Treatment of ocular melanoma metastatic to the liver by hepatic arterial chemotherapy.

PURPOSE Ocular melanoma is characterized by a high rate of liver metastases and is associated with a median survival time less than 5 months. There is no standard treatment available. Treatment strategies have, without success, relied on the experience with metastatic cutaneous melanoma. The only effective treatment is chemoembolization using cisplatin and polyvinyl sponge, which has never become accepted on a large scale. The objective of the study was to establish prospectively the efficacy and toxicity of hepatic intraarterial fotemustine, a third-generation nitrosourea, in patients with liver metastases from ocular melanoma. PATIENTS AND METHODS Thirty-one patients were subjected to laparotomy to place a totally implantable catheter into the hepatic artery and received fotemustine 100 mg/m2 as a 4-hour infusion, first once a week for four times and then, after a 5-week rest period, every 3 weeks until progression or toxicity. Cox regression models were used to assess the prognostic role of patient survival characteristics. RESULTS Objective responses were observed in 12 of 30 assessable patients (40%; 95% confidence interval, 22% to 59%). The median duration of response was 11 months and the median overall survival time, 14 months. Lactate dehydrogenase (LDH) appeared to be the strongest prognostic factor for survival. Toxicity was minimal and treatment could be administered on an outpatient basis. CONCLUSION The results of hepatic arterial chemotherapy with fotemustine produced a high response rate and survival similar to chemoembolization therapy. It involves no major toxicity and preserves the quality of life. To assess further its effectiveness, a randomized study to compare hepatic intraarterial versus intravenous chemotherapy is being planned.

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Subcutaneous Alemtuzumab (Campath) in Fludarabine-Refractory CLL: Final Results of the CLL2H Trial of the GCLLSG and Comprehensive Analysis of Prognostic Markers

Blood ◽

10.1182/blood.v112.11.329.329 ◽

2008 ◽

Vol 112 (11) ◽

pp. 329-329 ◽

Cited By ~ 3

Author(s):

Stephan Stilgenbauer ◽

Thorsten Zenz ◽

Dirk Winkler ◽

Andreas Bühler ◽

Silja Groner ◽

...

Keyword(s):

Survival Time ◽

Tp53 Mutation ◽

Cox Regression ◽

Detection Threshold ◽

Injection Site Reaction ◽

Progression Free Survival ◽

Significant Prognostic Factor ◽

Outpatient Basis ◽

Insufficient Response ◽

Grade 3

Abstract The multicenter CLL2H trial of the GCLLSG evaluated subcutaneous alemtuzumab 3 × 30 mg weekly in fludarabine refractory CLL. From September 2002 to February 2006, 103 patients were enrolled and received at least one dose of alemtuzumab. Median age was 63 (35.1–81.8) years, 72% were male, 74% were Binet C, and a median of 3 (1–10) prior lines had been given. Unfavorable genetics were frequent (17p deletion: 29%, 11q deletion: 19%, unmutated IgVH: 68%, TP53 mutation 34%). Subcutaneous treatment was performed on an outpatient basis in 96% and had to be temporarily interrupted in 65 patients due to neutropenia (27%), anemia (3%), thrombocytopenia (8%), infections (36%), and was stopped early in 65 cases due to insufficient response (43%), hematotoxicity (14%) and infections (29%). The median alemtuzumab dose given was 722 (3–2203) mg. Toxicity during treatment period was mostly grade I/II apart from hematotoxicity. Grade 3/4 neutropenia, thrombocytopenia, anemia occurred in 56%, 57%, and 50% of patients, respectively. Grade 3/4 non-cytomegalovirus infection occurred in 29%. CMV reactivation was observed in 15 % total, Grade 3/4 occurred in 8% of patients. All CMV episodes were successfully treated with anti-CMV therapy, and there was no CMV-related death. Injection site reaction occurred in 34% and was grade 1 or 2 except in 1 patient who had grade 3 reaction. Pegfilgrastim prophylaxis was scheduled for the second half of the trial. Grade 3/4 neutropenia occurred in 70% vs 46% and non-CMV infections occurred in 32% vs 24% in the first and second half, respectively. Development of anti-alemtuzumab antibody was assessed in samples from 21 patients. Plasma anti-alemtuzumab antibody was detectable in only 1 patient, who had a concentration marginally above the detection threshold and was found to be negative in a re-test 5 months later. Stable disease was achieved in this patient. After a median follow-up time of 37.9 months, there were 75 (73%) deaths, 56% due to disease progression, 31% due to infection, and 13% not related to CLL. Overall response rate was 34% (CR 4%, PR 30%), median progression free survival time was 7.7 months, and median overall survival time was 19.1 months. Clinical and biologic parameters (age, sex, B-symptoms, stage, ECOG, number of prior lines, node size, hepato-spenomegaly, WBC, LDH, β2-MG, TK, VH status, genomic aberrations and TP53 mutation) were evaluated for their prognostic role. In univariate analyses, OS was significantly inferior for age > 65 y (12.2 vs 29.0 mo, p<.001), ECOG > 1 (10.8 vs 21.5 mo, p=.011), TK > median (26U/L) (14.9 vs 29.0 mo, p=.001), and β2- MG > 5 (13.6 vs 27.2 mo, p=.004). Median PFS and OS were not different for 17p-, 11q-, other cytogenetic and TP53 mutation subgroups. Multivariate analysis by Cox regression revealed only age (HR 1.6, p<.001) as significant prognostic factor, while TK (p=.11), β2- MG (p=.089), and 17p- (p=.528) showed no significant impact. The choice of next therapy significantly affected survival. Seventy-four patients received subsequent salvage treatment or allogeneic stem cell transplantation (SCT). The median OS since next therapy in these patients was 11.5 months. The 2-year OS rate for allogeneic SCT as compared to other subsequent treatments (chemo-, immuno-, or chemoimmunotherapies) was 86% and 27% (p=0.009).

