Immune checkpoint inhibitor responses in KIT-mutated metastatic melanoma.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 199-199
Author(s):  
Meredith Ann McKean ◽  
Junna Oba ◽  
Junsheng Ma ◽  
Lauren Elaine Haydu ◽  
Roland L. Bassett ◽  
...  
Keyword(s):  
Treatment Initiation ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Response To Therapy ◽  
Unknown Primary ◽  
Clinical Response Rate ◽  
Exon 2 ◽  
Kit Mutation ◽  
Exon 11

199 Background: KIT-mutated MM is a rare melanoma entity. Response rates of KIT-mutated MM to anti CTLA-4 and anti PD-1 have not previously been reported. Methods: A single-institution retrospective review identified patients (pts) with KIT-mutated MM treated with at least two doses of anti CTLA-4 or anti PD-1 between 2008-2017 with response determined by immune-related response criteria (irRC). Overall survival (OS) was from ICI start to death or last follow-up date, and progression-free-survival (PFS) was from ICI start to date of progression or death if pts deceased without disease progression. Results: Thirty-five pts treated with ipilimumab were identified. Median follow-up was 63.7 months. Median age at MM diagnosis was 65.4 years (range 26-81) and 54.3% were male. Subtypes were 51.4% mucosal, 22.9% acral-lentiginous, 22.9% cutaneous, and 2.9% unknown primary. KIT mutations were 57.1% exon 11, 25.7% exon 17, 11.4% exon 13, and 5.7% exon 2. Anatomical M stage at treatment initiation was 11.4% M1a, 34.3% M1b, and 54.3% M1c. Median OS was 11.8 months (8.4-35.6) and PFS was 3.0 months (2.8-5.8). Responses to ipilimumab were 8.6% complete response (CR), 11.4% partial response (PR), 28.6% stable disease (SD), and 51.4% progressive disease (PD) for a 48.6% clinical response rate (CRR). Twenty pts treated with anti PD-1 were identified. Median follow-up was 7.9 months. Median age at MM diagnosis was 66.7 years (range 42.6-86.8) and 70% were male. Subtypes were 40% mucosal, 30% cutaneous, 20% acral-lentiginous, and 10% unknown primary. KIT mutations were 45% exon 11, 35% exon 17, 10% exon 2, 5% exon 13 and and 5% exon 10. Anatomical M stage at treatment initiation was 10% M1a, 15% M1b, and 75% M1c. Median OS was 22.5 months (7.4-NA ) and PFS was 3.2 months (2.7-NA). Responses to anti PD-1 were 10.0% CR, 25.0% PR, 20.0% SD, and 45.0% PD for a 55.0% CRR. For both anti CTLA-4 and anti PD-1 treated cohorts, univariate analysis demonstrated no statistical significance between tumor response to ICI and clinical pt characteristics or KIT mutation exon. Conclusions: KIT-mutated MM demonstrated CRR of 48.6-55.0% to ICI. There was no correlation between pt characteristics or KIT exon mutation and response to therapy; however, analysis was limited by sample size.

scholarly journals Delay to initiate treatment is associated with unsuccessful treatment outcome among new pulmonary tuberculosis patients in Tigray, Northern Ethiopia: a follow up study

2021 ◽  
Author(s):  
kiros Tedla ◽  
Girmay Medhin ◽  
Gebretsadik Berhe ◽  
Afework Mulugeta ◽  
Nega Berhe
Keyword(s):  
Treatment Outcome ◽  
Pulmonary Tuberculosis ◽  
Treatment Outcomes ◽  
Treatment Initiation ◽  
Statistical Significance ◽  
Northern Ethiopia ◽  
Follow Up Study ◽  
Unsuccessful Treatment ◽  
Increased Risk

