scholarly journals Patterns of metastasis in follicular thyroid carcinoma and the difference between early and delayed presentation

2017 ◽  
Vol 99 (2) ◽  
pp. 151-154 ◽  
Author(s):  
R Parameswaran ◽  
J Shulin Hu ◽  
N Min En ◽  
WB Tan ◽  
NK Yuan
Keyword(s):  
Metastatic Disease ◽  
Thyroid Surgery ◽  
Survival Data ◽  
External Beam Radiotherapy ◽  
Good Prognosis ◽  
Delayed Presentation ◽  
Common Site ◽  
Significant Difference ◽  
The Difference

Introduction Follicular thyroid cancer (FTC) has a good prognosis if treated early. The aim of this study was to look at the difference in outcomes in those who presented with metastasis early or late in their disease. Methods A retrospective cohort study was conducted of patients diagnosed with FTC (n=91) treated between 2000 and 2013. Demographic, laboratory, pathological and survival data were collected and analysed. Results Metastatic FTC was diagnosed in 20 cases (22%). The median age at diagnosis was 65 years (range: 17–86 years) and 65% of the patients were female. Twelve patients (60%) were diagnosed with metastatic disease at presentation, with the bones being the most common site (75%). In the remaining eight cases (40%), metastasis developed at a median of 4.5 years (range: 2–8 years) after initial thyroid surgery, lungs being the most common site (50%). Eighteen patients (90%) underwent surgical intervention for the primary disease. Sixteen patients (80%) received adjuvant radioactive iodine and eight (40%) received external beam radiotherapy. Widely invasive follicular cancer was the predominant histological diagnosis (90%). No prognostic association was observed with any of the parameters studied. The overall disease specific mortality rate was 40%. There was no significant difference in mortality between those who presented with metastatic disease and those who developed metastasis during the follow-up period (33% vs 50%, p=0.61). Conclusions The clinical outcome and prognosis for cases with metastatic disease is generally poor. Despite this, almost half of the patients in our study were still alive at a median follow-up of 5.5 years, regardless of whether they were diagnosed with metastatic disease on initial presentation or whether they developed metastasis after initial thyroid surgery.

scholarly journals Decreased Survival and Increased Rate of Fibrotic Progression in Essential Thrombocythemia Chronicled after the FDA Approval Date of Anagrelide

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4287-4287
Author(s):  
Ayalew Tefferi ◽  
Natasha Szuber ◽  
Kebede H. Begna ◽  
Mrinal M. Patnaik ◽  
Michelle A. Elliott ◽  
...  
Keyword(s):  
Essential Thrombocythemia ◽  
Survival Data ◽  
Mayo Clinic ◽  
World Health ◽  
Bleeding Complications ◽  
Fda Approval ◽  
Significant Difference ◽  
Risk Distribution ◽  
The Difference

