Clinical significance of prophylactic intrathecal chemotherapy in the treatment of glioblastoma multiforme

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13022-e13022
Author(s):  
T. Iuchi ◽  
K. Hatano ◽  
T. Sakaida ◽  
S. Hirono
Keyword(s):  
Clinical Significance ◽  
Local Control ◽  
Progression Free Survival ◽  
Intrathecal Administration ◽  
High Dose ◽  
Free Survival ◽  
Local Progression ◽  
Group A ◽  
Group B ◽  
Group D

e13022 Backgrounds: We previously have reported that hypo-fractionated high-dose irradiation (HdI; 68Gy/8F) showed excellent local control but no effect on prevention of cerebrospinal fluid dissemination (CSFd), resulted in limited efficacy on patients’ survival in glioblastoma (GBM). The aim of present analysis is to evaluate the clinical significance of prophylactic intrathecal administration of thiotepa (iT) in the treatment of GBM patients. Methods: Histologically confirmed GBMs without CSFd at diagnosis were enrolled. Patients were classified into four groups owing to the post-surgical treatment strategy as follows: Group A patients (n = 65) were treated by conventional radiotherapy (cRT; 60Gy/30F) alone; Group B patients (n = 17) were by cRT concurrent witn iT; Group C patients (n = 28) were by HdI alone; Group D patients (n = 30) were by HdI concurrent with iT. In Group B and D, Ommaya reservoir was placed into the lateral ventricle and 10mg of thiotepa was administrated weekly after surgery for five times. The local progression-free survival (PFS), CSFd-free survival (CFS), and overall survival (OS) were compared in these four groups. Results: Group C and D patients showed significantly longer PFS than Group A and B (p < 0.0001), suggesting the clinical significance of HdI for local control of this tumor. On the other hand, CFS in Group B and D was significantly longer than that in Group A and C (p = 0.049), demonstrating the effect of iT for prevention of CSFd. However, significant improvement of OS on the conventional treatment (Group A, median OS: 12.3 months) was observed only in Group D (median OS: 30.2 months, p = 0.002) and not in Group B or C (24 months, p = 0.135, and 14.9 months, p = 0.481 respectively). Conclusions: These data indicated that both of local control and prevention of CSFd were required for better survival of patients with GBM, and iT concurrent with HdI may be one of the treatments that fill these requirements. No significant financial relationships to disclose.

scholarly journals Lenalidomide in Combination with Standard R-CHOP Overcomes the Negative Prognostic Value of Peripheral Blood Absolute Lymphocyte/Monocyte Ratio at Diagnosis and during Treatment in Patients with Diffuse Large B-Cell Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4139-4139
Author(s):  
Alessia Castellino ◽  
Levy D. Pederson ◽  
Kay M. Ristow ◽  
Christina Stenzel ◽  
Betsy Laplant ◽  
...  
Keyword(s):  
Treatment Group ◽  
Tumor Microenvironment ◽  
Prognostic Value ◽  
De Novo ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Free Survival ◽  
Group A ◽  
Group B ◽  
Group D