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Phase II clinical study of combination therapy with irinotecan and S-1(IRIS) for inoperable recurrent advanced colorectal cancer (2nd report): For Hokkaido Gastrointestinal Cancer Study Group (HGCSG)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4105 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4105-4105

Author(s):

Y. Komatsu ◽

S. Yuki ◽

I. Iwanaga ◽

M. Kudo ◽

M. Tateyama ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Study ◽

Combination Therapy ◽

Survival Time ◽

Phase Ii ◽

Advanced Colorectal Cancer ◽

High Response Rate ◽

Phase Iii ◽

Outpatient Basis ◽

Phase Ii Clinical Study

4105 Background: We planned to conduct a phase II clinical study of combination therapy with irinotecan and S-1, a new oral anticancer drug of the fluorinated pyrimidine type. We reported the interim reports of this study in colorectal cancer patients at ASCO 2006. Methods: The antitumor effect was the primary endpoint, while the safety, progression-free survival time, and median survival time were the secondary endpoints. The subjects were untreated patients with inoperable advanced colorectal cancer aged 20–75 years. Irinotecan was administered at a dose of 100 mg/m2 (on days 1 and 15) as an intravenous infusion over 90 minutes, and oral S-1 (40 mg/m2) was administered after breakfast and dinner and then withdrawn for 2 weeks. Results: Forty patients were enrolled in the present study. There were 23 men and 17 women. The median age was 62 years (range: 34 to 74 years). Two patients showed grade 4 neutropenia, but the next course could be given safely after dose reduction. Three patients had grade 3 diarrhea, but therapy could be continued with addition of an antidiarrhea drug. No other serious adverse reactions occurred (either hematological or non-hematological), and all patients could receive therapy safely on an outpatient basis. Forty pts. are evaluable for efficacy: RR was 52.5% (CR 1, PR 20, SD 17, PD 2, 95% CI, 37–68%) and Disease Control Rate (CR+PR+SD) was seen in 96.0% of pts. PFS of this regimen is 311 days. MST is not reached. Conclusions: IRIS therapy achieved a high response rate and could be given safely. These findings suggest that the therapy has potential as first-line treatment for inoperable advanced recurrent colorectal cancer. It seems that IRIS is a good treatment equal to FOLFIRI. Non-inferiority randomized phase III trial of IRIS vs. mFOLFOX6 (IFOX study) was planned, and it has been already started now. The latest data will be reported at the meeting. No significant financial relationships to disclose.