Abstract Background: Anagrelide clinical trials in myeloproliferative neoplasms (MPN) were pioneered by the late Murray N. Silverstein M.D.(1928-1998) of the Mayo Clinic and the first publication involving 20 patients, including 17 with essential thrombocythemia (ET), appeared in 1988 (study launched in October 1985) (N Engl J Med 1988;318:1292). A larger study involving 577 patients, including 335 with ET, was subsequently published in 1992 and led to FDA approval in March 1997 (Am J Med 1992;92:69). Anagrelide has also been evaluated, in controlled studies, for its efficacy and safety as first-line therapy for ET; the results of these studies suggested that anagrelide was not inferior to hydroxyurea, in one study (Blood 2013;121:1720), but might have been harmful to patients in, the second study (N Engl J Med 2005;353:33); in the latter study, patients receiving anagrelide experienced higher incidences of arterial thrombosis, bleeding complications and fibrotic progression. These observations raised significant concern regarding an adverse survival impact of anagrelide in ET; unfortunately, the follow-up period of formal controlled studies were too short to accurately address the particular concern. Methods: The current study represents a retrospective examination of the potential impact of anagrelide therapy on survival and disease complication rates in ET. The study population was recruited from a consecutive cohort of adult patients (age ≥18 years) with MPN seen at the Mayo Clinic from 10/27/1967 through 12/29/2017. Diagnosis and determinations of fibrotic and/or leukemic transformations, were in strict accordance with the 2016 World Health Organization criteria (Blood 2016;127:2391). Statistical analyses were based on clinical and laboratory parameters obtained at the time of first referral to the Mayo Clinic which, in the majority of cases, coincided with initial diagnosis. All patients were followed from diagnosis until death or date of last follow-up or contact. Follow-up was until April 2018 and data collected via medical records or in certain cases, by directly contacting patients or their physicians. Survival and time-to-event curves were prepared using the Kaplan-Meier method and compared by the log-rank test. The JMP® Pro 13.0.0 software package was used for all analyses (SAS Institute, Cary, NC, USA). Results: 1,076 patients with ET were considered (median age 58 years; females 63%); international prognostic scoring system for ET (IPSET; Blood 2012;120:1197) risk distribution was 28% high, 42% intermediate and 30% low; driver mutational status was JAK2 61%, CALR 25%, triple-negative 11% and MPL 3%. Comparison of cases diagnosed before (n=433) and after (n=643) the FDA approval date of anagrelide (1997) revealed the former cohort to be younger (median 57 vs 60 years; p=0.003), although the difference in IPSET risk distribution was not significant (p=0.14). Figures 1a, 1b, 1c and 1d illustrate overall (OS), myelofibrosis-free (MFFS), leukemia-free (LFS) and thrombosis-free survival data comparing ET patients diagnosed before and after the 1997 FDA approval date for anagrelide; a significant difference was apparent for OS (p=0.006; HR 1.4, 95% CI 1.1-1.7) and MFFS (p<0.001; HR 4.2, 95% CI 2.7-6.5), in favor of patients diagnosed prior to 1997; during multivariable analysis that included IPSET and sex, the significant difference in both OS and MFFS were sustained; the difference in OS was most apparent after the first decade of diagnosis with 10- and 20-year survival rates of 75% and 50% for diagnosis prior to 1997 vs 72% and 21% for diagnosis between 1997 and 2017 (figure 1a); the 10- and 20-year risk of fibrotic progression was 3% and 15% for diagnosis prior to 1997 and 14% and 46% for diagnosis after 1997 (figure 1b); there was no impact on LFS (p=0.32; Figure 1c) or TFS (p=0.18; Figure 1d). Similarly stratified survival data in polycythemia vera (n=665) and primary myelofibrosis (n=1,282) showed no impact on survival (p=0.3 and 0.17, respectively). Conclusions: In a retrospective, but otherwise unbiased comparative analysis, we show significantly decreased OS and MFFS in ET patients diagnosed after the FDA approval date of anagrelide (1997); the increased risk of fibrotic progression noted is consistent with results of earlier prospective data (N Engl J Med 2005;353:33). Our observations regarding OS requires confirmation in a prospective controlled setting. Disclosures No relevant conflicts of interest to declare.

scholarly journals POS0208 GENDER DIFFERENCES IN RESPONSE TO BIOLOGICALS. WOMEN FARE WORSE ACROSS INFLAMMATORY ARTHRITIS DISEASES - DATA FROM THE BIOREG

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 320.1-321
Author(s):  
E. Loibner ◽  
V. Ritschl ◽  
B. Leeb ◽  
P. Spellitz ◽  
G. Eichbauer-Sturm ◽  
...  
Keyword(s):  
Gender Differences ◽  
Psoriatic Arthritis ◽  
Gender Difference ◽  
Disease Activity ◽  
Inflammatory Arthritis ◽  
Tnf Inhibitors ◽  
Significant Difference ◽  
The Difference ◽  
All Diseases