Abstract Introduction. The peripheral blood absolute lymphocyte (ALC)/monocyte (AMC) ratio (ALC/AMC), as a surrogate of host immunity (i.e. ALC) and tumor microenvironment (i.e. AMC), is a predictive biomarker for clinical outcomes in diffuse large B-cell (DLBCL) patients. An ALC/AMC ratio ≥ 1.1 has been shown to be predictive of better survival both at baseline and during each therapy cycle in patients treated with R-CHOP [Porrata et al, 2014]. Lenalidomide is an immunomodulatory drug, effective in DLBCL patients, with various mechanisms of actions on the tumor microenvironment and the host immune response. In this study we analyze the prognostic value of ALC/AMC ratio in a cohort of newly diagnosed DLBCL patients treated with Lenalidomide plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, R2-CHOP) in a phase II trial (MC078E trial, [Nowakowski et al, 2015]). Methods. All patients with de-novo DLBCL enrolled in the phase II trial MC078E and treated at diagnosis with R2-CHOP regimen were included in the analysis. We investigated the ALC/AMC ratio at baseline and each R2-CHOP cycle as predictor of progression-free survival (PFS) and overall survival (OS). The ALC/AMC ratio was obtained by dividing the ALC by the AMC from the automated white blood cell differential obtained from the complete blood cell count on day 0 of each treatment cycle (range from day -3 to day 0 of each course). Patients were then divided in 4 groups on the basis of pattern of ALC/AMC ratio during treatment: group A: patients with ALC/AMC ratio ≥ 1.1 throughout all cycles; group B: patients with ALC/AMC ratio ≥ 1.1 at baseline, but then obtained an ALC/AMC < 1.1 during treatment; group C: patients with ALC/AMC ratio < 1.1 at baseline, but then gained an ALC/AMC ≥ 1.1 during treatment; group D: patients with ALC/AMC ratio < 1.1 throughout all cycles. PFS and OS were analyzed in the different groups. We separately conducted the same analysis in a matched control cohort of 94 DLBCL patients from the Mayo Clinic Lymphoma Database treated with standard R-CHOP. Results. A total of 63 patients with de-novo DLBCL treated with R2CHOP regimen at diagnosis were included in the analysis. Clinical characteristics were: median age 67 years (22-87), male sex 61.9%, III-IV advance stage 87.3%, elevated LDH serum levels 66.7%, intermediate-high/high International Prognostic index (IPI) score in 54% cases. No differences in 3y-PFS and 3y-OS in patients with ALC/AMC ratio ≥ 1.1 vs ALC/AMC < 1.1 at baseline and at each R2-CHOP course have been observed. In a landmark analysis from day 0 of the last cycle, 3y-PFS in group A vs B vs C vs D was: 71.4% vs 67.1% vs 66.7% vs 85.7%, respectively (p 0.80); 3y-OS in group A vs B vs C vs D was: 85.7% vs 86.5% vs 66.7% vs 100%, respectively (p 0.74). No differences in both 3y-PFS and 3y-OS were observed comparing group A vs B, in group C vs D, and in group A vs D. Unlike what was observed in the R-CHOP treated DLBCL patients, in a univariate analysis ALC/AMC < 1.1 during all cycles of R2CHOP was not a predictor for inferior outcomes (Figure 1.a). In the matched cohort of patients treated with standard R-CHOP, ALC/AMC < 1.1 at baseline and at each course demonstrated to be predictive of worse outcome (p <0.01),survival was significantly different in the 4 groups identified according to ALC/AMC ratio during treatment and ALC/AMC < 1.1 maintained during all cycles of R2CHOP was predictive of worse PFS and OS (Figure 1.b). Conclusions. Lenalidomide in combination with standard R-CHOP (R2-CHOP), in previously untreated DLBCL patients, appears to overcome the negative prognostic value of ALC/AMC ratio observed in patients treated with R-CHOP alone. This could reflect the additional effect of lenalidomide to standard therapy on tumor microenvironment and on host immunity response. Figure 1: Landmark Analysis for Progression Free Survival and Overall Survival by ALC/AMC groups within R2CHOP (1.A) and R-CHOP (1.B). Group A: ALC/AMC >=1.1 for all cycles; Group B: ALC/AMC >=1.1 at baseline and obtained <1.1 during treatment; Group C: ALC/AMC <1.1 at baseline and obtained >=1.1 during treatment; Group D: ALC/AMC <1.1 for all cycles. Disclosures Witzig: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Does High Dose Cytosine Arabinoside Improves Disease Free Survival for Down Syndrome Acute Myelocytic Leukemia Patients?.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4612-4612
Author(s):  
Mahasen Saleh ◽  
Ashraf Khairy ◽  
Mohammed Al-Mahr ◽  
Hassan El-Solh ◽  
AbdulRahman Al-Musa ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Disease Free Survival ◽  
High Dose ◽  
Acute Myelocytic Leukemia ◽  
Free Survival ◽  
Post Induction ◽  
Myelocytic Leukemia ◽  
Group A ◽  
Group B ◽  
Disease Free