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High rate lond term response after one year interferon (IFN) plus ribavirine treatment for hepatitis C relapsers. Results of a controlled randomized study in 191 patients

Journal of Hepatology ◽

10.1016/s0168-8278(01)80613-9 ◽

2001 ◽

Vol 34 (0) ◽

pp. 167

Author(s):

E Boucher

Keyword(s):

Hepatitis C ◽

Randomized Study ◽

High Rate ◽

One Year ◽

Term Response

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Survival after surgery among patients with cholangiocarcinoma in Northeast Thailand according to anatomical and morphological classification

BMC Cancer ◽

10.1186/s12885-021-08247-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chaiwat Tawarungruang ◽

Narong Khuntikeo ◽

Nittaya Chamadol ◽

Vallop Laopaiboon ◽

Jaruwan Thuanman ◽

...

Keyword(s):

Survival Rate ◽

Survival Time ◽

Median Survival ◽

Median Survival Time ◽

Cox Regression ◽

Survival Rates ◽

Care Program ◽

Tumor Location ◽

Northeast Thailand ◽

Curative Surgery

Abstract Background Cholangiocarcinoma (CCA) has been categorized based on tumor location as intrahepatic (ICCA), perihilar (PCCA) or distal (DCCA), and based on the morphology of the tumor of the bile duct as mass forming (MF), periductal infiltrating (PI) or intraductal (ID). To date, there is limited evidence available regarding the survival of CCA among these different anatomical and morphological classifications. This study aimed to evaluate the survival rate and median survival time after curative surgery among CCA patients according to their anatomical and morphological classifications, and to determine the association between these classifications and survival. Methods This study included CCA patients who underwent curative surgery from the Cholangiocarcinoma Screening and Care Program (CASCAP), Northeast Thailand. The anatomical and morphological classifications were based on pathological findings after surgery. Survival rates of CCA and median survival time since the date of CCA surgery and 95% confidence intervals (CI) were calculated. Multiple cox regression was performed to evaluate factors associated with survival which were quantified by hazard ratios (HR) and their 95% CIs. Results Of the 746 CCA patients, 514 had died at the completion of the study which constituted 15,643.6 person-months of data recordings. The incidence rate was 3.3 per 100 patients per month (95% CI: 3.0–3.6), with median survival time of 17.8 months (95% CI: 15.4–20.2), and 5-year survival rate of 24.6% (95% CI: 20.7–28.6). The longest median survival time was 21.8 months (95% CI: 16.3–27.3) while the highest 5-year survival rate of 34.8% (95% CI: 23.8–46.0) occurred in the DCCA group. A combination of anatomical and morphological classifications, PCCA+ID, was associated with the longest median survival time of 40.5 months (95% CI: 17.9–63.0) and the highest 5-year survival rate of 42.6% (95% CI: 25.4–58.9). The ICCA+MF combination was associated with survival (adjusted HR: 1.45; 95% CI: 1.01–2.09; P = 0.013) compared to ICCA+ID patients. Conclusions Among patients receiving surgical treatment, those with PCCA+ID had the highest 5-year survival rate, which was higher than in groups classified by only anatomical characteristics. Additionally, the patients with ICCA+MF tended to have unfavorable surgical outcomes. Showed the highest survival association. Therefore, further investigations into CCA imaging should focus on patients with a combination of anatomical and morphological classifications.

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High-Rate Transition Metal-based Cathode Materials for Battery-Supercapacitor Hybrid Devices

Nanoscale Advances ◽

10.1039/d1na00523e ◽

2021 ◽

Author(s):

Cong Wang ◽

Zehao Song ◽

Pei Shi ◽

Lin Lv ◽

Houzhao Wan ◽

...

Keyword(s):

Large Scale ◽

Rapid Development ◽

Electronic Devices ◽

High Rate ◽

Specific Power ◽

Energy Storage Devices ◽

Storage Devices ◽

Electrochemical Devices ◽

Hybrid Devices ◽

Scale Grid

With the rapid development of portable electronic devices, electric vehicles and large-scale grid energy storage devices, it needs to reinforce specific energy and specific power of related electrochemical devices meeting...