Background:Gender differences in prevalence and disease course are known in various rheumatic diseases; however, investigations of gender difference concerning therapeutical response have yielded variable results.Objectives:The aim of this retrospective study was to investigate, whether a gender difference in response rate to biological disease-modifying antirheumatic drugs (bDMARDs) and apremilast in bDMARD-naïve patients could be observed across the three most prevalent inflammatory arthritis diseases: rheumatoid arthritis (RA), spondylarthritis (SpA) and psoriatic arthritis (PsA). Additionally, a response to individual TNF blockers was investigated in this respect.Methods:Data from bDMARD-naïve RA-, SpA- and PsA-patients from Bioreg, the Austrian registry for biological DMARDs in rheumatic diseases, were used. Patients with a baseline (Visit 1=V1) and follow-up visits at 6 months (Visit 2=V2) and 12 months (Visit 3=V3) were included and response to therapy with TNF-inhibitors (TNFi), furthermore to therapy with rituximab, tocilizumab and apremilast was analyzed according to gender. The remaining bDMARDs were not analyzed due to small numbers. Key response-parameter for RA was disease activity score (DAS28), whereas for PsoA the Stockerau Activity Score for Psoriatic Arthritis (SASPA) and for SpA the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were employed; in addition, the Health assessment Questionnaire (HAQ) was used. Data were analyzed in R Statistic stratified by gender using Kruskal-Wallis and Wilcoxon tests.Results:354 women and 123 men with RA (n=477), 81 women and 69 men with PsA (n=150), 121 women and 191 men with SpA (n=312) were included. No significant differences in biometrics was seen between female and male patients at baseline in all diseases.In RA patients overall DAS28 decreased from baseline (V1) to V2 and V3 (DAS28: V1: male: 4.38 [3.66, 5.11], female: 4.30 [3.68, 5.03], p(m/f) = 0.905; V2: male: 2.66 [1.73, 3.63], female: 3.10 [2.17, 3.98], p(m/f) = 0.015; V3: male: 2.25 [1.39, 3.36], female: 3.01 [1.87, 3.87], p(m/f) = 0.002). For TNF inhibitors (n=311), there was a significant difference between genders at V2 (Fig.1a). Patients receiving Rituximab (n=41) displayed a significantly higher DAS28 at baseline in females, which diminished in the follow up: V1: (p(m/f) p=0.002; V2: p=0.019; V3: p=0.13); response to tocilizumab (n=63) did not show any gender differences.In PsA patients overall SASPA decreased from baseline (V1) to V2 and V3 (SASPA: V1: male: 4.00 [2.80, 5.20], female: 4.40 [2.80, 5.80], p(m/f) = 0.399; V2: male: 2.20 [1.20, 3.50], female: 3.40 [2.00, 5.00], p(m/f) = 0.071; V3: male: 1.80 [0.80, 2.70], female: 3.01 [2.35, 4.80], p(m/f) = 0.001). For TNF inhibitors (n=79), there was a significant difference between genders at V3 (Fig 1a). For Apremilast (n=39), there was a significant difference between genders at V2 (Fig.1c).In SpA patients overall BASDAI decreased from baseline (V1) to V2 and V3 (BASDAI: V1: male: 4.70 [2.88, 6.18], female: 4.80 [3.30, 6.20], p(m/f) = 0.463; V2: male: 3.05 [2.00, 4.60], female: 3.64 [2.62, 5.41], p(m/f) = 0.039; V3: male: 3.02 [1.67, 4.20], female: 3.65 [2.18, 5.47], p(m/f) = 0.016). In V3 a differential BASDAI in response to TNFi (n=299) was observed (Fig.1a).Possible differences of response to individual TNFi (etanercept, infliximab, other TNFi) measured by HAQ were investigated in all diseases together. The difference between male and females was significant at baseline for all 3 TNFi; whereas with the use of ETA the significant difference was carried through to V2 and V3, it was lost with the use of IFX and was variable with the other TNFi (Fig.1b)Figure 1.Conclusion:Female patients showed a statistically lower response to TNFi in all three disease entities (RA, SpA and PsoA) to a variable degree in our homogenous central european population. Interestingly, the difference was not uniform across individual TNFi when measured by HAQ. Gender differences were also seen in response to Apremilast.Disclosure of Interests:Elisabeth Loibner: None declared, Valentin Ritschl: None declared, Burkhard Leeb Speakers bureau: AbbVie, Roche, MSD, Pfizer, Actiopharm, Boehringer-Ingelheim, Kwizda, Celgene, Sandoz, Grünenthal, Eli-Lilly, Grant/research support from: TRB, Roche, Consultancies: AbbVie, Amgen, Roche, MSD, Pfizer, Celgene, Grünenthal, Kwizda, Eli-Lilly, Novartis, Sandoz;, Peter Spellitz: None declared, Gabriela Eichbauer-Sturm: None declared, Jochen Zwerina: None declared, Manfred Herold: None declared, Miriam Stetter: None declared, Rudolf Puchner Speakers bureau: AbbVie, BMS, Janssen, Kwizda, MSD, Pfizer, Celgene, Grünenthal, Eli-Lilly, Consultant of: AbbVie, Amgen, Pfizer, Celgene, Grünenthal, Eli-Lilly, Franz Singer: None declared, Ruth Fritsch-Stork: None declared