Abstract Acute myelocytic leukemia (AML) in Down Syndrome (DS) children is characterized by a young age of onset (< 2 years), a low white blood cell count and high frequency of Megakaryocytic leukemia. DS children with AML have higher disease free survival (DFS) rates as compared to non DS AML patients. Previous studies have suggested that intensification chemotherapy may not be necessary for the treatment of DS children with AML. The objective of this study was to clarify the effectiveness and toxicities of using high dose Cytosine Arabinoside (HD AraC) intensification in the treatment of DS AML. Clinical data for children (<14 years) with DS AML, diagnosed between September 2000 to May 2005, were retrieved from the hospital data base. Patients were divided into two groups; Group A patients received chemotherapy containing HD AraC, while Group B patients did not. A total of 15 patients were included, eight in Group A and seven in group B. The median age at diagnosis was 22 months (A=23 months, B=22 months). The two groups were matched regarding their clinical and laboratory parameters. There was no significant difference in DFS between groups A and B, 75% and 85% respectively (P = 0.82) at a mean observation period of 42.9 months for group A and 23.12 months for group B. The median time to relapse was 6 months for group A and 8 months for group B. The overall treatment related toxicity was higher in Group A patients but achieved only borderline significance (P = 0.06). However, when toxicity was assessed separately for induction and post induction phases of chemotherapy there were significantly more infectious events (17 v. 2; p=0.0006) in the post induction phase which includes HD AraC intensification in Group A. Even when only serious infections (bacteremia, fungal infection, sepsis) were included in the evaluation this difference persisted (7 v. 1; p=0.0339), with less toxicity for Group B patients. No such difference was noted between the two groups during induction chemotherapy. In conclusion the use of HD AraC in post-induction intensification phases for DS AML children does not improve DFS and is associated with more treatment related toxicity.

Concurrent Treatment with Denileukin Diftitox (DD) To Deplete T-Regulatory Cells Enhances Rebound Lymphocytosis and Eosinophilia in Patients Treated with High-Dose IL-2 (HDIL-2) for Metastatic Renal Cell Cancer (MRCC).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1729-1729
Author(s):  
Adi Gidron ◽  
John Eklund ◽  
Brenda Martone ◽  
Alfred W. Rademaker ◽  
Charles Goolsby ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
Statistical Significance ◽  
Cell Cancer ◽  
Peak Level ◽  
High Dose ◽  
Maximal Increase ◽  
Group A ◽  
Group B ◽  
Group D