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High rate of second ACL injury following ACL reconstruction in male professional footballers: an updated longitudinal analysis from 118 players in the UEFA Elite Club Injury Study

British Journal of Sports Medicine ◽

10.1136/bjsports-2020-103555 ◽

2021 ◽

pp. bjsports-2020-103555

Author(s):

Francesco Della Villa ◽

Martin Hägglund ◽

Stefano Della Villa ◽

Jan Ekstrand ◽

Markus Waldén

Keyword(s):

Acl Reconstruction ◽

Cox Regression ◽

Injury Rate ◽

Acl Injury ◽

High Rate ◽

Football Players ◽

Professional Football ◽

Cox Regression Analysis ◽

Career Length ◽

Increased Risk

BackgroundStudies on subsequent anterior cruciate ligament (ACL) ruptures and career length in male professional football players after ACL reconstruction (ACLR) are scarce.AimTo investigate the second ACL injury rate, potential predictors of second ACL injury and the career length after ACLR.Study designProspective cohort study.SettingMen’s professional football.Methods118 players with index ACL injury were tracked longitudinally for subsequent ACL injury and career length over 16.9 years. Multivariable Cox regression analysis with HR was carried out to study potential predictors for subsequent ACL injury.ResultsMedian follow-up was 4.3 (IQR 4.6) years after ACLR. The second ACL injury rate after return to training (RTT) was 17.8% (n=21), with 9.3% (n=11) to the ipsilateral and 8.5% (n=10) to the contralateral knee. Significant predictors for second ACL injury were a non-contact index ACL injury (HR 7.16, 95% CI 1.63 to 31.22) and an isolated index ACL injury (HR 2.73, 95% CI 1.06 to 7.07). In total, 11 of 26 players (42%) with a non-contact isolated index ACL injury suffered a second ACL injury. RTT time was not an independent predictor of second ACL injury, even though there was a tendency for a risk reduction with longer time to RTT. Median career length after ACLR was 4.1 (IQR 4.0) years and 60% of players were still playing at preinjury level 5 years after ACLR.ConclusionsAlmost one out of five top-level professional male football players sustained a second ACL injury following ACLR and return to football, with a considerably increased risk for players with a non-contact or isolated index injury.

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Rapid evolution at the Drosophila telomere: transposable element dynamics at an intrinsically unstable locus

Genetics ◽

10.1093/genetics/iyaa027 ◽

2020 ◽

Vol 217 (2) ◽

Author(s):

Michael P McGurk ◽

Anne-Marie Dion-Côté ◽

Daniel A Barbash

Keyword(s):

Copy Number ◽

Large Scale ◽

Insertion Site ◽

Rapid Evolution ◽

Interspecific Variation ◽

High Rate ◽

Evolutionary Strategy ◽

Control Mechanisms ◽

Genetic Conflict ◽

Number Variation

AbstractDrosophila telomeres have been maintained by three families of active transposable elements (TEs), HeT-A, TAHRE, and TART, collectively referred to as HTTs, for tens of millions of years, which contrasts with an unusually high degree of HTT interspecific variation. While the impacts of conflict and domestication are often invoked to explain HTT variation, the telomeres are unstable structures such that neutral mutational processes and evolutionary tradeoffs may also drive HTT evolution. We leveraged population genomic data to analyze nearly 10,000 HTT insertions in 85 Drosophila melanogaster genomes and compared their variation to other more typical TE families. We observe that occasional large-scale copy number expansions of both HTTs and other TE families occur, highlighting that the HTTs are, like their feral cousins, typically repressed but primed to take over given the opportunity. However, large expansions of HTTs are not caused by the runaway activity of any particular HTT subfamilies or even associated with telomere-specific TE activity, as might be expected if HTTs are in strong genetic conflict with their hosts. Rather than conflict, we instead suggest that distinctive aspects of HTT copy number variation and sequence diversity largely reflect telomere instability, with HTT insertions being lost at much higher rates than other TEs elsewhere in the genome. We extend previous observations that telomere deletions occur at a high rate, and surprisingly discover that more than one-third do not appear to have been healed with an HTT insertion. We also report that some HTT families may be preferentially activated by the erosion of whole telomeres, implying the existence of HTT-specific host control mechanisms. We further suggest that the persistent telomere localization of HTTs may reflect a highly successful evolutionary strategy that trades away a stable insertion site in order to have reduced impact on the host genome. We propose that HTT evolution is driven by multiple processes, with niche specialization and telomere instability being previously underappreciated and likely predominant.

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