Abstract 481: Deactivation of the renin-angiotensin-aldosterone system (RAAS) lowers glycated Hemoglobin (HbA1c) in hypertensive patients with Atherosclerotic Renal Artery Stenosis (ARAS)

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Paola Caielli ◽  
Viola Sanga ◽  
Raffaella Motta ◽  
Michele Battistel ◽  
Lorenzo Calò ◽  
...  
Keyword(s):  
Glycemic Control ◽  
Medical Therapy ◽  
Randomized Clinical Trials ◽  
Optimal Medical Therapy ◽  
Causative Role ◽  
Atherosclerotic Renal Artery Stenosis ◽  
Contralateral Kidney ◽  
Significant Difference ◽  
The Difference

Background: blockade of the RAAS lowered the incidence of Diabetes Mellitus in randomized clinical trials, but whether the de-activation of the RAAS can elicit the same beneficial effect in patients with renovascular hypertension (RVH) is unknown. Aim: to verify if endovascular treatment (EVT) could improve glycemic control in patients with atherosclerotic RVH. Methods: in the METRAS study (http://clinicaltrials.gov/show/NCT01208714, a randomized clinical trial comparing the effect of EVT on top of optimal medical therapy versus medical therapy alone (OMT) on GFR of the ischemic and contralateral kidney in patients with atherosclerotic RVH), glycemic control, as assessed by HbA1c at baseline and repeatedly during follow-up, was a pre-specified secondary endpoint of the study. Results: between June 2010 and March 2014, 16 patients were randomly assigned to EVT plus optimal medical therapy (n = 9) or OMT alone (n = 7). At baseline the 2 groups showed no significant difference of age, clinical and demographical features. All the patients, except two in the EVT group, were on a RAAS blocker. At 2 years follow-up HbA1c increased in patients on OMT (59±12 mmol/mol) from baseline values (45±16 mmol/mol, p<0.001). By contrast, in the patients assigned to EVT HbA1c remained stable (42±7 mmol/mol at baseline vs 41±5 mmol/mol at follow-up; p = NS; p<0.001 vs OMT at follow-up). When analyzed after multivariate adjustment for age, HbA1c at enrollment, and presence/absence of DM, the difference between the arms remained highly significant (p<0.001). Conclusions: in patients with atherosclerotic RVH and chronic activation of the RAAS, deactivation of the RAAS by means of EVT was associated with no increase in plasma levels of HbA1c over long term follow-up. At variance, similar patients assigned to optimized medical therapy alone showed worsened glycemic control over time. These findings support the contention of a causative role of RAAS activation in the incidence/progression of DM.

scholarly journals A comparative study of functional outcome between platelet rich plasma injection versus steroid infiltration in plantar fasciitis

2020 ◽  
Vol 6 (2) ◽  
pp. 393
Author(s):  
Harpreet Singh ◽  
Malay P. Gandhi ◽  
Aliasgar J. Rampurwala ◽  
Tej S. Rudani
Keyword(s):  
Comparative Study ◽  
Plantar Fasciitis ◽  
Platelet Rich Plasma ◽  
Corticosteroid Injection ◽  
Injection Group ◽  
Plasma Injection ◽  
Significant Difference ◽  
The Difference ◽  
The Individual

<p class="abstract"><strong>Background:</strong> Plantar fasciitis (PF) is considered as degenerative tendinopathies. Repeated micro trauma is the major etiology of these diseases. Autologous platelet rich plasma (PRP) injections are becoming more popular in the treatment of enthesopathies like PF. The growth factors in PRP cause tissue healing. We compared the result of injecting intra-lesional autologous PRP injections versus steroid infiltration in chronic PF.</p><p class="abstract"><strong>Methods:</strong> A prospective, interventional and analytic comparative study was done and 81 patients (120 heels) were included in this study and were followed up for 6 months. We assessed the outcome of each patient using visual analog score (VAS) and foot and ankle disability index (FADI) on follow-up at 1, 3, and 6 months. <strong></strong></p><p class="abstract"><strong>Results:</strong> In our study, female preponderance was seen. Left side was more common as compared to right side. Unilateral PF is more common than bilateral. The difference with in the individual group at baseline and at 1,3 and 6 months was statistically highly significant in terms of VAS and FADI (p=0.0001) But the difference in the between the two groups was insignificant for VAS and FADI at 1, 3 and 6 months.</p><p class="abstract"><strong>Conclusions:</strong> In our study, as there is no significant difference in VAS and FADI score between corticosteroid injection group and PRP injection group at 1, 3 and 6 months follow up. So, it’s reasonable to conclude that both are equally effective in PF. But as PRP injection comes out to be more time consuming and more costly, corticosteroid seems to be more efficient, cost and time wise. Hence, the latter should be a better choice.      </p>