Abstract Background: CD4+CD25+hi T cells (Treg) play a suppressive role in immune regulation. DD is an IL-2 receptor specific cytotoxin. We postulated depletion of Treg with DD may enhance immune effector cell populations after HDIL-2 treatment, including rebound lymphocytosis and also eosinophilia which has been reported to be involved in immune response to neoplasm (Mattes J Exp Med 197: 387, 2003). Methods: In this pilot study, 12 pts (8 male, median age 58 yrs) with MRCC were tx with HDIL-2 and DD in different schedules to determine safety and effect on immune response as manifested by changes in Treg, peak lymphocyte, and eosinophil counts. Pts were treated with IL-2 600,000 IU/kg Q8H on days (d) 1–5 and 15–19. Three (group A) and 4 (group B) pts were given 6 and 9ug/kg daily on d8–10 respectively, while 5 (group C) pts received 9ug/kg of DD on d −4 to −2. Nine (group D) pts with metastatic melanoma who received HDIL-2 as above but without DD were included as controls. Flow cytometry was done on days −4, 1,8,10,15,22 for group C and on days 1,8,10,15,22 for groups B, and D. CBC was obtained concurrent or within 24 hours of flow cytometry. Group A pts were evaluated for safety only and were excluded from analysis. Results: Prior to enrollment, all pts had undergone nephrectomy and four patients received interferon-alpha. One pt from group B withdrew from study and was not included in analysis. Administration of DD resulted in a median decline of 25% in Treg number (not significant). DD given before HDIL-2 was associated with a greater increase in Treg post HDIL-2. In Group C there was an increase of rebound median Treg count of 0.88k/ul compared with 0.060k/ul in group B (p=0.025). Absolute lymphocytosis was higher in the combined group getting DD compared to control (median maximal increase of 7.6 vs 4.7 k/ul, respectively) although the difference did not reach statistical significance. However, group C pts had a greater increase in absolute lymphocytosis than did group B pts in which absolute lymphocytosis actually decreased (median increase 10.6 vs. median decrease 0.4 k/ul, p=0.025). A higher peak level of eosinophilia was noted in groups B and C compared with group D (mean increase of 10.5 vs. 4.0 k/ul p=0.2). Group C had a greater peak eosinophilia than group B (11.2 vs 2.2 k/ul p=0.053) Toxicity was manageable and consistent with those seen with HDIL-2. Median HDIL-2 dose given was 21 (range, 14–28). No clinical responses were observed. Of 11 pts included in the analysis 1 pt from group A expired 68 weeks after enrollment. All remaining patients are alive. Survival from enrollment ranges from 11 to 93 weeks. Conclusion: Overall, the combination of DD and HDIL-2 results in a stimulatory effect as manifested by increased rebound lymphocytosis and eosinophilia compared to HDIL-2 alone. Administration of DD in conjunction with HDIL-2 was associated with a rebound in Treg that may be schedule and dose dependent. The results suggest an enhanced immune stimulatory effect as manifested by lymphocytosis and peak eosinophilia in group C. However, this stimulatory effect also extends to Treg that may prove detrimental clinically. Further exploration of these effects in immunotherapy naïve patients would be beneficial.

Thalidomide Based Regimens (TBR) for Relapsed/Refractory Multiple Myeloma Patients: Long Term Follow Up, Unmaintained Remissions and Disease Control after Subsequent Treatments.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4812-4812
Author(s):  
Maria Roussou ◽  
Efstathios Kastritis ◽  
Athanasios Anagnostopoulos ◽  
Evangelos Eleftherakis-Papaiakovou ◽  
Charis Matsouka ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Long Term Follow Up ◽  
Group A ◽  
Pulse Dexamethasone ◽  
Group B

Abstract Introduction: The effectiveness of thalidomide based regimens (TBR) in patients with relapsed/refractory multiple myeloma is well established. However, there are still limited data regarding the long term follow up after such regimens and the outcome of patients when they progress and they receive further treatment. In order to answer these questions we evaluated a series of 114 patients with relapsed/refractory multiple myeloma who were treated with TBR. None of these patients had previously received thalidomide, bortezomib or lenalidomide. Patients and Methods: All patients were treated with thalidomide and dexamethasone with or without other oral agents. More specifically 41 patients had received continuous thalidomide and pulse dexamethasone, 25 patients clarithromycin, continuous thalidomide and pulse dexamethasone, 43 patients intermittent thalidomide, pulse dexamethasone and cyclophosphamide and 5 patients continuous thalidomide, pulse dexamethasone and cyclophosphamide. Type of treatment at the time of progression after TBR, response to this treatment and progression free survival were recorded for each patient. Moreover, patients who received novel agents after progression to TBR, were divided into 2 subgroups, according to their resistance to thalidomide. In group A, patients had refractory or progressive myeloma while on TBR or within 2 months after discontinuation of TBR. In group B, myeloma progressed more than 2 months after discontinuation of TBR. Results: Among the 114 patients, 41 had not responded to TBR and 73 (64%) had achieved at least a partial response. The median PFS for all patients was 8 months. As of June 2007, 10 patients remain without progression from 28 to 81 months (median 54 months). Eight patients remain off treatment and without progression for a median of 56 months (range 28–81). Patients who did not respond to or progressed after TBR were analyzed for further treatment and outcome. Thirty eight patients (37%) died before receiving further treatment, 23 patients (23%) received conventional chemotherapy and 41 patients (40%) received continuous thalidomide and dexamethasone +/− clarithromycin or cyclophosphamide (17 patients), bortezomib and dexamethasone (7 patients), melphalan-bortezomib-dexamethasone and intermittent thalidomide (12 patients) or lenalidomide with dexamethasone (5 patients). Among these 41 patients, 24 were classified in group A (thalidomide resistant) and 17 in group B. Overall 17 (41%) achieved at least partial response after retreatment with novel agent-based regimens. A response was observed in 46% of patients in group A and in 35% of patients in group B. The median progression free survival of the 41 patients who received retreatment with novel agents was 9.2 months and the median survival was 17 months. Among the 23 patients who received conventional chemotherapy only five (21%) patients responded and the progression free survival and the median survival were 5.3 and 10.2 months, respectively. Conclusions: After an oral TBR regimen 6 (5%) patients remain without treatment and free of progression for more than 4 years. A significant number of patients who progressed after TBR and who received further treatment which included a novel agent achieved a response, including several patients who were resistant to TBR.