Abstract Background : Previous studies in Ethiopia indicated that tuberculosis (TB) patient’s elapse long time before treatment initiation. However, there is very limited evidence on the association of delay to initiate treatment with treatment outcome. Objective : To investigate the association of time to treatment initiation delay with treatment outcomes of new adult TB patients in Tigray region of Ethiopia. Methods : We conducted a follow up study from October 2018 to April 2020 by recruiting 875 newly diagnosed Pulmonary Tuberculosis (PTB) patients from 21 randomly selected health facilities. Study participants were selected using simple random sampling technique during treatment initiation from October 1/2018 to October 30/2019. Delay to initiate treatment and treatment outcome were collected using standardized questionnaire and laboratory investigation. Adherence of TB patients to their treatment was collected using a 10 points linear visual analogue scale (VAS) at the end of treatment. The association of delay to initiate treatment with treatment outcome was modeled using log binomial regression model. Statistical significance was reported whenever p-value was less than 0.05. Data was analyzed using SPSS software version 21. Result : The median total delay to treatment initiation was 62 days with inter-quartile range of 16-221 days. A unite increase in a day to initiate treatment results in increment of risk of unsuccessful treatment outcome by 2.3. Other factors associated with unsuccessful treatment outcomes were being less adherent to the treatment, HIV co infection, being smear positive at initiation of treatment and after 2 months of treatment initiation. Conclusion : delay in a day to initiate treatment is associated with increased risk of unsuccessful treatment outcome. Any effort targeted towards reducing the negative effects of PTB should target on strategies that reduces the length of delay to initiate treatment and strengthen community engagement to improve treatment adherence of patients that have started treatment.

A Retrospective Hospital Based Study of 440 Patients of Aplastic Anemia from India: Epidemiology; Response to Therapy; and Possible Significance of Jaundice during Therapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5299-5299 ◽  
Author(s):  
Rajat Kumar ◽  
Dharma R. Choudhary ◽  
Manoranjan Mahapatra ◽  
Atul Kotwal ◽  
Alka Mathur ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Statistical Significance ◽  
Medical Science ◽  
Specific Treatment ◽  
Complete Response ◽  
Response To Therapy ◽  
Acute Leukemias ◽  
Overall Response ◽  
High Incidence

Abstract All new cases of aplastic anemia (AA) seen in the Hematology out patient department (OPD) of All India Institute of Medical Science (AIIMS) from January 2001 to December 2003 were studied till last follow up. Complete response (CR) was defined as - normalization of blood counts; Partial response (PR) as - improvement in blood counts, transfusion independence and not meeting criteria of CR. Database was created in MS Access and SPSS ver 11 was used for statistical analysis. Descriptive statistics were calculated and appropriate tests of significance carried out. Result- A total of 440 cases of AA were seen during the study period. The total number of new hematology patients seen in the same period was 8605; thus AA comprised 51.13 per thousand (95% CI, 37.9–67.1) new hematology cases. The number of acute leukemias (AML and ALL) diagnosed during this period was 392: the ratio of AA to acute leukemia was 1.1:1. The total number of OPD patients registered in AIIMS for these 3 years was 43,04,849. Thus AA patients comprised 102.23 per million (95% CI, 83.2–123.8) hospital OPD patients. This very high incidence of AA may be due to the tertiary nature of AIIMS. The median age at presentation was 19yr (range 2–84), with males 311 (71%) and females 129 (29%). At presentation the hematological values were: mean hemoglobin (Hb) 5.2 ± 2.03 g/dl; mean total leucocyte count (TLC) 3.1 ± 1.3 x 109/L, mean platelet counts 33.8 ± 19.5 x 109/L. Follow up period was for a median of 3 months (range 0–42). Specific treatment consisted of (a) Androgens - Stanozolol at 2 mg/kg/d (b) Cyclosporine at 3mg/kg/d (c) Antithymocyte globulin at total dose of 75–80mg/kg over 5 to 8 days and (d) combinations of these drugs. The following subgroups were excluded from analysis (i) 14 (3.1%) patients whose records were incomplete and (ii) 38 (8.6%) patients who received only supportive therapy with no response, but whose individual follow up was limited. The overall response to all therapies was 29.7%. The response to different subgroups and statistical significance is given in Table. Jaundice occurred in 23 (5.2%) patients during treatment and HBsAg was positive in two. The course of jaundice was clinically uncomplicated and lasted for 2 to 3 weeks. An interesting finding was a partial or complete response to therapy in 19/23 (82.6%) with CR in 47.8% and PR in 34.8%. The difference in response rate of those who developed jaundice while on therapy and those who did not was statistically significant (P=0.000). Conclusions: The high incidence of AA in India provides a potential for future studies regarding its etiopathogenesis and therapy. Economic limitations make Stanozolol an important drug in developing countries with its response rates of 19.7%. The unexpected high response in those who developed jaundice during therapy suggests that this could be a marker for recovery. Response§ to Different Therapies in 388 Patients of Aplastic Anemia Treatment group Androgen alone Cyclosporin alone Androgen and Cyclosporin ATG + Cyclosporin ±Androgen Test Chi square test. ©Not statistically significant. ®Statistically significant. §Response compared to overall response to other therapies. Total number (%) 172 (39.1) 13 (3) 179 (40.7) 24 (6.3) Overall response, % 19.7 8.3 31.2 62.5 PR, % 8.6 8.3 15.9 33.3 CR, % 11.1 0 15.3 29.2 P value 0.067© not done 0.083© 0.000®