Effects of Orthokeratology Lens On Axial Length Elongation in Myopia With Anisometropia Children

2021 ◽  
Author(s):  
Ziyang Chen ◽  
Kai-Ming Chen ◽  
Ying Shi ◽  
Zhao-Da Ye ◽  
Sheng Chen ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Axial Length ◽  
Statistical Significance ◽  
Spherical Equivalent ◽  
Significant Difference ◽  
The Mean ◽  
The Difference ◽  
Better Than ◽  
Group 1

Abstract AimTo investigate the effect of orthokeratology (OK) lens on axial length (AL) elongation in myopia with anisometropia children.MethodsThirty-seven unilateral myopia (group 1) and fifty-nine bilateral myopia with anisometropia children were involved in this 1-year retrospective study. And bilateral myopia with anisometropia children were divided into group 2A (diopter of the lower SER eye under − 2.00D) and group 2B(diopter of the lower SER eye is equal or greater than − 2.00D). The change in AL were observed.The datas were analysed using SPSS 21.0.Results(1) In group 1, the mean baseline AL of the H eyes and L eye were 24.70 ± 0.89 mm and 23.55 ± 0.69 mm, respectively. In group 2A, the mean baseline AL of the H eyes and L eyes were 24.61 ± 0.84 mm and 24.00 ± 0.70 mm respectively. In group 2B, the mean baseline AL of the H eyes and L eyes were 25.28 ± 0.72 mm and 24.70 ± 0.74 mm. After 1 year, the change in AL of the L eyes was faster than the H eyes in group 1 and group 2A (all P<0.001).While the AL of the H eyes and L eyes had the same increased rate in group 2B. (2) The effect of controlling AL elongation of H eyes is consistent in three groups (P = 0.559).The effect of controlling AL elongation of L eyes in group 2B was better than that in group 1 and group 2A (P < 0.001). And the difference between group 1 and group 2A has no statistical significance. (3) The AL difference in H eyes and L eyes decreased from baseline 1.16 ± 0.55mm to 0.88 ± 0.68mm after 1 year in group 1.And in group 2A, the AL difference in H eyes and L eyes decreased from baseline 0.61 ± 0.34mm to 0.48 ± 0.28mm. There was statistically significant difference (all P<0.001). In group 2B, the baseline AL difference in H eyes and L eyes has no significant difference from that after 1 year (P = 0.069).ConclusionsMonocular OK lens is effective on suppression AL growth of the myopic eyes and reduce anisometropia value in unilateral myopic children. Binocular OK lenses only reduce anisometropia with the diopter of the low eye under − 2.00D. Binocular OK lenses cannot reduce anisometropia with the diopter of the low eye equal or greater than − 2.00D. Whether OK lens can reduce refractive anisometropia value is related to the spherical equivalent refractive of low refractive eye in bilateral myopia with anisometropia children after 1-year follow-up.

Is Subacromial Balloon Spacer Appropriate for Treatment of Irreparable Rotator Cuff Tears in Elderly Patients?