Stereotactic hypofractionated high-dose irradiation (STI) for stage I non-small cell lung cancer (NSCLC): Mature results in 300 cases of a Japanese multi-institutional study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7045-7045 ◽  
Author(s):  
H. Onishi ◽  
Y. Nagata ◽  
H. Shirato ◽  
K. Karasawa ◽  
K. Gomi ◽  
...  
Keyword(s):  
Total Dose ◽  
Local Control ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Pulmonary Complications ◽  
Stage I ◽  
High Dose ◽  
Stage Ib ◽  
Local Progression ◽  
Stage Ia

7045 Background: With the increasing accuracy of localization for tumor-bearing areas using various new techniques, hypofractionated or single high-dose stereotactic irradiation (STI) has been actively investigated for stage I NSCLC in Japan. The current study retrospectively evaluated Japanese multi-institutional results for high-dose STI for stage I NSCLC. Methods: From 1993 to 2003, stereotactic three-dimensional treatment was performed using 3–10 non-coplanar dynamic arcs or 6–20 static ports for a total of 300 stage I (median age, 75 years; T1N0M0, n = 193; T2N0M0, n = 107) patients with primary NSCLC (adenocarcinoma, n = 138; squamous cell carcinoma, n = 129; and others, n = 33) in 14 institutions. Totally 190 patients were medically inoperable, and other 110 were medically operable but selected STI. A total dose of 18–75 Gy at the isocenter was administered in 1–22 fractions. Median calculated biological effective dose (BED) was 108 Gy (range, 57–180 Gy). Results: Median follow-up period of survivors was 38 months (range; 2–128 months). Pulmonary complications of NCI-CTC criteria (version 2.0) grade ≥ 3 were noted in 9 patients (3.0%). Local progression occurred in 44 patients (14.7%), and 5-year local control rate was high (86%) for BED ≥100 Gy (n = 227) compared to 67% for <100 Gy (n = 73) (P < 0.001). Overall 5-year survival rates of operable and inoperable patients were 65% and 37%, respectively. Overall 5-year survival rates in operable cases was high (74%) for BED ≥100 Gy (n = 85) compared to 37% for <100 Gy (n = 24) (P < 0.01). In a subset of operable patients irradiated with BED ≥100, 3-year locally progression-free survival rates was high (81%) for stage IA (n = 60) compared to 67% for stage IB (n = 23) (P < 0.05) Conclusions: Local control and survival rates of STI for stage I NSCLC are better with BED ≥100 Gy compared to <100 Gy. Survival rates in selected patients (medically operable, BED ≥100 Gy) were excellent, and potentially comparable to those of surgery. Stage IB patients displayed higher rate of local progression than stage IA. We have started multi-institutional prospective study for stage IA NSCLC with a schedule of total dose of 48 Gy in 4 fractions during 4–8 days. No significant financial relationships to disclose.