Gene Mutations and Minimal Residual Disease (MRD) As Predictors of Remission Duration in Adults with Core Binding Factor (CBF) Acute Myeloid Leukemia (AML) Treated with High-Dose Cytarabine (HDAC) - First Results of the Prospective French Intergroup CBF-2006 Trial

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 410-410
Author(s):  
Eric Jourdan ◽  
Nicolas Boissel ◽  
Odile Blanchet ◽  
Aline Renneville ◽  
Christian Recher ◽  
...  
Keyword(s):  
Fusion Gene ◽  
Univariate Analysis ◽  
Gene Mutations ◽  
Response To Therapy ◽  
High Dose ◽  
Gene Transcript ◽  
Kit Mutation ◽  
Ras Mutations ◽  
Remission Duration ◽  
Log Ratio

Abstract Abstract 410 Background. CBF-AML is a favorable AML subset cytogenetically defined by t(8;21) or inv(16)/t(16;16) rearrangements, respectively responsible for RUNX1-RUNX1T1 (CBFa) or CBFB-MYH11 (CBFb) gene fusion. Nonetheless, relapse incidence may reach 30–40% in these patients. Even if not yet prospectively validated, early MRD monitoring based on chimeric fusion gene transcript quantification by RQ-PCR may help to define patients at higher risk of relapse. Detection of activating KIT and FLT3 gene mutations has also been retrospectively associated with higher relapse rate in these patients. The French CBF-2006 trial (NCT00428558) aimed to prospectively evaluate both markers as predictors of remission duration in homogeneously treated patients. Methods. Patients (18–60y) with newly diagnosed CBF-AML were eligible. All were studied for KIT exon 8/17, FLT3-ITD, FLT3-D835, N-RAS and K-RAS mutations. They were randomized to receive timed-sequential or standard induction. Timed-sequential induction was cytarabine (AraC) 500 mg/m2 CI D1-3 and daunorubicine (DNR) 60 mg/m2 D1-3, followed by AraC 1 g/m2/12h D8-10 and DNR 35 mg/m2 D8-9. Standard arm was AraC 200 mg/m2 CI D1-7 and DNR 60 mg/m2 D1-3, followed by the second sequence at D16-18 only in case of persistent bone marrow (BM) blasts at D15. Patients in first complete remission (CR1) received 3 HDAC consolidation cycles with AraC 3 g/m2/12h D1/3/5. Fusion gene expression was quantified at baseline and before each HDAC cycle (MRD1, MRD2, MRD3) by the 100 × fusion gene/cABL ratio. Patients not reaching a 3-Log ratio reduction at MRD2 were offered allogeneic stem cell transplantation (SCT) in CR1 if they had an HLA-identical donor or could enter a single-agent dasatinib sub-study (see Boissel et al., this meeting). Results. Among the planned 200 patients randomized, 198 met eligibility criteria (96 CBFa and 102 CBFb, compared in Table 1). Overall, incidences of KIT, RAS, FLT3-D835 and FLT3-ITD mutations were 21%, 29%, 10% and 6%, respectively. Patients with KIT and FLT3-D835 mutations had higher WBC (P=0.04 and 0.02) and BM blast percentage (P=0.0004 and 0.05). Those with RAS mutations had lower BM blast percentage (P=0.01) and baseline transcript ratio (P=0.001). Overall, 196 patients reached CR1 and 55 relapsed. At 3 years, probabilities of durable remission, disease-free (DFS) and overall survival from CR were 64%, 61% and 84%, respectively, without differences between the CBF subsets or induction arms. Fifty-five patients did not reach the 3-Log MRD2 reduction (18 CBFa and 37 CBFb, P=0.006), 9 receiving SCT in CR1. Poor MRD2 response correlated with age (P=0.01), WBC (P=0.04), KIT mutations (P=0.04), and initial transcript ratio (P=0.004). Among the characteristics listed in Table 1, shorter remission duration was associated with high WBC (P=0.011), high BM blast percentage (P=0.062), del(9q) (P=0.041), KIT mutation (P=0.048), FLT3-D835 mutation (P=0.077), high initial transcript ratio (P=0.053), and <3-Log MRD2 reduction (P=0.006) in univariate analysis stratified by CBF subtype and treatment arm. In multivariate analysis, the three latter factors, but not KIT mutations, remained independently predictive of shorter remission duration and DFS (P= 0.014, 0.033, 0.002 and 0.001, 0.012, 0.005, respectively). Censoring patients receiving SCT in CR1 yielded similar results. Conclusions. This prospective study of 198 CBF-AML patients homogeneously treated with HDAC revealed significant correlations between initial characteristics and response to therapy. Prognostic analysis did not find that KIT mutations had independent impact on outcome, which was rather influenced by baseline fusion transcript ratio and post-consolidation MRD reduction (reminiscent of Schnittger et al. 2003), and FLT3-D835 mutation. Ongoing pan-genomic analyses might help to further dissect CBF-AML heterogeneity. Disclosures: No relevant conflicts of interest to declare.