2019 ◽  
Vol 21 (6) ◽  
pp. 417-426
Author(s):  
Kamil Yamak ◽  
Hüseyin Gökhan Karahan ◽  
Taşkın Altay ◽  
Cemil Kayalı ◽  
Fırat Ozan
Keyword(s):  
Rotator Cuff ◽  
Rotator Cuff Tears ◽  
Dash Score ◽  
X Rays ◽  
Preoperative Period ◽  
Subacromial Space ◽  
Significant Difference ◽  
The Difference ◽  
Quick Dash

Background. The aim of this study was to evaluate the clinical and radiographic results of surgical treatment of irreparable rotator cuff tears by subacromial balloon spacer insertion in patients over 65 years old. Material and methods. Results of patients with failed conservative treatment for irreparable rotator cuff tears and who underwent subacromial balloon spacer insertion were evaluated retrospectively. The VAS and Quick-DASH scores were used for clinical and functional assessment. Results. Eleven patients were included. Mean age of patients was 69.1 (range: 65-77) years old. Evaluation of anteroposterior shoulder x-rays revealed Hamada grade 2 and grade 1 arthropathy in 10 patients (91%) and 1 patient (9%),respectively. Mean duration of follow-up was 45.09 (±5.43,37-52) months. The difference in the subacromial space measured from standard AP shoulder x-rays in the preoperative period, in the 6th postoperative month, and at the end of follow-up was 5.44 mm (2.29), 6.51 mm (±2.23), and 5.08 mm (±2.13), respectively. Mean Quick-DASH score was 74.49(±14.36) in the preoperative period, compared to 72.19 (±14.38) at the end of follow-up. There was no statistically significant difference between preoperative period and end of follow-up scores in terms of mean Quick-DASH scores (p= 0.232). Mean VAS score was 7.09 (±0.831) in the preoperative period and 6.64 (±0.809) at the end of follow-up. No statistically significant difference was revealed in terms of mean VAS scores when preoperative and end of follow-up scores were compared (p=0.333). Conclusion. Clinical and radiographic results of subacromial balloon spacer insertion in the treatment of irreparable rotator cuff tears could not be evaluated as satisfactory.

A comparative study on treatment outcomes of bandage and casting in non-displaced extra-articular fracture of distal radius: A clinical trial study

2020 ◽  
Vol 92 (5) ◽  
pp. 1-5
Author(s):  
Hamid Reza Arti ◽  
Reza farahnak
Keyword(s):  
Clinical Trial ◽  
Distal Radius ◽  
Dash Score ◽  
Articular Fracture ◽  
Appropriate Treatment ◽  
Significant Difference ◽  
Vas Scores ◽  
The Difference ◽  
Fracture Of Distal Radius

Background: There are some therapeutic choices in non-displaced extra-articular fracture of distal radius that confront with some controversy in their selection. We tried to study these two methods in this article. Methods: This was a prospective randomized clinical trial conducted on the patients (n=62) with NDEA fracture of distal radius, during 2015. The patients were randomly assigned to casting (n-32) or bandage (n=30) group to receive the respective fracture healing procedure. The patients were followed-up at the first, second, third, and sixth weeks after the treatment. The Disabilities of the DASH and the VAS questionnaire were completed. All patients underwent an X-ray radiographic assessment to evaluate any potential complication. Results: At the end of the study, in the bandage and casting group 30 and 32 patients finished the study. The statistical analyses showed that the bandage group showed significantly higher mean DASH score than the casting group at the first week, but for the second week the difference decreased so that for the third week, the casting group showed significantly higher value than the bandage group. Finally, at the sixth week the two groups showed no significant difference in the DASH value. The two groups showed no significant differences in the VAS scores for all follow up assessments. The returning time to work was shorter in the bandage group and the treatment cost was also lower in this group. Conclusion: Bandage is more appropriate treatment option for the NDEA fractures of distal radius.

The Role of Multidrug Resistance Proteins and Drug Sensitivity in Relation to Poor Prognosis Identified by ZAP-70 Expression and IgVH Mutation Status in B-CLL.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4791-4791
Author(s):  
S. Narat ◽  
N. I. Folarin ◽  
R. J. Baker ◽  
V. Duke ◽  
B. C. Yogashangary ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Multidrug Resistance ◽  
Functional Activity ◽  
Poor Prognosis ◽  
Drug Sensitivity ◽  
Good Prognosis ◽  
Cytotoxic Drugs ◽  
Resistance Proteins ◽  
Significant Difference