Carboplatin-Paclitaxel Versus Cisplatin-Ifosfamide in the Treatment of Uterine Carcinosarcoma: A Retrospective Cohort Study

2014 ◽  
Vol 24 (7) ◽  
pp. 1256-1261 ◽  
Author(s):  
Domenica Lorusso ◽  
Fabio Martinelli ◽  
Maria Mancini ◽  
Italo Sarno ◽  
Antonino Ditto ◽  
...  
Keyword(s):  
Overall Survival ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Oncologic Outcomes ◽  
Uterine Carcinosarcoma ◽  
Suitable Alternative ◽  
Free Survival ◽  
Gynecology And Obstetrics ◽  
Group A ◽  
Group B

ObjectiveUterine carcinosarcoma (CS) is a rare neoplasm whose adjuvant treatment has not been yet defined. We report on the activity and toxicity of cisplatin-ifosfamide and carboplatin-paclitaxel as adjuvant treatments for patients with uterine CS.MethodsData of International Federation of Gynecology and Obstetrics (FIGO) stage I to IV uterine CS patients treated between 2006 and 2012 with adjuvant chemotherapy (cisplatin 20 mg/mq and ifosfamide 1500 mg/mq day 1 to 4 every 3 weeks plus prophylactic Granulocyte colony-stimulating factor (G-CSF) support [group A] or carboplatin area under the curve -5 (AUC-5) and paclitaxel 175 mg/mq d1q21 [group B]) were retrospectively reviewed. Progression-free survival, overall survival, and chemotherapy-related toxicities were compared between the 2 groups. A subanalysis of oncologic outcomes according to the sarcomatous component (homologous vs heterologous) was performed.ResultsForty-six women were evaluated—21 in group A and 25 in group B. At a median follow-up of 30 months, the median progression-free survival was 11.6 months (95% confidence interval [CI], 6.3–16.9) and 16.6 months (95% CI, 14.7–18.5) for group A and B, respectively (P= 0.20). The median overall survival was 17.1 months (95% CI, 12.6–21.5) and 35.1 months (95% CI, 26.3–43.7) for group A and B, respectively (P= 0.14). No differences were identified among heterologous or homologous components according to chemotherapy treatment. Toxicity profiles widely differ between treatment arms.ConclusionsBecause of the super imposable activity and the better toxicity profile, carboplatin-paclitaxel may be a suitable alternative to cisplatin-ifosfamide in the treatment of uterine CS.

scholarly journals Abiraterone versus bicalutamide in combination with gonadotropin releasing hormone antagonist therapy for high risk metastatic hormone sensitive prostate cancer.

2021 ◽  
Author(s):  
Takashi Ueda ◽  
Takumi Shiraishi ◽  
Saya Ueda ◽  
Motoharu Ohashi ◽  
Toru Matsugasumi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Progression Free Survival ◽  
Gonadotropin Releasing Hormone ◽  
Free Survival ◽  
Releasing Hormone ◽  
Group A ◽  
Psa Progression ◽  
Hormone Sensitive ◽  
Group B

Abstract ObjectivesTo compare the efficacy of abiraterone with that of bicalutamide in combination with gonadotropin-releasing hormone antagonist treatment for high risk metastatic hormone-sensitive prostate cancer patients.MethodsOne hundred and forty-nine patients with high risk metastatic hormone-sensitive prostate cancer at our hospital and affiliated hospitals between December 2013 and July 2020 were retrospectively identified. Fifty patients were administered abiraterone (1000mg/day) plus prednisolone (5mg/day) with gonadotropin-releasing hormone antagonist (degarelix) (group A) and 99 patients were administered bicalutamide (80mg/day) with gonadotropin-releasing hormone antagonist (group B). ResultsPSA- progression-free survival of group A was significantly longer than that of group B. Abiraterone therapy and Gleason score were significant independent factors for PSA-progression-free survival. By propensity score matching, total 56 matched patients were obtained. PSA-PFS (p<0.001) and OS (p=0.0071) of high risk mHNPC patients were significantly longer in abiraterone group of matched patients. Abiraterone therapy and Gleason score were still shown to be significant independent factors for PSA-PFS in matched patients.ConclusionsPSA-progression-free survival and overall survival in patients who were treated with abiraterone in combination with gonadotropin releasing hormone antagonist were significantly better than those of bicalutamide.