Survival of Newly Diagnosed T-Cell Lymphoma (TCL) in the Modern Era: Investigation of Prognostic Factors with Critical Examination of Therapy in a Multicenter US Cohort.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2728-2728
Author(s):  
Andrew M. Evens ◽  
Tatyana Feldman ◽  
Aimee Kroll ◽  
Lori S. Muffly ◽  
Eric Winer ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
T Cell ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
Response To Therapy ◽  
Critical Examination ◽  
Newly Diagnosed ◽  
Stage Disease

Abstract Abstract 2728 Background: TCLs are uncommon malignancies consisting of heterogeneous pathologic subtypes and outcomes. Despite development of prognostic models, there is little data of outcomes in large cohorts examining the impact of frontline therapy and the role of consolidative stem cell transplantation (SCT). Methods: We performed a multi-center retrospective analysis of a large cohort of newly diagnosed mature TCLs (non-cutaneous) from 2000–2010 across 9 U.S. academic centers. We examined detailed information regarding patient characteristics and treatment(s) received. Further, we determined prognostic factors for associations with survival in univariate analysis and multivariate Cox regression proportional models. Results: Among 402 cases of mature TCL, 341 had complete treatment and follow-up data. This included 107 cases of peripheral TCL (PTCL NOS), 89 anaplastic large cell lymphoma (ALCL), 77 angioimmunoblastic TCL (AITL), 23 NK/TCL, 20 acute t-cell leukemia/lymphoma (ATLL), 10 enteropathy-associated TCL (EATCL), 7 subcutaneous panniculitis-like TCL (SCPTCL), 5 hepatosplenic TCL (HSL), and 4 transformed CTCL (t-CTCL) cases. 60% of pts were men and the median age was 62 years (range 18–95). At initial diagnosis, performance status was 2–4 in 36%, B symptoms in 47%, elevated LDH in 55%, anemia in 64%, and hypoalbuminemia in 46% at baseline. 74% of pts had advanced-stage disease, 29% had bone marrow involvement, 52% had other (non-marrow) extranodal sites, and only 9% had bulky disease >7cm. Twenty-three pts received only palliative therapy all of whom survived <3.5 months. Among the remaining 318 pts, CHOP-like therapy was the most common initial regimen (74%; 5% of which included etoposide), 7% hyperCVAD/MA, 3% EPOCH, 2% CMED, 2% gemcitabine-based, 2% ifosfamide-based, and 10% other. 21% received radiation therapy (RT) as part of initial treatment, while 34 pts (11%) received a SCT in 1st remission (85% autologous). Overall response to therapy was 73% (61% complete), while 24% had primary refractory disease. With a median follow-up of 38 months (6–109), 3-year progression-free survival (PFS) and overall survival (OS) for all pts were 32% and 52%, respectively (Figure). Factors predictive of outcome by univariate analysis are detailed in the Table (includes differential survival by WHO subtype and PIT and IPI). On multivariable regression analysis of pre-treatment factors, only Ann Arbor stage I/II remained significant (PFS: HR 0.59 [95%CI 0.38–0.93], p=0.023); and OS: HR 0.46 [95%CI 0.25–0.85], p=0.013). Regarding induction treatment, the only impact based on regimens received were inferior outcomes with CMED or EPOCH therapy; these findings persisted on multivariate analysis. The addition of etoposide to CHOP did not appear to impact outcome, although those numbers were small. Notably, consolidative SCT portended significantly improved survival on multivariate analysis when controlling for gender, LDH, albumin, and stage (PFS: HR 0.46 [95%CI 0.24–0.89], p=0.02; and OS: 0.43 [95%CI 0.19–0.99], p=0.04), but this did not reach significance when adjusting for response to 1st therapy (PFS: HR 0.55 [95%CI 0.28–1.08], p=0.08; OS: HR 0.47 [95%CI 0.17–1.29], p=0.14). Conclusions: In this large US cohort of TCL, response, PFS, and OS compared favorably with historical controls. Further, we documented that NK/TCL, AITL, and ALCL (ALK+ and negative) were all associated with improved OS vs PTCL NOS. On multivariable analysis, limited-stage disease was the predominant predictive factor for survival. Additionally, consolidative SCT was associated with improved PFS and OS, however this benefit appeared to be nullified after controlling for initial response. Disclosures: No relevant conflicts of interest to declare.

Analysis of Transfusion Dependency Development and Disease Evolution in Patients with MDS with 5q- and without Transfusion Needs at Diagnosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3180-3180
Author(s):  
Felix Lopez-Cadenas ◽  
Blanca Xicoy ◽  
Silvia Rojas P ◽  
Kaivers Jennifer ◽  
Ulrich Germing ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Board Of Directors ◽  
Research Funding ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Rank Test ◽  
Advisory Committees ◽  
Disease Evolution ◽  
Free Survival