Abstract A proportion of haematological malignancies over express the multidrug resistance (MDR) efflux proteins - P-glycoprotein (P-gp), multidrug resistance protein (MRP1) and lung resistance proteins (LRP) that confer resistance to a number of structurally unrelated cytotoxic drugs. The clinical significance of the observed over expression of P-gp in B-CLL regardless of stage or treatment of the disease is unclear, although a protective effect on cell survival has been reported. Recent evidence suggest that a sub-group of B-CLL exist with an aggressive clinical course that is often resistant to treatment. B-CLL cells from this subgroup of patients have unmutated immunoglobulin heavy chain variable region (IgVH) and express zeta-associated protein (ZAP-70). We analysed the association between the expression of MDR proteins and the prognosis indicator ZAP-70 in cells from 46 B-CLL patients (30M/16F, 33 stage A, 7 B, 6 C) for (i) ZAP-70 expression using an antibody (clone 2F3.2)-Alexa Fluor 488 conjugate by flow cytometry and expressed as a ratio of B to T-cell mean cell fluorescence, (ii) the expression of P-gp, MRP1 and LRP protein by flow cytometry using specific antibodies and expressed as MCF ratio to isotype controls, (iii) flow cytometric analysis of functional activity of P-gp expressed as MCF ratio in the presence and absence of verapamil, a known inhibitor of P-gp, (iv) IC50 (μg/ml) for cytotoxic drugs 2-chlorodeoxyadenosine (CdA), chlorambucil (Chl) and fludarabine (FdR) using the cytotoxicity MTT assay and (v) IgVH mutational status by sequence analysis of FR1/JH polymerase chain reaction products in 29/46 (63%) of patients. 13/46 (28%) patients were ZAP-70+ve and the remaining 33/46 (72%) were ZAP-70−ve. P-gp expression (median 1.59 in both groups p=0.85) and P-gp functional activity (median 2.01 vs 1.84 p=0.77) were not statistically different between ZAP-70+ve and ZAP-70−ve groups. There was no significant difference in the expressions of MRP1 (median 2.77 vs 3.48 p=0.31) or LRP (median 4.87 vs 5.18 p=0.56) between ZAP-70+ve and ZAP-70−ve patients. The IC50 levels for CdA, Chl and FdR between ZAP+ve (median 0.04, 6.4 & 0.54mg/ml respectively) and ZAP−ve groups (median 0.065, 12.15 & 0.72 respectively) were not statistically significant (p=0.67, 0.45, 0.36 respectively). 9 ZAP-70+ve and 15 ZAP-70−ve patients were sequentially investigated over a median period of 3 years for expression of P-gp, MRP1, LRP and P-gp function. There were no significant changes in P-gp expression and P-gp function between presentation and follow samples over this period. However, a significant increase in expression of MRP1 (median at presentation 1.65 and follow up 5.23 p= 0.0001) and LRP (median at presentation 3.92 and follow up 5.84 p= 0.0002 respectively) were observed for the ZAP-70−ve group. IgVH mutation analysis was concordant with ZAP-70 expression in 6 patients with poor prognosis (ZAP-70+ve/IgVH unmutated) and in 16 with good prognosis (ZAP-70−ve/IgVH mutated). Statistical analysis of MDR protein expression and IC50 in this smaller cohort of patients provided data similar to that in the main group. MDR proteins, their activity and in vitro drug sensitivity appear not to significantly contribute to the poor prognosis subset of B-CLL identified by their ZAP-70+ve/IgVH unmutated status. The significance of increased MRP1 and LRP expression in the good prognosis ZAP−ve group is unclear.

Treatment of adenocortical carcinoma: 11-year Birmingham experience.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 462-462
Author(s):  
Lenka Zvirinska ◽  
Alice Tew ◽  
Emilio Porfiri
Keyword(s):  
Survival Data ◽  
Standard Treatment ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Limited Efficacy ◽  
Significant Difference ◽  
Unselected Population ◽  
Group 3 ◽  
Time To Relapse