scholarly journals A Long Survival of III-IVb Stage Nasopharyngeal Carcinoma Treated with IMRT with or without Nimotuzumab: a Propensity Score-matched Analysis

2019 ◽  
Author(s):  
Wang Zhi-Qiang ◽  
Mei Qi ◽  
Li Ji-Bin ◽  
You Rui ◽  
Liu You-Ping ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Propensity Score ◽  
Intensity Modulated Radiotherapy ◽  
Progression Free Survival ◽  
Chinese Patients ◽  
Term Survival ◽  
Free Survival ◽  
Distant Failure ◽  
Group A ◽  
Group B

Abstract Backgrounds: To assess the efficacy of Nimotuzumab in combination with first-line treatment of chemoradiotherapy of Chinese patients with primary III-IVb stage nasopharyngeal carcinoma. Methods: Patients with primary locoregionally advanced nasopharyngeal carcinoma who were treated with intensity-modulated radiotherapy (IMRT) and concurrent Cisplatin-based chemotherapy between January, 2008 and December, 2013 at a single institution were retrospectively reviewed. Group A received at least 6 doses of Nimotuzumab; Group B did not received Nimotuzumab. A propensity score matching method was used to match patients from each group in a 1:3 ratio. Results: In total, 730 eligible patients were propensity-matched, with 184 patients in Group A and 546 in Group B. There were no significant differences in patient and tumor characteristics between Group A and Group B. At a median follow-up of 74.78 months (range 3.53–117.83 months), locoregional recurrence, distant failure and death were observed in 10.68%, 11.10% and 16.03% of all patients, respectively. Estimated 5-year locoregional relapse–free survival, distant metastasis–free survival, progression-free survival and overall survival in the Group A versus Group B were: 85.34% versus 89.79% (P=0.156), 93.09% versus 85.61% (P = 0.012), 79.96% versus 77.99% (P = 0.117) and 88.91% versus 78.30% (P=0.006), respectively. Conclusions: This nimotuzumab-containing regimen resulted in a better long-term survival in III-IVb stage NPC patients, and warrants further prospective evaluation.

scholarly journals EFEK PEMBERIAN ANABOLIK ANDROGENIK STEROID INJEKSI DOSIS RENDAH DAN TINGGI TERHADAP GAMBARAN HISTOPATOLOGI HATI DAN OTOT RANGKA TIKUS WISTAR (Rattus Novergicus)

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Pamela K. Sari ◽  
Poppy M. Lintong ◽  
Lily L. Loho
Keyword(s):  
Protein Synthesis ◽  
Wistar Rats ◽  
Low Dose ◽  
Anabolic Steroids ◽  
Inflammatory Cells ◽  
High Dose ◽  
Group A ◽  
Androgenic Anabolic Steroids ◽  
Group B ◽  
Group D