Abstract Introduction: Myelodysplastic syndrome with del5q (MDSdel5q) is the only cytogenetically defined MDS category recognized by WHO in 2001, 2008 and 2016 and is defined as a MDS with deletion on the long arm of chromosome 5 and less than 5% of blast cells in bone marrow. It is known that for patients with MDSdel5q and transfusion dependence (TD), Len (LEN) is the first choice of treatment. However, data regarding factors that may impact on the development of TD or disease evolution in patients diagnosed without TD are scanty. In our study a retrospective multicenter analysis on patients with low-int 1 MDSdel5q without TD at diagnosis has been performed in order to answer these questions. Patients and methods: We performed a multicenter collaborative research from the Spanish (RESMD) and German MDS registries. Data from 153 low risk MDSdel5q without TD at diagnosis were retrospectively analyzed. Statistical analysis: Data were summarized using median, range, and percentage. The event of TD was defined as the development of TD according to the IWG criteria (2006) and/or the beginning of a treatment which could modify disease course (LEN or ESA). Transfusion or treatment free survival (TFS), overall survival (OS) and leukemia free survival (LFS) were measured from diagnosis to TD or treatment, the first occurred (or to last follow up if none), last follow up or death from any cause and evolution to AML, respectively. TFS, OS and LFS were analyzed using the Kaplan Ð Meier method. The Log-rank test was used to compare variables and their impact on survival for univariate analysis.Multivariate analysis was performed using Cox's proportional hazards regression model. For comparison of Kaplan Meier curves the long rank test was used, with statistical significance with p<0.05. Statistical analysis was performed using SPSS 20.0. Results: Main clinical and biological characteristics were summarizing in table 1. From the total of 153 patients, finally 121 were evaluable. During the study 56 patients (46.2%) became in TD and 47 (38.8%) did not develop TD but received a modified disease course treatment. In this sense, most of the patients developed relevant anemia regarding those data (103 out of 121 patients, 85%). Median time to TD or treatment (TFS) was 20 months (1-132) from diagnosis. Secondary MDS (p=0.02), thrombocytosis (>350 109/L) (p=0.007), and neutropenia (<1.5 x 109/L) (p=0.02) were associated with poorer TFS. Thrombocytosis and neutropenia retained statistical significance in the multivariate analysis (Table 2). Among the TD patients (N=56), 42 (75%) received treatment: 28 LEN, 7 ESA and 7 other treatments. Among patients that did not develop TD (N=65), 47 (72.3%) received treatment before TD development: 16 LEN, 28 ESA and 3 other treatments. In order to know the evolution of these patients, survival analysis was performed. Median follow up was 58.9 months among alive patients and 57% of them were alive at the time of the last follow up. Estimated OS at 2 and 5 years was 94% and 64%. Regarding Univariate analysis, platelet <100 x 109/L (p=0.03), patients older than 71 years (p=0.001), and progression into AML (p=0.02) were associated with poorer OS. On the contrary, patients who had received treatment showed better OS (p<0.0001). This benefit is more evident among patients receiving LEN, median OS for patients receiving LEN, ESA/other treatments and not treated group was 137 months (CI 95%: 59,4 -215,5), 99,3 months (CI 95%: 46,6 -152) and 57,9 months (CI 95%: 38,2 -77,6), respectively, p<0.0001 (Figure 1). In the multivariate analysis, patients older than 71 years and LEN treatment retained the statistical significant impact on OS (Table 2). Twenty-eight patients (23%) progressed into AML, median time to AML was 35 months (5-122). When univariate analysis was performed, variables with adverse impact on LFS were platelets <100 x 109/L(p=0.019), neutropenia < 0.8 x 109/L (p=0.026), an additional cytogenetic abnormality (p=0.013) while treatment with LEN had a favorable impact (p=0.035). In the multivariate analysis only the presence of additional cytogenetic abnormalities retained statistical significance (Table 2). CONCLUSIONS: Most of the patients with low risk del(5q) MDS and no TD at diagnosis developed symptomatic anemia very early after diagnosis (20 months). Carefully monitoring should be stablished in order to detect this time point. Outcome of this subset of patients could improve after target therapy. Figure 1 Figure 1. Disclosures Del Cañizo: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; janssen: Research Funding; Astex: Membership on an entity's Board of Directors or advisory committees. Díez Campelo:celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Research Funding; Astex: Membership on an entity's Board of Directors or advisory committees.

Preoperative uracil/tegafur and concomitant radiotherapy in locally advanced rectal (LAR) cancer: Updated results with a median follow-up of 5 years and analysis of prognostic factors (PF)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3573-3573 ◽  
Author(s):  
C. Fernandez-Martos ◽  
I. Romero ◽  
J. Aparicio ◽  
C. Bosch ◽  
R. Girones ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Residual Disease ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Complete Information ◽  
Risk Groups ◽  
Attractive Alternative

3573 Background: Preop chemoradiotherapy (CRT) with CI 5-FU is a standard of care for LAR cancer. Oral fluoropyrimidines, an attractive alternative to intravenous 5-FU, are perceived by patients as more convenient. Methods: We performed a phase II study in patients with potentially resectable tumors, localized in middle or distal rectum, ultrasonographically staged as T3 or T4 or N+ who were treated with UFT (400 mg/m2/d, 5 days a week for 5 weeks) and concomitant RT to the pelvis (45 Gy; 1.8 Gy/d over 5 weeks). Pts underwent surgery 5 to 6 weeks later followed by four cycles of 5-FU/LV (Mayo Clinic Scheme). Early end points of efficacy (pCR, downstaging, sphincter preserving surgery) and toxicity have already been reported (JCO 2004;22:3016). We now present data on secondary objectives (RFS, DFS and OS) and univariate and multivariate analysis of clinical and pathological PF. Results: 94 patients were included and complete information on 88 (94%) is availablewith a median follow-up of 5 years (60.4 months). Actuarial Kaplan-Meier DFS, RFS and OS are 61%, 66%, and 70 %. Patterns of failure are 7% pelvic and 25% distant. Univariate analysis results are shown in the table . Survival rate was also higher among patients with no or few residual disease after CRT but did not reach statistical significance. In Cox multivariate analysis both ypT and ypN are independent PF for DFS and RFS but only ypT is an independent PF for OS. Conclusions: This approach with preop UFT/RT reproduces the results that have been accomplished with 5-FU. ypT and ypN could be helpful to identify different risk groups and to select adjuvant treatments. [Table: see text] No significant financial relationships to disclose.

