabine-triphosphate (AraC-CTP), which is the most relevant cytotoxic metabolite of AraC, have revealed its formation in leukemic cells to be saturated with infusion rates above 250 mg/m2/h, this being significantly lower than used in HDAC schedules. Methods: Based on a pharmacological model and encouraging results of a phase II study we conducted a prospective randomized multicenter clinical trial comparing the effects of two different application modes of AraC in patients up to 60 years with untreated newly diagnosed AML. Patients were randomized to receive AraC at two different infusion rates (IR) during induction and consolidation treatment: arm A/experimental: 1 × 2 g/m2/d AraC over 8 hours (IR 250 mg/m2/h) arm B/standard: 2 × 1 g/m2/d AraC over 3 hours (IR 333 mg/m2/h). Induction and first consolidation consisted of AraC (days 1, 3, 5, 7) in combination with an anthracycline (Idarubicine 12 mg/m2 or Mitoxantrone 10 mg/m2, days 1–3). The final dosage points (AraC day 7 and anthracycline day 3) were excluded from the second consolidation. The third consolidation consisted of either allogeneic or autologous stem cell transplantation or of chemotherapy identical to second consolidation. Results: From 02/97 to 04/02 419 patients were enrolled in the study. The present analysis is based on 361 eligible and evaluable patients with a median follow up of 7 years. CR was reached in 249/361 (69%; 95%CI: 65%–74%) patients. No statistically significant differences were detected between arms A and B with regard to CR-rate (69% vs 69%) or early death rate (11% vs 8%). Hematological recovery of median white blood cell count (WBC) > 109/l and median platelets (plt) > 50 × 109/l revealed no difference between arms A and B after induction (WBC day 22 vs 22, p=0,68; plt day 25 vs 26, p=0,41) and consolidation (WBC day 28 vs 27, p=0,07; plt day 42 vs 40, p= 0,58). The event free survival (EFS) after 5 years is 0,25 ± 0,03 % for all patients with an overall survival of 0,31 ± 0,03 % after 5 years. For the purposes of analysis, the 83 transplant patients (23 allogeneic MRD, 14 allogeneic MUD and 46 autologous) were censored at time of transplant. No statistically significant difference between arms A and B in regard to EFS (0,25 ± 0,04 vs 0,25 ± 0,04, p=0,99), relapse incidence (0,63 ± 0,06 vs 0,60 ± 0,06, p=0,89), overall survival (0,32 ± 0,04 vs 0,30 ± 0,04, p=0,44) and therapy associated mortality (0,18 ± 0,04 vs 0,17 ± 0,03, p=0,95) were detectable after adjustment of prognostic factors. An analysis of risk factors by multivariate cox regression model confirmed cytogenetics at diagnosis to be the most important risk factor for CR rate (p<10−6) and for EFS (p<10−6). Other significant prognostic factors for EFS evaluated in the multivariate analysis were de novo vs secondary AML (p=0,0001), WBC (continuous) (p=0,001), LDH (>1–4 × vs other ULN) (p=0,008) and FAB classification (FAB M0,6,7 vs FAB M1,2,4,5) (p=0,0005). EFS after 5 years shows a significant correlation to cytogenetics (p<10−6) with 0,71±0,1, 0,27±0,05, 0,20±0,06 and 0,03±0,03 for favorable, normal, other and unfavorable cytogenetic karyotype, respectively. Conclusion: We conclude that the application of AraC at the presumptive saturating infusion rate of 250 mg/m2/h results in comparable remission rates, toxicity, event free survival and overall survival as compared to the standard IR with 333 mg/m2/h.

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Curative Radiotherapy using Different Radiation Techniques for Isolated Lung Metastasis from Colorectal Cancer

Tumori Journal ◽

10.1177/030089161309900112 ◽

2013 ◽

Vol 99 (1) ◽

pp. 68-75 ◽

Cited By ~ 2

Author(s):

Sunyoung Lee ◽

Dae Yong Kim ◽

Sun Young Kim ◽

Woong Sub Koom ◽

Sun Young Lee ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factors ◽

Treatment Response ◽

Surgical Resection ◽

Lung Metastasis ◽

Local Control ◽

Relapse Free Survival ◽

Free Survival ◽

Curative Radiotherapy ◽

Isolated Lung

Aims and background Surgical resection remains the mainstay for the treatment of colorectal lung metastasis, but a group of patients who are medically inoperable or unsuitable for surgery are treated with radiotherapy. The purpose of this multi-institutional study was to evaluate the clinical outcome and investigate the prognostic factors affecting local control and survival in this subset of patients. Methods We retrospectively analyzed 30 patients with 43 lesions who underwent curative radiotherapy for isolated lung metastasis from colorectal cancer at nine institutions from 2003 and 2008. A total dose of 42–75 Gy at the peripheral planning target volume was administered in 3–35 fractions. The median biologically equivalent dose was 84 Gy (range, 58.5–180). Results Treatment response was complete in 10 (33.3%), partial in 13 (43.3%), stable in six (20.0%), and progressive in one patient (3.3%). The median follow-up period for all patients was 29.0 months (range, 5.0–93.8). Kaplan-Meier local control at 5 years was 44%. The median survival was 46.2 months, and the 5-year overall survival was 47%. Twenty-three patients (77%) experienced treatment failure, most of which were intrapulmonary failure. The intrapulmonary relapse-free survival and overall relapse-free survival at 5 years were 22% and 19%, respectively. Treatment response and pre-radiotherapy carcinoembryonic antigen level were significant prognostic factors for local control and survival. Grade 3–5 toxicity occurred in 7 patients. Three patients had grade 5 toxicity, including radiation pneumonitis, a tracheoesophageal fistula, and hemoptysis. Conclusions Curative radiotherapy for isolated lung metastasis from colorectal cancer in patients who are medially inoperable or unsuitable for surgery results in long-term survival, comparable to surgical resection. Curative radiotherapy could be an effective and noninvasive alternative if dose-limiting toxicity is carefully considered, particularly in patients with bilateral or central lesions.

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