Abstract: Androgenic-anabolic steroids (AAS) are synthetic derivatives of the male hormone endogenous testosterone that stimulates anabolic (protein synthesis) and androgenic effects (masculinization). Long-term usage of AAS can result in liver damage. However, physiological concentrations of testosterone can stimulate protein synthesis which lead to an increase in muscle size, body mass, and endurance. This study aimed to determine the histopathology of liver and skeletal muscles of wistar rats that were given low dose and high dose injection of AAS. Subjects were 21 wistar rats divided into 7 groups. Group A was given standard pellets for 56 days (negative control), terminated on days 29,43, and 57. Group B was treated with low-dose AAS injection and standard pellets for 28 days, terminated on day 29. Group C was treated with low-dose AAS injection and standard pellets for 42 days, terminated on day 43. Group D was treated with low-dose AAS injection and standard pellets for 56 days, terminated on day 57. Group E was treated with high-dose AAS injection and standard pellets for 28 days, terminated on day 29. Group F was treated with high-dose AAS injection and standard pellets for 42 days, terminated on day 43. Group G was treated with high-dose AAS injection and standard pellets for 56 days, terminated on day 57. The results showed that the histopathology of liver and muscles in group A was still normal. In group B, the architecture of liver was still normal with a few inflammatory cells around the Kiernan triangle while in muscle the ratio of myofibril diameter was 1.28:1. In group C and group D, there were widening of the hepatic artery, bile duct, and portal vein containing blood fibrin, and inflammatory cells around the Kiernan triangle. The ratio of myofibril diameter was 1.43:1 in group C and 2.14:1 in group D. In group E, F and G, there were micro-vesicular fatty cells in the peripheral part of the liver meanwhile the myofibril diameter ratio of the muscles in group E was 1.43:1, group F 2.1:1, and group G 2.28:1. Conclusion: Administration of AAS injection of low dose and high dose for less than 4 weeks could result in inflammation, dilation of the portal vein, hepatic artery and bile duct meanwhile administration of AAS for over 4 weeks could ressult in focal fatty liver (steatosis). The administration of AAS injection of low dose and high dose for 4,6 and 8 weeks reslutid in enlargement of skeletal muscle (muscle hypertrophy).Keywords: androgenic-anabolic steroids, liver, skeletal muscleAbstrak: Anabolik Androgenik Steroid (AAS) adalah derivat sintetis dari hormon sex testosteron endogen pria, yang merangsang efek anabolik (sintesis protein) dan androgenik (maskulinisasi). Penggunaan AAS jangka panjang dapat mengakibatkan terjadinya kerusakan hati namun secara fisiologi testosteron dapat menstimulasi sintesis protein sehinggaberdampak pada peningkatan ukuran otot, massa tubuh dan ketahanan tubuh. Penelitian ini bertujuan untuk mengetahui gambaran histopatologi hati dan otot rangka wistar yang diberikan AAS injeksi dosis rendah dan dosis tinggi. Subjek penelitian 21 ekor wistar yang dibagi menjadi 7 kelompok. Kelompok A diberi pelet standar selama 56 hari (kontrol negatif), terminasi pada hari ke-29, 43, dan 57. Kelompok B diberi perlakuan AAS injeksi dosis rendah dan pelet standar selama 28 hari, terminasi hari ke-29. Kelompok C diberi AAS injeksi dosis rendah dan pelet standar selama 42 hari, terminasi hari ke-43. Kelompok D diberi AAS injeksi dosis rendah dan pelet standar selama 56 hari, terminasi hari ke-57. Kelompok E diberi perlakuan AAS injeksi dosis tinggi dan diberi pelet standar selama 28 hari, terminasi hari ke-29. Kelompok F diberi perlakuan AAS injeksi dosis tinggi dan diberi pelet standar selama 42 hari, terminasi hari ke-43. Kelompok G diberi perlakuan AAS injeksi dosis tinggi dan diberi pelet standar selama 56 hari, terminasi hari ke-57. Hasil penelitian menunjukkan pada kelompok A didapatkan gambaran histopatologi hati normal sedangkan pada otot tidak terdapat perubahan. Pada kelompok B didapatkan arsitektur hati masih normal dengan sedikit sel radang disekitar segitiga Kiernan sedangkan pada otot terlihat diameter miofibril ratio 1,28:1. Pada kelompok C dan D terlihat pelebaran arteri hepatika, duktus biliaris, dan vena porta yang berisi fibrin darah, serta sel-sel radang di sekitar segitiga Kiernan. Pada kelompok C diameter miofibril ratio 1,43;1 dan pada kelompok D 2,14:1. Pada kelompok E, F dan G terdapat sel-sel perlemakan mikrovesikuler di perifer sedangkan pada otot diameter miofibril ratio kelompok E 1,43:1, kelompok F 2,1:1, dan kelompok G 2,28:1. Simpulan: Pada pemberian AAS injeksi dosis rendah dan dosis tinggi kurang dari 4 minggu terjadi peradangan hati, pelebaran vena porta, arteri hepatika dan duktus biliaris sedangkan lebih dari 4 minggu terdapat perlemakan (steatosis) fokal hati. Pemberian AAS injeksi dosis rendah dan tinggi dalam waktu 4,6 dan 8 minggu menunjukkan pembesaran otot rangka (hipertrofi otot).Kata kunci: AAS, hati, otot rangka

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