Analysis of prognostic factors after 16 years of follow-up in a randomized phase II trial of neoadjuvant FAC compared with CMF in stage III breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11118-11118
Author(s):  
Julieta Leone ◽  
Jose Pablo Leone ◽  
Carlos Teodoro Vallejo ◽  
Juan Eduardo Perez ◽  
Alberto Omar Romero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Stage Iii Breast Cancer

11118 Background: Neoadjuvant chemotherapy is a standard treatment in stage III breast cancer. Prognostic factors can help to identify patients (pts) with high risk of recurrence. The aim of this study was to assess several prognostic factors after a long follow-up, in stage III breast cancer pts, treated with neoadjuvant chemotherapy. Methods: We evaluated 126 pts with stage III breast cancer that participated in a phase-II randomized trial of neoadjuvant 5-fluorouracil, doxorubicin and cyclophosphamide (FAC every 21 days) compared with cyclophosphamide, methotrexate and 5-fluorouracil (CMF days 1 and 8 every 28). Chemotherapy was administered for three cycles prior to definitive surgery and radiotherapy, and then for six cycles as adjuvant. Response was assessed by WHO criteria. Results: The median age was 52 years (range 24-75). Median follow-up was 4.5 years (range 0.2-16.4), disease free survival (DFS) 4.8 years and overall survival (OS) 6.4 years. Results of the phase-II study showed no difference in efficacy between groups. Univariate analysis showed that the number of pathologically involved lymph nodes (pLN), pathologic response and estrogen and progesterone receptor status correlated with DFS and OS. Number of pLN was the only prognostic factor with statistical significance in Cox regression test for both, DFS and OS (P=0.0004 and P=0.0006, respectively). In a subgroup analysis of pts with pLN, we found no difference in survival when we compared FAC with CMF. Conclusions: The prolonged follow-up of this study provides a unique opportunity to evaluate factors that predict long-term outcomes. After 16 years of follow-up, the number of pLN remains the most powerful predictor of survival. The subset of pts with pLN had similar survival regardless of the regimen used. Clinical trial information: NCT00002696.

Clinical and pathologic prognostic factors in adult granulosa cell tumors of the ovary

2008 ◽  
Vol 18 (5) ◽  
pp. 929-933 ◽  
Author(s):  
R. Ranganath ◽  
V. Sridevi ◽  
S. S. Shirley ◽  
V. Shantha
Keyword(s):  
Prognostic Factors ◽  
Granulosa Cell ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Optimal Cytoreduction ◽  
Free Survival ◽  
Nuclear Atypia ◽  
Granulosa Cell Tumors

The objective of this study was to determine the clinicopathologic prognostic factors in adult granulosa cell tumors of the ovary. A retrospective review of the records of patients of granulosa tumors who were treated at our institute over a period of 10 years (1995–2005) was done. Clinical, pathologic, and follow-up data were collected. A total of 34 patients who were treated during this period were subjected to analysis. Cox univariate analysis and Wilcoxon's test for multivariate analysis were used as part of the SPSS software for examining the data. It was found that optimal cytoreduction (P= 0.02), presence of nuclear atypia (P< 0.001), and increased mitoses (P= 0.03) were the three factors that impacted significantly on survival. Age, stage of the tumor, parity, and size of the tumor had no significant effect on survival. Patients who received chemotherapy had a better median disease-free survival than those who did not (60 vs 48 months), but this did not reach statistical significance (P= 0.08). Optimal cytoreduction, nuclear atypia, and increased mitoses are the statistically significant prognostic factors and may be used for selecting patients for adjuvant therapy.