462 Background: Due to the lack of prospective randomized phase III trial data, we have analysed patients with ACC treated between 2000 and 2011. Methods: All the patients given Mitotane (standard treatment of ACC in UHB, Birmingham) where extracted from pharmacy database. Results: 23 patients were identified, age 26-74 (median 53). Follow-up for whole group was 14–167m, median 60. Overall survival (OS) was 3-48m, medium 11.1 patient with slowly growing disease is still alive (167m) with 2nd dg of breast cancer. 19 patients were treated for metastatic disease, 4 in adjuvant setting. 7 patients were managed by endocrinologist only (3 adjuvant, 2 poor PS, 1 reluctant to treatment and 1 details unknown). 16 patients were under shared care. 4 these patients were never exposed to chemotherapy (2 poor PS, 1 returned to Africa, died within 5 months, 1 declined chemotherapy, still alive at 16 months post). 6/19 metastatic patients had chemotherapy as 1st treatment (4 patients etoposide/doxorubicin/cisplatin chemotherapy, 1 etoposide/carboplatin, 1 etoposide/cisplatin), 7 were treated with chemotherapy on PD(6 streptozocin, 1 etoposide/doxorubicin/cisplatin, 1 etoposide/cisplatin). There was no significant difference in OS when those approaches were compared (1st group 7-16 m, median 10, 2nd group 3-14, median 11) But TTP has been slightly worse for treatment on PD as expected (1st group 3-13m, median 6.5; 2nd group 3-14, median 3), although might be due to tendency to use Streptozocin, consistant with preliminary published results of FIRMACT trial.3 patients were treated with 2 lines of chemotherapy (age 30,31, 38), TTP 2- 5 m. Adjuvant patients within our sample has been followed up for limited perion only (11 – 71m, median 22.5), however no recurrence was diagnosed so far.In metastatic patient population 4 patients were treated for recurrence with time to relapse 3-43m, medium 23.5. Conclusions: ACC is heterogenic disease as confirmed by our survival data. In unselected population median OS is comparable to FIRMACT. Consistant with literature review, chemotherapy threatment can be delivered as 1st-line or delayed till PD. 2nd-line chemotherapy is of limited efficacy.

Evaluation of survival by ADCC status: Subgroup analysis of SB3 (Trastuzumab Biosimilar) and reference trastuzumab in patients with HER2-positive early breast cancer at three-year follow-up.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 580-580 ◽  
Author(s):  
Xavier Pivot ◽  
Mark D. Pegram ◽  
Javier Cortes ◽  
Diana Lüftner ◽  
Gary H. Lyman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Statistical Significance ◽  
Phase Iii ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Follow Up Study ◽  
Significant Difference ◽  
The Difference

580 Background: SB3 is an approved biosimilar of reference trastuzumab (TRZ). At additional 2-year follow-up after completing neoadjuvant and adjuvant treatment, there was a difference in event-free survival (EFS), but no difference in overall survival (OS) between SB3 and TRZ. Upon monitoring quality attributes of TRZ, a marked downward shift in antibody-dependent cell-mediated cytotoxicity activities (ADCC) was observed in TRZ lots with expiry dates from Aug 2018 to Dec 2019. Some of the lots were used in the Phase III study. This is a post-hoc analysis of EFS and OS by ADCC status from a 3-year follow-up to investigate the difference in EFS between SB3 and TRZ. Methods: After completion of neoadjuvant and adjuvant therapy in patients with HER2 positive early breast cancer, patients from selected countries participated in a 5-year follow-up study (NCT02771795). Within the TRZ group, patients exposed to at least one shifted ADCC lot and those never exposed to shifted ADCC lot during neoadjuvant period were considered as “Exposed” and “Unexposed,” respectively. EFS and OS after 3-year follow-up was analyzed by ADCC status in the long-term follow-up set. Results: 367 patients (SB3, N = 186; TRZ, N = 181) were enrolled in the follow-up study. Within TRZ, 55 patients were Unexposed and 126 patients were Exposed. At a median follow-up duration of 40.8 months in SB3 and 40.5 months in TRZ, 3-year EFS rates were 92.5% in SB3, 94.5% in Unexposed, and 82.5% in Exposed and OS rates were 97.0%, 100%, and 90.6%, respectively. Exposed was associated with decreased EFS compared to Unexposed (HR 0.14, 95% CI 0.04-0.51, p= 0.003). There was a trend of decreased OS in Exposed compared to Unexposed, however, there was no significant difference (HR 0.14, 95% CI 0.02-1.15, p= 0.068). Between SB3 and Unexposed, no difference was observed in EFS (HR 1.06, 95% CI 0.33-3.44, p= 0.923), or OS (HR 0.54, 95% CI 0.05-5.44, p= 0.600). Conclusions: Within the TRZ group, Exposed showed significantly lower EFS compared to Unexposed, and a similar trend was observed in OS with no statistical significance. Between SB3 and Unexposed, no significant difference in EFS or OS was observed. Clinical trial information: NCT02771795.

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