scholarly journals BRAF, C-KIT, and NRAS mutations correlated with different clinicopathological features: an analysis of 691 melanoma patients from a single center

2021 ◽  
Author(s):  
Min Ren ◽  
Jing Zhang ◽  
Yunyi Kong ◽  
Yong Chen ◽  
Qianming Bai ◽  
...  
Keyword(s):  
Braf Mutation ◽  
Statistical Significance ◽  
Gene Mutations ◽  
Clinicopathological Features ◽  
Similar Distribution ◽  
Nras Mutation ◽  
Exon 2 ◽  
Kit Mutation ◽  
Metastatic Lesions ◽  
Melanoma Patients

Abstract Aims To analyze the prevalence and relevance of pathogenetic mutations in BRAF, C-KIT, and NRAS in Chinese melanoma patients to provide some potential reference for the targeted treatment in China. Methods We described the frequency and distribution of BRAF, NRAS, and C-KIT mutation in 691 melanoma patients, and analyze the statistical significance of different gene mutation with clinicopathological features. Results BRAF mutation was found in 166 patients (24.0%), and V600E was the prominent genetic alteration (87.3%). Statistical analysis showed that younger patients had a higher BRAF mutation rate than the older. Furthermore, the frequency of BRAF mutation in patients with extremity location, ALM type, thinner thickness and no ulceration was more likely to be lower. The rate of NRAS mutation was 12.6% (38/302), mainly involved codon 61 in exon 3 and codon 12 in exon 2. C-KIT mutation was detected in 65 patients (9.4%), and the most common sites of mutations was L576 in exon 11 (44.6%). Patients with NRAS or C-KIT mutation had higher Clark level and more likely to be located in extremity than those without mutation. The concordance of BRAF, NRAS, and C-KIT mutations between paired primary and metastatic lesions was 89.6% (60/67), and visceral metastases showed a highest similar distribution of gene mutations versus primary melanomas compared with lymph nodes and cutaneous metastases. Conclusions In this large cohort on Chinese population, the frequency of BRAF and NRAS mutation was relatively lower than that in Caucasian, but the clinicopathological features of BRAF, C-KIT and NRAS mutation were similar. Paired primary and metastatic lesions showed high concordance of gene mutations.

scholarly journals Catestatin as a New Prognostic Marker in Stable Patients with Heart Failure with Reduced Ejection Fraction in Two-Year Follow-Up

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Łukasz Wołowiec ◽  
Daniel Rogowicz ◽  
Joanna Banach ◽  
Wojciech Gilewski ◽  
Władysław Sinkiewicz ◽  
...  
Keyword(s):  
Troponin T ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Plasma Concentrations ◽  
Physical Exertion ◽  
Composite Endpoint ◽  
Control Group ◽  
Reduced Ejection Fraction ◽  
Before And After

Background and Purpose. The main goal of the study was to assess the usefulness of plasma concentrations of catestatin as a predictor of a composite endpoint (CE): unplanned hospitalization and death for all causes in patients with HFrEF in the midterm follow-up. Experimental Approach. The study group consisted of 52 Caucasian patients in NYHA classes II and III. The control group consisted of 24 healthy volunteers. The biomarkers, whose concentration was assessed before and after physical exertion as well as the variability of their concentration under the influence of the physical exertion, were NT-proBNP, troponin T, and catestatin. Key Results. During the 24-month follow-up period, 11 endpoints were recorded. The univariate analysis of the Cox proportional hazard model showed a statistically significant effect of all assessed CST concentrations on the occurrence of CE. In the 24-month follow-up, where the starting concentration of catestatin was compared with other recognized prognostic factors in HF, the initial concentration of catestatin showed statistical significance in CE prognosis as the only parameter tested. Conclusions. Plasma concentration of catestatin before and after physical exertion is a valuable prognostic parameter in predicting death from all causes and unplanned hospitalization in the group of patients with HFrEF in the 2-year follow-up.

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